7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

11

Comparative study between cardioprotective effects

of intermittent antegrade blood cardioplegia with

terminal warm blood reperfusion (hot-shot) versus

intermittent antegrade blood cardioplegia in

pediatric cardiac surgery

Hussein H Sabri FRCA Samia I Sharaf MD Abla A Saab MD

Mohammed Saleh MSc

Department of Anesthesiology Intensive Care and Pain Management

Faculty of Medicine Ain shams University Cairo

Abstract

Background Terminal warm blood cardioplegia (hot-shot) has been shown to enhance

myocardial protection in adult cardiac surgery The aim of current study is to evaluateterminal warm cardioplegic blood reperfusion compared to conventional reperfusion to

determine whether it has a beneficial cardioprotective effect during pediatric cardiac

surgery Methods This prospective study was carried out in Ain Shams University

Hospital on sixty children scheduled for pediatric cardiac surgery Patients were

randomly allocated into 2 equal groups Control group (C) 30 patients received

intermittent antegrade cold blood cardioplegia Hot-shot group (HS) 30 patients

received intermittent antegrade cold blood cardioplegia with terminal warm blood

reperfusion just before declamping We traced and compared the effect of warm

cardioplegic blood reperfusion versus conventional reperfusion on clinical outcome

parameters myocardial oxygen and lactate extraction ratio after declamping and serum

level of cardiac troponin I Results This study demonstrated higher percentage of

spontaneous defibrillation into sinus rhythm in hot-shot group when compared to

control group (767 versus 333 respectively) lower level of inotropic support

required for weaning from CBP in hot-shot group when compared to control group

(44plusmn55 versus 105plusmn65 respectively) lower level of inotropic support required in the

ICU in hot-shot group when compared to control group ( 754plusmn612 versus 1225plusmn1032

respectively) less duration of inotropic support required in the ICU in hot-shot group

when compared to control group (95plusmn72 hours versus 149plusmn118 hours respectively)

Myocardial lactate extraction ratio was significantly elevated at all studied time

interval in hot-shot group when compared to control group lower level of Serum

troponin I at 4 hours after declamping in -shot group when compared to control group

(132plusmn80 ngml versus 313plusmn231 ngml) lower level of Serum troponin I at 8 hours

after declamping in hot-shot group when compared to control group (100 plusmn 58ngml

versus 191plusmn 115ngml) Conclusions This study demonstrated that intermittent cold

blood cardioplegia with terminal warm blood cardioplegia offered favorable effect on theclinical outcome parameters in term of higher percentage of spontaneous defibrillation

into sinus rhythm and lower level of inotropic support in comparison to intermittent

cold blood cardioplegia Moreover intermittent cold blood cardioplegia with terminal

warm blood cardioplegia accelerated recovery of aerobic metabolism and reduced the

myocardial damage following ischemia reperfusion injury

Keywords terminal warm blood cardioplegia bullHot-shot bull pediatric myocardialpreservation

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Comparison of cardioprotective effects Hussein Sabri et al

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Introduction

In an era when essentially nocongenital heart defect is consideredinoperable Repair of congenital

heart defects is becoming morefrequent in neonates and infantsThus pediatric myocardial pro-

tection has become of great interestto cardiac anesthetists who should

tailor their myocardial protectivetechniques to protect the immaturemyocardium during global myo-cardial ischemia to permit a greater

safety in performing complex con-genital heart repairs

Despite major advances in the

technical aspects of surgical repairof congenital heart diseases peri-

operative myocardial damage withlow cardiac output remains themost common cause of morbidityand death after repair of congenitallesion (Allen 2004) Cardiac

damage from inadequate myo-cardial protection can prolong

hospital stay and result in delayedmyocardial fibrosis leading to

cardiac dysfunction months to years

later So optimal myocardialprotection is as important as anexcellent technical repair inachieving the best long-term

outcome with surgical correction

Advances in cardioplegic techni-ques include intermittent ante-

grade cold blood cardioplegia withterminal warm blood reperfusion(hot-shot) that has been shown toenhance myocardial protection inadult cardiac surgery (Teoh et al

1986 Caputo et al 1998)

However because of structuralfunctional and biochemical diff-

erence in myocardial metabolismand response to ischemia andreperfusion cardioprotective stra-tegies should not be extrapolated to

pediatric cardiac practice withoutevident base (Toyoda et al 2003

Modi et al 2004)

The aim of the current study is

to evaluate the cardioprotectiveeffects of intermittent antegradecold blood cardioplegia withterminal warm blood cardioplegicreperfusion in pediatric cardiac

practice in comparison to inter-

mittent antegrade cold bloodcardioplegia

Patients and methods

After approval of both depart-ment of anesthesia faculty ofmedicine Ain Shams Universityand the medical ethics committeean informed consent was obtained

from the parents of each child

Methodology

Sixty children scheduled forpediatric cardiac surgery in AinShams University Hospital were

enrolled into this prospectiverandomized study Patients wererandomly allocated into two equalgroups Control group (C)

thirty patients submitted forcorrection of congenital heartdisease and received intermittent

antegrade cold blood cardioplegia

Study group [Hot-shot]

(HS) thirty patients submittedfor correction of congenital heartdisease and received intermittent

antegrade cold blood cardioplegia

with terminal warm cardioplegic

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

13

blood reperfusion just beforedeclamping of the aorta

The study population wasstratified based on clinical

diagnosis patients with right toleft shunt visualized by echo-cardiography were considered

cyanotic others considered non-cyanotic

Inclusion criteria Patients ofboth sexes presented for electiverepair of congenital heart diseaseBody weight 10-25kg Age12month-36month Exclusion

criteria Patients underwentpalliative operation (eg shuntpulmonary artery banding) andpresented for total repair Patientsunderwent previous repair andpresented for redo operationPatients on preoperative inotropicsupport Patients on preoperativemechanical ventilation

Anesthetic management Anesthetic technique was stan-

dardized for all patients Childrenshould have no milk formula orsolids for 6hrs prior to surgeryClear liquids are allowed up to 3hours preoperatively

Preoperative assessment After careful history taking a tho-rough physical examination wasdone This included assessment ofthe general condition chest exami-nation and measurement of axi-llary temperature Laboratorystudies chest x-ray and results ofechocardiography and catheteri-zation studies were reviewed

Premedication Patients were

premedicated with oral midazolamat a dose of 05mgkg-1 given 15min

before induction of anesthesia tofacilitate quiet separation from theparents

Induction of anesthesia

Anesthesia was induced withinhalation of halothane 2-3 in100 oxygen by face mask till a

peripheral venous cannula was

inserted and secured Then ane-sthesia was completed throughfentanyl 2microgkg-1 IV Trachealintubation was facilitated withpancuronium 01mgkg-1 IV

Ventilation was mechanically

controlled by Ohmeda 7800 venti-lator to deliver tidal volume of

10mlkg-1 respiratory rate wasadjusted achieve a partial pre-

ssure of carbon dioxide [PaCO2] of32-36mmHg

Monitoring On arrival to

operative theater patients were

monitored by electrocardiogram(lead II) pulse oximetry and non

invasive blood pressure Immed-iately after anesthetic inductionleft radial arterial catheter was

inserted after modified Allenstest for invasive blood pressuremonitoring and arterial bloodsampling Right internal jugular

triple lumen venous catheter wasalso inserted for monitoring ofcentral venous pressure andinfusing inotropes crystalloids

blood plasma and other drugs

Oropharyngeal temperaturewas also monitored All previousparameters were monitored usinga modular monitor (Hewlett-Packard model 64s) Arterial

blood samples were taken for

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Comparison of cardioprotective effects Hussein Sabri et al

14

blood gas acid base andelectrolytes analysis to correctany change in the ventilationelectrolytes or acid base balance

of the patient Maintenance of anesthesia

Anesthesia was maintained by

isoflurane 02-04 in 50 oxygen

air mixture extra analgesia wasprovided by fentanyl 10microgkg-1 IVbefore sternotomy in incrementsPancuronium in a dose of002mgkg-1 IV was used as

increment for adequate muscle

relaxation Management of cardio-

pulmonary bypass Immediately

after anesthetic induction activatedclotting time (ACT) was measuredand used as a control Anti-coagulation was achieved byadministration of heparin sulphate

3mgkg-1 IV and adjusted tomaintain ACT more than 480seconds Priming of Cardiopul-monary bypass (CPB) circuit

consisted of ringer solution

manifold sodium bicarbonate andblood or plasma depending oninitial hematocrit CPB wasestablished between ascending

aortic and bicaval cannulation CPBwas instituted using non-pulsatileflow ranging between 100-150mlkg-1min-1 to maintain mean

arterial pressure between 40-60mmHg

At full flow of CBP mecha-nical ventilation was stopped and

the lungs remained collapsed atthe functional residual capacityModerate systemic hypothermiawas used [28degC-32degC] Alpha stat

strategy for pH management wasadopted Hematocrit was main-tained above 25

Protocol of myocardial pro-tection In control group (C) Myo-

cardial protection was achievedwith intermittent antegrade coldblood cardioplegia with topicalheart cooling in all patients

Cardioplegic solution of 20mLKg-1

of body weight was initially infusedinto the aortic root after applicationof aortic cross clamp to achieve

cardiac arrest with subsequent

doses every 20min Blood cardio-plegia was prepared by mixingoxygenated blood with hyper-kalemic crystalloid solution in 11ratio with sodium bicarbonate

added as buffer lidocaine as mem-brane stabilizer and cooled to 9degC

[Table 1] [Table 2]

In hot-shot group (HS) Cardio-

plegic regimen was the same withan additional 20mLKg-1 of body

weight of warm (35degC) bloodcardioplegia was infused into the

aortic root just before declamping ofthe aorta The composition ofterminal warm blood cardioplegiawas the same as the cold blood

cardioplegia other than tempera-ture

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

15

Table (1) Components added to crystalloid solution per liter

KCl 40 mmol L-1

NaHCO3 40 mmol L-1

Lidocaine 100 mg L-1

Table (2) Final composition of cardioplegia after mixing oxygenatedblood with hyperkalemic crystalloid solution in 11 ratio

pH 76

Hematocrit 17-22

K + 20 mmol L-1

Na+ 150 mmol L-1

Cl+ 150 mmol L-1

Ca2+ 2 mmol L-1

Osmolaritv 380 mOsm L-1

Weaning of cardiopul-

monary bypass After completion

of the surgical repair rewarming

was instituted Standard deairingmaneuvers were performed beforeremoval of the aortic cross-clamp

Ventricular distention during re-perfusion was avoided by regu-

lation of systemic venous return

and ventricular vent Electricaldefibrillation was applied to theheart if ventricular fibrillation

persisted Pacing the heart was

applied if there was second orthird degree heart block orintractable sinus bradycardia

Once optimal heart rate

electrolyte acid-base and tem-perature were achieved mechanicalventilation was resumed Afteroptimizing preload and afterload

CBP was gradually stopped If

systolic blood pressure was lowerthan 80 mm Hg despite centralvenous pressure above 10cm H2Odobutamine was our first choice

inotrope [dobutamine infusion

starting at a dose of 5-15microgkg-1 min-1] Epinephrine was our secondchoice when dobutamine alone was

ineffective [epinephrine infusionstarting at a dose of 50-250ngkg-1

min-1] Inotrope dose was titratedaccording to the hemodynamic andclinical state of the patient

At the end of bypass

protamine sulfate in a dose of15mg per 1mg heparin was usedto neutralize heparin effect The

chest was then closed in routine

fashion once meticulous hemos-tasis was achieved

Postoperative care Patient

admitted to pediatric cardiac sur-

gery intensive care unit Routinepostoperative management wasgiven to all patients Decision regar-ding ventilation and inotrope were

based on unit protocol hemody-

namic status and clinical judgment

Parameters of the study

Assessment of clinical outcomeIntraoperative and postoperative

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

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O2 content CS oxygen content incoronary sinus blood sample

Myocardial lactate extraction

ratio was calculated according to

the following equation

Myocardial lactate extractionrate ratio= [lactate A - lactate CS] x100lactate A

Lactate A serum lactate concen-tration in arterial blood sample

Lactate CS serum lactate concen-

tration in coronary sinus bloodsample

Serum level of cardiac

troponin I (cTnI) Two millilitersof blood sample collected fromeach patient after induction of

anesthesia and at 4 8hrs afterdeclamping of the aorta Bloodsamples were centrifuged and

stored at -20deg until the completionof the study when thawed once

and assays were performed by a

laboratory technician blinded tothe clinical status of the patientor their inclusion in the studySerum concentration of cardiac

troponin I was determined with acommercially available enzyme-linked immunosorbent assay

(ELISA) kits cTnI ELISA-DRG

international Inc

Principle of the test Sample

was allowed to react with themicrotiter coated with monoclonalanti troponin I antibody (solid

phase) Monoclonal anti troponinI-enzyme (horseradish peroxidase)conjugate solution was added

resulting in the troponin I molec-

ules being sandwiched between

the solid phase and enzyme-linked antibodies

A solution of tetramethyl-benzidine (TMB) reagent was added

and incubated for 20 minutesresulting in the development of ablue color The color development

was stopped with the addition of 1Nhydrochloric acid (HCl) changing

the color to yellow The concen-tration of troponin I was directlyproportional to the color intensity ofthe test sample Absorbance was

measured spectrophotometrically

using Dade Behring Inc BEPreg

IIIat wavelength 450nm

Statistical analysis

All data were prospectively

collected coded tabulated thensubjected to statistical analysisusing SPSSreg for Windows version150 software packages Numericalvariables were presented as mean

and standard deviation (SD) while

categorical variables were presen-ted as number of cases and percent

Between-groups comparisons of

numerical variables were performedwith unpaired student-t test whilethose of categorical variables wereperformed by Fisher exact test orChi-square test as appropriate For

all tests P-value of less than 005

was considered statistically signifi-

cantResults

Patientsrsquo characteristics and

intraoperative data The demog-

raphic data and patients pathology

were comparable in both studygroups as shown in (Table 3)

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Comparison of cardioprotective effects Hussein Sabri et al

18

Intraoperative variables were alsocomparable in both study groups asshown in (Table 3) There was nosignificant difference as regards

cardiopulmonary bypass time (P

value was 0621) aortic cross-clamptime (P value was 0916) lowestoropharyngeal temperature (Pvalue was 0749)

Table 3 Patientsrsquo characteristics and intraoperative dataControl group

No =30

Hot-shot group

No =30P value

Age (month) 175 plusmn 56 181 plusmn 57 0716

Sex (MF) 1416 1614 0797

Weight (Kg) 141 plusmn 38 148 plusmn 42 0481

Pathology (n)

Acyanotic 17 19 ASD 6 7

VSD 7 9

CAVSD 4 3

Cyanotic 13 11

TOF 7 6

DORV- PS 6 5

CBP (min) 643plusmn 259 679plusmn 288 0621

Ao Cx (min) 378plusmn 169 382plusmn 171 0916

Oropharyngeal temp (degC) 306 plusmn 22 307 plusmn 20 0749

Mean plusmn SD MF male female ratio n number of patients ASD atrial septal defect

VSD ventricular septal defect CAVSD complete atrioventricular septal defect TOFtetralogy of Fallot DORV- PS double outlet right ventricle with pulmonary stenosis

CPB cardiopulmonary bypass Ao Cx aortic crossclamp P value is significant whenP lt 005 unpaired t test for age weight CBP Ao Cx and oropharyngeal temp

Fisherrsquos exact test for sex Chi-square test for pathology

Parameters of the study

Clinical outcome parameters

Intraoperative parametersThere was a significant difference

between both study groups after

declamping of the aorta Spon-taneous defibrillation into sinusrhythm occurred in 23 patients ofhot-shot group versus 10 patients of

control group (P value was 0002)Electrical defibrillation was requi-red in 7 patients of hotshot groupversus 20 patients of control group

(P value was 0002) (Table 4)

As regards requirement ofpacing to wean from cardio-pulmonary bypass there was no

significant difference between bothstudy groups Pacing was requiredin 5 patients of hot-shot groupversus 7 patients of control group (P

value was 0748) (Table 4)

As regards intraoperative

inotropes there was a significantdifference between both studygroups as regards number of

patients who required inotropes

for weaning of cardiopulmonarybypass Inotropes were requiredin 14 patients of hot-shot group

versus 24 patients of control group

(P value was 0015) (Table 4)

There was also a significantdifference between both groups as

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

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regards inotropic score requiredfor weaning fromcardiopulmonary bypass Inotropescore was 44plusmn55 in hot-shot

group versus 105plusmn65 in controlgroup (P-value was lt0001)(Table 4)

Table 4 Intraoperative clinical outcome variablesControl

group

No =30

Hot-shot

group

No =30

P

value

Spontaneous defibrillation into sinusrhythm n ()

10 (333) 23 (767) 0002

Electrical defibrillation n () 20 (667) 7 (233) 0002

Requirement of pacing for weaning fromCBP n ()

7 (233) 5 (167) 0748

Requirement of intraoperative inotrope n

()24 (80) 14 (467) 0015

Inotrope score required for weaning from

CBP Mean plusmn SD 105plusmn

65 44plusmn

55 lt0001

n() Number (percentage) of patients Mean plusmnSD P-value is significant when Plt005 unpaired t

test for inotrope score P value is significant when P lt 005 Fisherrsquos exact test for spontaneous

defibrillation electrical defibrillation requirement of pacing and intraoperative inotrope

Postoperative parameters

There was a significant

difference between both studygroups as regards inotropes

required in the intensive careInotropes were required in 14

patients of hot-shot group versus24 patients of control group (Pvalue was 0015) Inotrope score

in the ICU was 754plusmn612 in hot-shot group versus 1225plusmn1032 incontrol group (P value was 0036)

Inotrope duration was 95plusmn72hrsin hot-shot group versus

149plusmn118hrs in control group (Pvalue was 0039) (Table 5)

As regards duration ofmechanical ventilation there was

no significant difference betweenboth study groups Duration ofmechanical ventilation was 67 plusmn 38

hrs in hot-shot group versus88plusmn44hrs in control group (Pvalue was 0053) (Table 5)

As regards duration of ICU

stay there was no significantdifference between both study

groups Duration of ICU stay was511plusmn188hrs in hot-shot groupversus 603plusmn231hrs in control

group (P-value was 0099) (Table

5)

There was no significantdifference between both study

groups as regards mortality Therewas no postoperative death in hot-shot group versus 3 postoperative

deaths in control group (P valuewas 0237) (Table 5)

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Comparison of cardioprotective effects Hussein Sabri et al

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Table 5 Postoperative clinical outcome parametersControl

group

No =30

Hot-shot

group

No =30

P

value

Requirement of postoperative inotrope n () 24 (80) 14 (467) 0015

Inotrope score in ICU Meanplusmn SD 1225plusmn1032 754plusmn612 0036

Inotrope duration (h) Mean plusmn SD 149plusmn118 95plusmn72 0039

Duration of mechanical ventilation (h) Mean plusmn SD 88plusmn 44 67plusmn 38 0053

Duration of ICU stay (h) Mean plusmn SD 603 plusmn 231 511plusmn 188 0099

Mortality n () 3 (10) 0 (0) 0237

n () Number (percentage) of patients Mean plusmnSD P-value is significant when Plt005

unpaired t-test for inotrope score in ICU inotrope duration duration of mechanical Ventilation and duration of ICU stay P-value is significant when Plt005 Fisherrsquos exact test

for requirement of postoperative inotrope and mortality

Myocardial oxygen and lactate

extraction ratio As regards myo-

cardial oxygen extraction ratiothere was no significant differencebetween hot-shot group and

control group at the different

studied time intervals throughout

the initial sixty minutes ofreperfusion (P-value was gt005)(Table 6 Fig 1)

Table 6 Myocardial oxygen extraction ratio (MO2 ER)

Time interval after declamping of the aorta

Control

group

No =30

Hot-shot

group

No =30

P

value

M O2 ER immediately after declamping 529plusmn 62 512 plusmn 66 0308

M O2 ER 15 min after declamping 505plusmn 58 494 plusmn 61 0477

M O2 ER 30 min after declamping 492plusmn 55 480 plusmn 58 0414

M O2 ER 45 min after declamping 485plusmn 52 472 plusmn 55 0351

M O2 ER 60 min after declamping 476plusmn 51 468 plusmn 53 0554Mean plusmnSD P value is significant when P lt 005 unpaired t-test

983091983088

983091983093

983092983088

983092983093

983093983088

983093983093

983094983088

983088 983149983145983150 983089983093 983149983145983150 983091983088 983149983145983150 983092983093 983149983145983150 983094983088 983149983145983150

983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137

983117 983161 983151 983139 983137 983154 983140 983145 983137

983148 983151 983160 983161 983143 983141 983150 983141 983160 983156 983154 983137 983139 983156 983145 983151 983150 983154 983137 983156 983145 983151 983077 983139983151983150983156983154983151983148 983143983154983151983157983152

983144983151983156983085983155983144983151983156 983143983154983151983157983152

Fig 1 Myocardial oxygen extraction ratio Data are presented as mean Error bars represent

95 confidence interval

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

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As regards myocardial lactateextraction ratio there was signi-ficant difference between hot-shotgroup and control group at the

different studied time intervals

throughout the initial sixtyminutes of reperfusion (P-valueswere 0027 0042 0024 lt0001lt0001 respectively) (Table 7

Fig 2)

Table 7 Myocardial lactate extraction ratio (M lactate ER)

Time interval after declamping of the aorta

Control

group

No =30

Hot-shot

group

No =30

P-

value

M lactate ER immediately after declamping -222plusmn 59 -190plusmn 50 0027

M lactate ER 15 min after declamping -136plusmn 50 -111plusmn 42 0042

M lactate ER 30 min after declamping -75plusmn 54 -44plusmn 49 0024

M lactate ER 45 min after declamping -48plusmn 40 00plusmn 46 lt0001

M lactate ER 60 min after declamping -26plusmn 34 59plusmn 41 lt0001

Mean plusmn SD P value is significant when Plt005 unpaired t-test

983085983091983088

983085983090983093

983085983090983088

983085983089983093

983085983089983088

983085983093

983088

983093

983089983088

983089983093

983090983088

983088 983149983145983150 983089983093 983149983145983150 983091983088 983149983145983150 983092983093 983149983145983150 983094983088 983149983145983150

983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137

983117 983161 983151 983139 983137 983154 983140 983145 983137 983148 983148 983137 983139 983156 983137 983156 983141 983141 983160 983156 983154 983137 983139 983156

983145 983151 983150 983154 983137 983156 983145 983151 983077

983139983151983150983156983154983151983148 983143983154983151983157983152

983144983151983156983085983155983144983151983156 983143983154983151983157983152

Fig 2 Myocardial lactate extraction ratio Data are presented as mean Error bars

represent 95 confidence interval P-value is significant when Plt005

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Comparison of cardioprotective effects Hussein Sabri et al

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Serum level of cardiac troponinI (cTnI) There was no significantdifference between both studygroups as regards baseline values of

serum troponin I (P-value was0146) There was significantdifference between both study

groups in serum troponin I level at4 and 8 hours after declamping of

the aorta Serum troponin I level at

4 hours after declamping was132plusmn80ngml in hot-shot groupversus 313plusmn231ngml in controlgroup (P value was lt0001) Serum

troponin I level at 8 hours afterdeclamping was 100plusmn58ngml inhot-shot group versus 191plusmn115ngml in control group (P value waslt0001) (Table 8 Fig 3)

Table 8 Serum level of cardiac troponin I (cTnI)Control

group

No =30

Hot-shot

group

No =30

P

value

Baseline (ngml) 08plusmn

04 07plusmn

04 01464 hrs after declamping of the aorta (ngml) 313plusmn 231 132 plusmn 80 lt0001

8 hrs after declamping of the aorta (ngml) 191plusmn 115 100 plusmn 58 lt0001

Mean plusmn SD P-value is significant when P lt 005 unpaired t test

983088

983093

983089983088

983089983093

983090983088

983090983093

983091983088

983091983093

983092983088

983092983093

983138983137983155983141983148983145983150983141 983092 983144983154983155 983096 983144983154983155

983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137

983124 983154 983151 983152 983151 983150 983145 983150 983113 983080 983150 983143 983087 983149 983148 983081

983139983151983150983156983154983151983148 983143983154983151983157983152

983144983151983156983085983155983144983151983156 983143983154983151983157983152

Fig 3 Serum level of cardiac troponin I (cTnI) Data are presented as mean Errorbars represent 95 confidence interval P value is significant when P lt 005

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

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Discussion

Low cardiac output aftersurgically induced ischemia andreperfusion continues to be a major

contributor to morbidity andmortality after pediatric cardiacsurgery and in more than 50 of

cases has been attributed toinadequate myocardial protection(Bull et al 1984 Hammon

1995)

Careful control of theconditions of reperfusion and the

composition of the reperfusate can

optimize postischemic recovery ofmyocardial function (Follette et

al 1981 Allen et al 1986)

The current study wasdesigned to evaluate the cardio-protective effect of using inter-mittent antegrade cold bloodcardioplegia versus intermittent

cold blood cardioplegia with ter-minal warm blood cardioplegia

(hot-shot) in pediatric cardiacpatients

The result of the current

study demonstrated significantdecrease in blood pressure at 5and 15 minutes interval in thecontrol group compared with the

hot-shot group after weaning ofthe cardiopulmonary bypass

Intermittent cold blood

cardioplegia with terminal warmblood cardioplegia offers favorable

effect on the clinical outcomeparameters This was demon-strated in this study as asignificant higher percentage ofspontaneous defibrillation into

sinus rhythm in hot-shot group

than control group (767 versus333 respectively)

The percentage of patientsrequiring inotropic support after

weaning from cardiopulmonarybypass was significantly higher incontrol group than hot-shot group

(80 versus 467 respectively)

By adopting the inotropic scoredescribed by Wernovsky et al

(1995) the level of inotropic

support was significantly lower inhot-shot group than control group

(44plusmn55 versus 105plusmn65 respec-

tively)

The improved clinical outcomerevealed the role of intermittent

cold blood cardioplegia withterminal warm blood cardioplegia inenhancement of myocardialprotection which was manifested asa reduction in myocardial arrhyth-

mia associated with ischemiareperfusion and a better myocardial

functionThe myocardial protective effect

of terminal warm blood cardioplegia

extended into the postoperativeperiod This was manifested as asignificant higher percentage ofpatients in control group than hot-

shot group who required inotropicsupport in the intensive care (80

versus 467 respectively) The

maximum dose of inotropic support(calculated by a modification of

inotropic score) was significantlyhigher in control group than hot-shot group (1225plusmn1032 versus754plusmn612 respectively) Theduration of inotropic support was

significantly higher in control group

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Comparison of cardioprotective effects Hussein Sabri et al

24

than hot-shot group (149plusmn118versus 95plusmn72 respectively)

In the postoperative periodresults were comparable as

regards duration of mechanicalventilation and stay in theintensive care unit in addition to

comparable mortality rate

Myocardial oxygen extraction

ratio reflects balance betweenmyocardial oxygen supply anddemand Myocardial oxygenextraction ratio was similar

between the two studied groups

This similarity may reflect theaerobic metabolic state of the

myocardium provided by the coldblood cardioplegia in both groups

Lactate release from theischemic myocytes is considered asa reflection of anaerobic metabolism(Krause et al 1993)

A negative myocardial lactateextraction ratio indicates that

amount of lactate productionthrough anaerobic glycolysis washigher than the amount of lactate

consumption for aerobic energy pro-duction with continuing anaerobicmetabolism and impairment ofnormal aerobic energy production

While a positive myocardial

lactate extraction ratio indicatesthat amount of lactate production

through anaerobic glycolysis wasless than the amount of lactate

consumption for aerobic energyproduction and that myocardiumstarts to use lactate as a substratevia oxidative phosphorylation

Myocardial lactate extractionratio in control group stayednegative value all through the sixtyminutes of studied period which

indicates impairment of aerobicmyocardial metabolism during thisperiod In hot-shot group myo-cardial lactate extraction ratioremained negative value till 45min

after declamping of the aorta when

it becomes a positive value

This point is considered a turnfrom anaerobic to aerobic meta-

bolism and it resembles the equilib-

rium between lactate consumptionand production At this point themyocardium starts to use lactate as

a substrate via oxidative phosphor-rylation (Krause et al 1993)

The results of this studydemonstrate the recovery of aerobicmetabolism afforded by inter-

mittent cold blood cardioplegia withterminal warm blood cardioplegiaTroponin I is a myocyte-contractileapparatus protein released follo-

wing myocardial damage Troponin

I Level is considered sensitivemarker of myocardial injuryassociated with cardiac surgery

(Immer et al 1998)

In this study we demonstrated

a significant increase in post-operative troponin I at 4 8 hoursafter declamping of the aorta in

control group compared to hot-shotgroup (P value was lt0001) Thisreflects the beneficial effect of warmcardioplegic reperfusion on myo-cardial outcome in reducing themyocardial damage following

ischemiareperfusion injury

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

25

In this study the composition ofterminal warm blood cardioplegiawas made to resemble the compo-sition of cold blood cardioplegia

used The point was to provide asolution with adequate potassiumconcentration to produce electro-mechanical arrest during reper-fusion This solution differs from the

conventional blood reperfusate in

presence of high potassiumconcentration (20mmolL-1) ahigher pH and a higher osmolarity

Thus cardioprotective effect ofterminal warm blood cardioplegia is

expected to be achieved byprolongation of electromechanicalarrest which reduces the energy

demands and counteracting tissueacidosis and edema therefore it

reduces the myocardial injury bypreservation and resynthesis ofhigh energy phosphates

There were small number ofclinical studies that have

examined specific myocardialprotection strategy in pediatric

population Utilizing an isolatedblood perfused neonatal heartpreparation Nomura et al

(2001) assessed the effects of

terminal warm blood cardioplegiaterminal warm oxygenated crys-talloid cardioplegia in comparisonwith conventional reperfusion(without any kind of terminal

cardioplegia) through assessmentrecovery of left ventricularfunction They demonstrated that

reperfusion with either terminalwarm blood cardioplegia or ter-

minal warm oxygenated crys-talloid cardioplegia resulted in

better recovery of myocardialfunction with slightly betterfunction in terminal warm bloodcardioplegia

In a clinically relevant intactanimal model that simulated theclinical condition of hypoxic

neonatal myocardium exposed toischemic stress Kronon et al

(2000) investigated the cardio-

protective effects of terminalwarm blood cardioplegic reper-fusion versus conventional reper-

fusion through assessment reco-

very of left ventricular systolicfunction and diastolic complianceThey showed that A warm cardio-

plegic reperfusion helps reduce

the reperfusion injury resultingin improved myocardial functionand metabolic recovery in hypoxicneonatal myocardium

Toyoda et al (2003) examined

the cardioprotective effect ofterminal warm blood cardioplegia inpediatric cardiac patients Blood

cardioplegia solution was composed

by mixing a hyperkalemic solutionwith oxygenated blood in 12dilutions with temperature 9oCThe terminal warm blood

cardioplegia had a finalconcentration of potassium 18mmolL-1 The results of Toyoda et alshowed beneficial effect of terminal

warm blood cardioplegia inreduction of myo-cardial injury Inagreement with Toyoda the

protocol of cardioplegiaadministered is almost similar asregard the concentration of pota-

ssium in terminal warm bloodcardioplegia (20mmolL-1) in 11

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Comparison of cardioprotective effects Hussein Sabri et al

26

dilution (1 crystalloid 1 blood) withsimilar result in myocardial pro-tection and improvement in aerobicenergy metabolism As a marker of

myocardial necrosis the currentstudy used troponin I whichprovides comparable information astroponin T used in the study ofToyoda

The current study is inagreement with Modi et al

(2004) who compared the use of

crystalloid cardioplegia cold blood

cardioplegia and cold blood

cardioplegia with hot-shot incyanotic and acyanotic pediatricpatients undergoing surgical

correction The efficacy of the 3

techniques was assessed byexamination right ventricularbiopsy specimen before and afterreperfusion analysis of cellular

metabolites and assessment oftroponin I level Their resultdemonstrated that for cyanotic

patients blood cardioplegia withhot-shot reduced metabolic injury

compared with cold crystalloidcardioplegia They also showed

that cold blood cardioplegia wason its own better than crystalloid

but not as good as cold bloodcardioplegia with hot-shot

Young et al (1997) failed to

demonstrate statistical advantage

for blood cardioplegia over crys-talloid cardioplegia in surgery forcongenital heart The most impor-

tant aspect of the study of Younget al is that no obvious benefitcan be anticipated by use of blood

cardioplegia in congenital heartsurgery when only antegrade

hypothermia dosing technique isused The integrated cardioplegicapproach using warm cold ante-grade and retrograde technique

with substrate enrichment may bebeneficial for pediatric population

As conclusion the result of

the current study showed that theuse of cardioplegia with hot-shot

provides the criteria that mayimprove myocardial protectionand reduce myocardial injury inpediatric population

These criteria include warm

blood accelerates recovery oftemperature-dependent enzymatic

and metabolic function highpotassium concentration prolongs

electromechanical arrest to decreaseenergy demands alkaloid solutionwhich counteracts tissue acidosisand high osmolarity which coun-teracts tissue edema

References

1 Allen BS Okamoto F

Buckberg GD Bugyi H

Young H Leaf J

Beyersdorf F Sjostrand F

and Maloney JV Jr

Studies of controlledreperfusion after ischemiaXV Immediate functional

recovery after six hours of

regional ischemia by careful

control of conditions ofreperfusion and compositionof reperfusate J Thorac

Cardiovasc Surg 1986 92(3Pt 2) 621-35

2 Allen BS Current Conceptsin Pediatric Myocardial

Protection In Salerno TA and

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

27

Ricci M (editors) MyocardialProtection 1st editionBlackwell publishing 2004207-29

3 Allen BS Pediatricmyocardial protection acardioplegic stra-tegy is the

solution Semin Thorac

Cardiovasc Surg Pediatr CardSurg Annu 2004 7 141-54

4 Bull C Cooper J and

Stark J Cardioplegicprotection of the childrsquos

heart J Thorac Cardio-vasc

Surg 1984 88(2) 287-93

5 Caputo M Dihmis WC

Bryan AJ Suleiman MS

and Angelini GD Warmblood hyperkalaemicreperfusion (hot shot)prevents myocardial substratederangement in patients

undergoing coronary arterybypass surgery Eur J

Cardiothorac Surg 199813(5) 559-64

6 Follette DM Fey K

Buckberg GD Helly JJ Jr

Steed DL Foglia RP and

Maloney JV Jr Reducingpostischemic damage by

temporary modifi-cation ofreperfusate calcium

potassium pH and

osmolarity J ThoracCardiovasc Surg 1981 82 (2)

221-38

7 Hammon JW Jr Myocardialprotection in the immatureheart Ann Thorac Surg 1995

60 (3) 839-842

8 Immer FF Stocker FP

Seiler AM Pfammatter JP

Printzen G and Carrel TP

Comparison of troponin-I and

troponin-T after pediatriccardiovascular opera-tion

Ann Thorac Surg 1998 66 (6)2073-7

9 Krause EG Pfeiffer D

Wollen-berger U and

Wollert HG Lactatemonitoring during and aftercardiopulmonary bypass an

approach implicating a peri-

operative measure for cardiacenergy metabolism In PiperHM Preusse CJ (editors)

Ischemia-reperfusion in

cardiac surgery 1st editionKluwer Academic 1993 317-33

10 Kronon MT Allen BS

Rahman S Wang T

Tayyab NA Bolling KS and

Ilbawi MN Reducingpostischemic reper-fusion

damage in neonates using a

terminal warm substrate-enriched blood cardioplegicreperfusate Ann Thorac Surg2000 70(3) 765-770

11 Modi P Suleiman MS

Reeves B Pawade A Parry

AJ Angelini GD and

Caputo M Myocardial

metabolic changes during ped-iatric cardiac surgery arando-mized study of 3cardioplegic techniques JThorac Cardiovasc Surg2004 128(1) 67-75

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Comparison of cardioprotective effects Hussein Sabri et al

28

12 Nomura F Forbess JM

and Mayer EJ Effects ofHot shot on recovery afterhypothermic ischemia in

neonatal lamb heart JCardiovasc Surg (Torino)2001 42(1) 1-7

13 Teoh KH Christakis GT

Weisel RD Fremes SE

Mickle DA Romaschin AD

Harding RS Ivanov J

Madonik MM Ross IM et

al Accelerated myocardial

metabolic recovery with

terminal warm bloodcardioplegia J ThoracCardiovasc Surg 1986 91(6)

888-95

14 Toyoda Y Yamaguchi M

Yoshimura N Oka S and

Okita Y Cardioprotectiveeffects and the mechanisms of

terminal warm bloodcardioplegia in pediatriccardiac surgery J ThoracCardiovasc Surg 2003 125

(6) 1242-51

15 Wernovsky G Wypij D

Jonas RA Mayer JE Jr

Hanley FL Hickey PR

Walsh AZ Chang AC

Castaneda AR NewburgerJW et al Postoperativecourse and hemodynamicprofile after the arterial

switch operation in neo-natesand infants A comparison of

low-flow cardiopulmonarybypass and circulatory arrestCirculation 1995 92(8) 2226-

35

16 Young JN Choy IO SilvaNK Obayashi DY and

Barkan HE Antegrade cold

blood cardioplegia is not

demonstrably advan-tageousover cold crystalloidcardioplegia in surgery forcongenital heart disease J

Thorac Cardiovasc Surg1997 114(6) 1002-9

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Comparison of cardioprotective effects Hussein Sabri et al

12

Introduction

In an era when essentially nocongenital heart defect is consideredinoperable Repair of congenital

heart defects is becoming morefrequent in neonates and infantsThus pediatric myocardial pro-

tection has become of great interestto cardiac anesthetists who should

tailor their myocardial protectivetechniques to protect the immaturemyocardium during global myo-cardial ischemia to permit a greater

safety in performing complex con-genital heart repairs

Despite major advances in the

technical aspects of surgical repairof congenital heart diseases peri-

operative myocardial damage withlow cardiac output remains themost common cause of morbidityand death after repair of congenitallesion (Allen 2004) Cardiac

damage from inadequate myo-cardial protection can prolong

hospital stay and result in delayedmyocardial fibrosis leading to

cardiac dysfunction months to years

later So optimal myocardialprotection is as important as anexcellent technical repair inachieving the best long-term

outcome with surgical correction

Advances in cardioplegic techni-ques include intermittent ante-

grade cold blood cardioplegia withterminal warm blood reperfusion(hot-shot) that has been shown toenhance myocardial protection inadult cardiac surgery (Teoh et al

1986 Caputo et al 1998)

However because of structuralfunctional and biochemical diff-

erence in myocardial metabolismand response to ischemia andreperfusion cardioprotective stra-tegies should not be extrapolated to

pediatric cardiac practice withoutevident base (Toyoda et al 2003

Modi et al 2004)

The aim of the current study is

to evaluate the cardioprotectiveeffects of intermittent antegradecold blood cardioplegia withterminal warm blood cardioplegicreperfusion in pediatric cardiac

practice in comparison to inter-

mittent antegrade cold bloodcardioplegia

Patients and methods

After approval of both depart-ment of anesthesia faculty ofmedicine Ain Shams Universityand the medical ethics committeean informed consent was obtained

from the parents of each child

Methodology

Sixty children scheduled forpediatric cardiac surgery in AinShams University Hospital were

enrolled into this prospectiverandomized study Patients wererandomly allocated into two equalgroups Control group (C)

thirty patients submitted forcorrection of congenital heartdisease and received intermittent

antegrade cold blood cardioplegia

Study group [Hot-shot]

(HS) thirty patients submittedfor correction of congenital heartdisease and received intermittent

antegrade cold blood cardioplegia

with terminal warm cardioplegic

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

13

blood reperfusion just beforedeclamping of the aorta

The study population wasstratified based on clinical

diagnosis patients with right toleft shunt visualized by echo-cardiography were considered

cyanotic others considered non-cyanotic

Inclusion criteria Patients ofboth sexes presented for electiverepair of congenital heart diseaseBody weight 10-25kg Age12month-36month Exclusion

criteria Patients underwentpalliative operation (eg shuntpulmonary artery banding) andpresented for total repair Patientsunderwent previous repair andpresented for redo operationPatients on preoperative inotropicsupport Patients on preoperativemechanical ventilation

Anesthetic management Anesthetic technique was stan-

dardized for all patients Childrenshould have no milk formula orsolids for 6hrs prior to surgeryClear liquids are allowed up to 3hours preoperatively

Preoperative assessment After careful history taking a tho-rough physical examination wasdone This included assessment ofthe general condition chest exami-nation and measurement of axi-llary temperature Laboratorystudies chest x-ray and results ofechocardiography and catheteri-zation studies were reviewed

Premedication Patients were

premedicated with oral midazolamat a dose of 05mgkg-1 given 15min

before induction of anesthesia tofacilitate quiet separation from theparents

Induction of anesthesia

Anesthesia was induced withinhalation of halothane 2-3 in100 oxygen by face mask till a

peripheral venous cannula was

inserted and secured Then ane-sthesia was completed throughfentanyl 2microgkg-1 IV Trachealintubation was facilitated withpancuronium 01mgkg-1 IV

Ventilation was mechanically

controlled by Ohmeda 7800 venti-lator to deliver tidal volume of

10mlkg-1 respiratory rate wasadjusted achieve a partial pre-

ssure of carbon dioxide [PaCO2] of32-36mmHg

Monitoring On arrival to

operative theater patients were

monitored by electrocardiogram(lead II) pulse oximetry and non

invasive blood pressure Immed-iately after anesthetic inductionleft radial arterial catheter was

inserted after modified Allenstest for invasive blood pressuremonitoring and arterial bloodsampling Right internal jugular

triple lumen venous catheter wasalso inserted for monitoring ofcentral venous pressure andinfusing inotropes crystalloids

blood plasma and other drugs

Oropharyngeal temperaturewas also monitored All previousparameters were monitored usinga modular monitor (Hewlett-Packard model 64s) Arterial

blood samples were taken for

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Comparison of cardioprotective effects Hussein Sabri et al

14

blood gas acid base andelectrolytes analysis to correctany change in the ventilationelectrolytes or acid base balance

of the patient Maintenance of anesthesia

Anesthesia was maintained by

isoflurane 02-04 in 50 oxygen

air mixture extra analgesia wasprovided by fentanyl 10microgkg-1 IVbefore sternotomy in incrementsPancuronium in a dose of002mgkg-1 IV was used as

increment for adequate muscle

relaxation Management of cardio-

pulmonary bypass Immediately

after anesthetic induction activatedclotting time (ACT) was measuredand used as a control Anti-coagulation was achieved byadministration of heparin sulphate

3mgkg-1 IV and adjusted tomaintain ACT more than 480seconds Priming of Cardiopul-monary bypass (CPB) circuit

consisted of ringer solution

manifold sodium bicarbonate andblood or plasma depending oninitial hematocrit CPB wasestablished between ascending

aortic and bicaval cannulation CPBwas instituted using non-pulsatileflow ranging between 100-150mlkg-1min-1 to maintain mean

arterial pressure between 40-60mmHg

At full flow of CBP mecha-nical ventilation was stopped and

the lungs remained collapsed atthe functional residual capacityModerate systemic hypothermiawas used [28degC-32degC] Alpha stat

strategy for pH management wasadopted Hematocrit was main-tained above 25

Protocol of myocardial pro-tection In control group (C) Myo-

cardial protection was achievedwith intermittent antegrade coldblood cardioplegia with topicalheart cooling in all patients

Cardioplegic solution of 20mLKg-1

of body weight was initially infusedinto the aortic root after applicationof aortic cross clamp to achieve

cardiac arrest with subsequent

doses every 20min Blood cardio-plegia was prepared by mixingoxygenated blood with hyper-kalemic crystalloid solution in 11ratio with sodium bicarbonate

added as buffer lidocaine as mem-brane stabilizer and cooled to 9degC

[Table 1] [Table 2]

In hot-shot group (HS) Cardio-

plegic regimen was the same withan additional 20mLKg-1 of body

weight of warm (35degC) bloodcardioplegia was infused into the

aortic root just before declamping ofthe aorta The composition ofterminal warm blood cardioplegiawas the same as the cold blood

cardioplegia other than tempera-ture

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

15

Table (1) Components added to crystalloid solution per liter

KCl 40 mmol L-1

NaHCO3 40 mmol L-1

Lidocaine 100 mg L-1

Table (2) Final composition of cardioplegia after mixing oxygenatedblood with hyperkalemic crystalloid solution in 11 ratio

pH 76

Hematocrit 17-22

K + 20 mmol L-1

Na+ 150 mmol L-1

Cl+ 150 mmol L-1

Ca2+ 2 mmol L-1

Osmolaritv 380 mOsm L-1

Weaning of cardiopul-

monary bypass After completion

of the surgical repair rewarming

was instituted Standard deairingmaneuvers were performed beforeremoval of the aortic cross-clamp

Ventricular distention during re-perfusion was avoided by regu-

lation of systemic venous return

and ventricular vent Electricaldefibrillation was applied to theheart if ventricular fibrillation

persisted Pacing the heart was

applied if there was second orthird degree heart block orintractable sinus bradycardia

Once optimal heart rate

electrolyte acid-base and tem-perature were achieved mechanicalventilation was resumed Afteroptimizing preload and afterload

CBP was gradually stopped If

systolic blood pressure was lowerthan 80 mm Hg despite centralvenous pressure above 10cm H2Odobutamine was our first choice

inotrope [dobutamine infusion

starting at a dose of 5-15microgkg-1 min-1] Epinephrine was our secondchoice when dobutamine alone was

ineffective [epinephrine infusionstarting at a dose of 50-250ngkg-1

min-1] Inotrope dose was titratedaccording to the hemodynamic andclinical state of the patient

At the end of bypass

protamine sulfate in a dose of15mg per 1mg heparin was usedto neutralize heparin effect The

chest was then closed in routine

fashion once meticulous hemos-tasis was achieved

Postoperative care Patient

admitted to pediatric cardiac sur-

gery intensive care unit Routinepostoperative management wasgiven to all patients Decision regar-ding ventilation and inotrope were

based on unit protocol hemody-

namic status and clinical judgment

Parameters of the study

Assessment of clinical outcomeIntraoperative and postoperative

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

17

O2 content CS oxygen content incoronary sinus blood sample

Myocardial lactate extraction

ratio was calculated according to

the following equation

Myocardial lactate extractionrate ratio= [lactate A - lactate CS] x100lactate A

Lactate A serum lactate concen-tration in arterial blood sample

Lactate CS serum lactate concen-

tration in coronary sinus bloodsample

Serum level of cardiac

troponin I (cTnI) Two millilitersof blood sample collected fromeach patient after induction of

anesthesia and at 4 8hrs afterdeclamping of the aorta Bloodsamples were centrifuged and

stored at -20deg until the completionof the study when thawed once

and assays were performed by a

laboratory technician blinded tothe clinical status of the patientor their inclusion in the studySerum concentration of cardiac

troponin I was determined with acommercially available enzyme-linked immunosorbent assay

(ELISA) kits cTnI ELISA-DRG

international Inc

Principle of the test Sample

was allowed to react with themicrotiter coated with monoclonalanti troponin I antibody (solid

phase) Monoclonal anti troponinI-enzyme (horseradish peroxidase)conjugate solution was added

resulting in the troponin I molec-

ules being sandwiched between

the solid phase and enzyme-linked antibodies

A solution of tetramethyl-benzidine (TMB) reagent was added

and incubated for 20 minutesresulting in the development of ablue color The color development

was stopped with the addition of 1Nhydrochloric acid (HCl) changing

the color to yellow The concen-tration of troponin I was directlyproportional to the color intensity ofthe test sample Absorbance was

measured spectrophotometrically

using Dade Behring Inc BEPreg

IIIat wavelength 450nm

Statistical analysis

All data were prospectively

collected coded tabulated thensubjected to statistical analysisusing SPSSreg for Windows version150 software packages Numericalvariables were presented as mean

and standard deviation (SD) while

categorical variables were presen-ted as number of cases and percent

Between-groups comparisons of

numerical variables were performedwith unpaired student-t test whilethose of categorical variables wereperformed by Fisher exact test orChi-square test as appropriate For

all tests P-value of less than 005

was considered statistically signifi-

cantResults

Patientsrsquo characteristics and

intraoperative data The demog-

raphic data and patients pathology

were comparable in both studygroups as shown in (Table 3)

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Comparison of cardioprotective effects Hussein Sabri et al

18

Intraoperative variables were alsocomparable in both study groups asshown in (Table 3) There was nosignificant difference as regards

cardiopulmonary bypass time (P

value was 0621) aortic cross-clamptime (P value was 0916) lowestoropharyngeal temperature (Pvalue was 0749)

Table 3 Patientsrsquo characteristics and intraoperative dataControl group

No =30

Hot-shot group

No =30P value

Age (month) 175 plusmn 56 181 plusmn 57 0716

Sex (MF) 1416 1614 0797

Weight (Kg) 141 plusmn 38 148 plusmn 42 0481

Pathology (n)

Acyanotic 17 19 ASD 6 7

VSD 7 9

CAVSD 4 3

Cyanotic 13 11

TOF 7 6

DORV- PS 6 5

CBP (min) 643plusmn 259 679plusmn 288 0621

Ao Cx (min) 378plusmn 169 382plusmn 171 0916

Oropharyngeal temp (degC) 306 plusmn 22 307 plusmn 20 0749

Mean plusmn SD MF male female ratio n number of patients ASD atrial septal defect

VSD ventricular septal defect CAVSD complete atrioventricular septal defect TOFtetralogy of Fallot DORV- PS double outlet right ventricle with pulmonary stenosis

CPB cardiopulmonary bypass Ao Cx aortic crossclamp P value is significant whenP lt 005 unpaired t test for age weight CBP Ao Cx and oropharyngeal temp

Fisherrsquos exact test for sex Chi-square test for pathology

Parameters of the study

Clinical outcome parameters

Intraoperative parametersThere was a significant difference

between both study groups after

declamping of the aorta Spon-taneous defibrillation into sinusrhythm occurred in 23 patients ofhot-shot group versus 10 patients of

control group (P value was 0002)Electrical defibrillation was requi-red in 7 patients of hotshot groupversus 20 patients of control group

(P value was 0002) (Table 4)

As regards requirement ofpacing to wean from cardio-pulmonary bypass there was no

significant difference between bothstudy groups Pacing was requiredin 5 patients of hot-shot groupversus 7 patients of control group (P

value was 0748) (Table 4)

As regards intraoperative

inotropes there was a significantdifference between both studygroups as regards number of

patients who required inotropes

for weaning of cardiopulmonarybypass Inotropes were requiredin 14 patients of hot-shot group

versus 24 patients of control group

(P value was 0015) (Table 4)

There was also a significantdifference between both groups as

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

19

regards inotropic score requiredfor weaning fromcardiopulmonary bypass Inotropescore was 44plusmn55 in hot-shot

group versus 105plusmn65 in controlgroup (P-value was lt0001)(Table 4)

Table 4 Intraoperative clinical outcome variablesControl

group

No =30

Hot-shot

group

No =30

P

value

Spontaneous defibrillation into sinusrhythm n ()

10 (333) 23 (767) 0002

Electrical defibrillation n () 20 (667) 7 (233) 0002

Requirement of pacing for weaning fromCBP n ()

7 (233) 5 (167) 0748

Requirement of intraoperative inotrope n

()24 (80) 14 (467) 0015

Inotrope score required for weaning from

CBP Mean plusmn SD 105plusmn

65 44plusmn

55 lt0001

n() Number (percentage) of patients Mean plusmnSD P-value is significant when Plt005 unpaired t

test for inotrope score P value is significant when P lt 005 Fisherrsquos exact test for spontaneous

defibrillation electrical defibrillation requirement of pacing and intraoperative inotrope

Postoperative parameters

There was a significant

difference between both studygroups as regards inotropes

required in the intensive careInotropes were required in 14

patients of hot-shot group versus24 patients of control group (Pvalue was 0015) Inotrope score

in the ICU was 754plusmn612 in hot-shot group versus 1225plusmn1032 incontrol group (P value was 0036)

Inotrope duration was 95plusmn72hrsin hot-shot group versus

149plusmn118hrs in control group (Pvalue was 0039) (Table 5)

As regards duration ofmechanical ventilation there was

no significant difference betweenboth study groups Duration ofmechanical ventilation was 67 plusmn 38

hrs in hot-shot group versus88plusmn44hrs in control group (Pvalue was 0053) (Table 5)

As regards duration of ICU

stay there was no significantdifference between both study

groups Duration of ICU stay was511plusmn188hrs in hot-shot groupversus 603plusmn231hrs in control

group (P-value was 0099) (Table

5)

There was no significantdifference between both study

groups as regards mortality Therewas no postoperative death in hot-shot group versus 3 postoperative

deaths in control group (P valuewas 0237) (Table 5)

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

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Comparison of cardioprotective effects Hussein Sabri et al

20

Table 5 Postoperative clinical outcome parametersControl

group

No =30

Hot-shot

group

No =30

P

value

Requirement of postoperative inotrope n () 24 (80) 14 (467) 0015

Inotrope score in ICU Meanplusmn SD 1225plusmn1032 754plusmn612 0036

Inotrope duration (h) Mean plusmn SD 149plusmn118 95plusmn72 0039

Duration of mechanical ventilation (h) Mean plusmn SD 88plusmn 44 67plusmn 38 0053

Duration of ICU stay (h) Mean plusmn SD 603 plusmn 231 511plusmn 188 0099

Mortality n () 3 (10) 0 (0) 0237

n () Number (percentage) of patients Mean plusmnSD P-value is significant when Plt005

unpaired t-test for inotrope score in ICU inotrope duration duration of mechanical Ventilation and duration of ICU stay P-value is significant when Plt005 Fisherrsquos exact test

for requirement of postoperative inotrope and mortality

Myocardial oxygen and lactate

extraction ratio As regards myo-

cardial oxygen extraction ratiothere was no significant differencebetween hot-shot group and

control group at the different

studied time intervals throughout

the initial sixty minutes ofreperfusion (P-value was gt005)(Table 6 Fig 1)

Table 6 Myocardial oxygen extraction ratio (MO2 ER)

Time interval after declamping of the aorta

Control

group

No =30

Hot-shot

group

No =30

P

value

M O2 ER immediately after declamping 529plusmn 62 512 plusmn 66 0308

M O2 ER 15 min after declamping 505plusmn 58 494 plusmn 61 0477

M O2 ER 30 min after declamping 492plusmn 55 480 plusmn 58 0414

M O2 ER 45 min after declamping 485plusmn 52 472 plusmn 55 0351

M O2 ER 60 min after declamping 476plusmn 51 468 plusmn 53 0554Mean plusmnSD P value is significant when P lt 005 unpaired t-test

983091983088

983091983093

983092983088

983092983093

983093983088

983093983093

983094983088

983088 983149983145983150 983089983093 983149983145983150 983091983088 983149983145983150 983092983093 983149983145983150 983094983088 983149983145983150

983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137

983117 983161 983151 983139 983137 983154 983140 983145 983137

983148 983151 983160 983161 983143 983141 983150 983141 983160 983156 983154 983137 983139 983156 983145 983151 983150 983154 983137 983156 983145 983151 983077 983139983151983150983156983154983151983148 983143983154983151983157983152

983144983151983156983085983155983144983151983156 983143983154983151983157983152

Fig 1 Myocardial oxygen extraction ratio Data are presented as mean Error bars represent

95 confidence interval

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

21

As regards myocardial lactateextraction ratio there was signi-ficant difference between hot-shotgroup and control group at the

different studied time intervals

throughout the initial sixtyminutes of reperfusion (P-valueswere 0027 0042 0024 lt0001lt0001 respectively) (Table 7

Fig 2)

Table 7 Myocardial lactate extraction ratio (M lactate ER)

Time interval after declamping of the aorta

Control

group

No =30

Hot-shot

group

No =30

P-

value

M lactate ER immediately after declamping -222plusmn 59 -190plusmn 50 0027

M lactate ER 15 min after declamping -136plusmn 50 -111plusmn 42 0042

M lactate ER 30 min after declamping -75plusmn 54 -44plusmn 49 0024

M lactate ER 45 min after declamping -48plusmn 40 00plusmn 46 lt0001

M lactate ER 60 min after declamping -26plusmn 34 59plusmn 41 lt0001

Mean plusmn SD P value is significant when Plt005 unpaired t-test

983085983091983088

983085983090983093

983085983090983088

983085983089983093

983085983089983088

983085983093

983088

983093

983089983088

983089983093

983090983088

983088 983149983145983150 983089983093 983149983145983150 983091983088 983149983145983150 983092983093 983149983145983150 983094983088 983149983145983150

983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137

983117 983161 983151 983139 983137 983154 983140 983145 983137 983148 983148 983137 983139 983156 983137 983156 983141 983141 983160 983156 983154 983137 983139 983156

983145 983151 983150 983154 983137 983156 983145 983151 983077

983139983151983150983156983154983151983148 983143983154983151983157983152

983144983151983156983085983155983144983151983156 983143983154983151983157983152

Fig 2 Myocardial lactate extraction ratio Data are presented as mean Error bars

represent 95 confidence interval P-value is significant when Plt005

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

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Comparison of cardioprotective effects Hussein Sabri et al

22

Serum level of cardiac troponinI (cTnI) There was no significantdifference between both studygroups as regards baseline values of

serum troponin I (P-value was0146) There was significantdifference between both study

groups in serum troponin I level at4 and 8 hours after declamping of

the aorta Serum troponin I level at

4 hours after declamping was132plusmn80ngml in hot-shot groupversus 313plusmn231ngml in controlgroup (P value was lt0001) Serum

troponin I level at 8 hours afterdeclamping was 100plusmn58ngml inhot-shot group versus 191plusmn115ngml in control group (P value waslt0001) (Table 8 Fig 3)

Table 8 Serum level of cardiac troponin I (cTnI)Control

group

No =30

Hot-shot

group

No =30

P

value

Baseline (ngml) 08plusmn

04 07plusmn

04 01464 hrs after declamping of the aorta (ngml) 313plusmn 231 132 plusmn 80 lt0001

8 hrs after declamping of the aorta (ngml) 191plusmn 115 100 plusmn 58 lt0001

Mean plusmn SD P-value is significant when P lt 005 unpaired t test

983088

983093

983089983088

983089983093

983090983088

983090983093

983091983088

983091983093

983092983088

983092983093

983138983137983155983141983148983145983150983141 983092 983144983154983155 983096 983144983154983155

983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137

983124 983154 983151 983152 983151 983150 983145 983150 983113 983080 983150 983143 983087 983149 983148 983081

983139983151983150983156983154983151983148 983143983154983151983157983152

983144983151983156983085983155983144983151983156 983143983154983151983157983152

Fig 3 Serum level of cardiac troponin I (cTnI) Data are presented as mean Errorbars represent 95 confidence interval P value is significant when P lt 005

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

23

Discussion

Low cardiac output aftersurgically induced ischemia andreperfusion continues to be a major

contributor to morbidity andmortality after pediatric cardiacsurgery and in more than 50 of

cases has been attributed toinadequate myocardial protection(Bull et al 1984 Hammon

1995)

Careful control of theconditions of reperfusion and the

composition of the reperfusate can

optimize postischemic recovery ofmyocardial function (Follette et

al 1981 Allen et al 1986)

The current study wasdesigned to evaluate the cardio-protective effect of using inter-mittent antegrade cold bloodcardioplegia versus intermittent

cold blood cardioplegia with ter-minal warm blood cardioplegia

(hot-shot) in pediatric cardiacpatients

The result of the current

study demonstrated significantdecrease in blood pressure at 5and 15 minutes interval in thecontrol group compared with the

hot-shot group after weaning ofthe cardiopulmonary bypass

Intermittent cold blood

cardioplegia with terminal warmblood cardioplegia offers favorable

effect on the clinical outcomeparameters This was demon-strated in this study as asignificant higher percentage ofspontaneous defibrillation into

sinus rhythm in hot-shot group

than control group (767 versus333 respectively)

The percentage of patientsrequiring inotropic support after

weaning from cardiopulmonarybypass was significantly higher incontrol group than hot-shot group

(80 versus 467 respectively)

By adopting the inotropic scoredescribed by Wernovsky et al

(1995) the level of inotropic

support was significantly lower inhot-shot group than control group

(44plusmn55 versus 105plusmn65 respec-

tively)

The improved clinical outcomerevealed the role of intermittent

cold blood cardioplegia withterminal warm blood cardioplegia inenhancement of myocardialprotection which was manifested asa reduction in myocardial arrhyth-

mia associated with ischemiareperfusion and a better myocardial

functionThe myocardial protective effect

of terminal warm blood cardioplegia

extended into the postoperativeperiod This was manifested as asignificant higher percentage ofpatients in control group than hot-

shot group who required inotropicsupport in the intensive care (80

versus 467 respectively) The

maximum dose of inotropic support(calculated by a modification of

inotropic score) was significantlyhigher in control group than hot-shot group (1225plusmn1032 versus754plusmn612 respectively) Theduration of inotropic support was

significantly higher in control group

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

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Comparison of cardioprotective effects Hussein Sabri et al

24

than hot-shot group (149plusmn118versus 95plusmn72 respectively)

In the postoperative periodresults were comparable as

regards duration of mechanicalventilation and stay in theintensive care unit in addition to

comparable mortality rate

Myocardial oxygen extraction

ratio reflects balance betweenmyocardial oxygen supply anddemand Myocardial oxygenextraction ratio was similar

between the two studied groups

This similarity may reflect theaerobic metabolic state of the

myocardium provided by the coldblood cardioplegia in both groups

Lactate release from theischemic myocytes is considered asa reflection of anaerobic metabolism(Krause et al 1993)

A negative myocardial lactateextraction ratio indicates that

amount of lactate productionthrough anaerobic glycolysis washigher than the amount of lactate

consumption for aerobic energy pro-duction with continuing anaerobicmetabolism and impairment ofnormal aerobic energy production

While a positive myocardial

lactate extraction ratio indicatesthat amount of lactate production

through anaerobic glycolysis wasless than the amount of lactate

consumption for aerobic energyproduction and that myocardiumstarts to use lactate as a substratevia oxidative phosphorylation

Myocardial lactate extractionratio in control group stayednegative value all through the sixtyminutes of studied period which

indicates impairment of aerobicmyocardial metabolism during thisperiod In hot-shot group myo-cardial lactate extraction ratioremained negative value till 45min

after declamping of the aorta when

it becomes a positive value

This point is considered a turnfrom anaerobic to aerobic meta-

bolism and it resembles the equilib-

rium between lactate consumptionand production At this point themyocardium starts to use lactate as

a substrate via oxidative phosphor-rylation (Krause et al 1993)

The results of this studydemonstrate the recovery of aerobicmetabolism afforded by inter-

mittent cold blood cardioplegia withterminal warm blood cardioplegiaTroponin I is a myocyte-contractileapparatus protein released follo-

wing myocardial damage Troponin

I Level is considered sensitivemarker of myocardial injuryassociated with cardiac surgery

(Immer et al 1998)

In this study we demonstrated

a significant increase in post-operative troponin I at 4 8 hoursafter declamping of the aorta in

control group compared to hot-shotgroup (P value was lt0001) Thisreflects the beneficial effect of warmcardioplegic reperfusion on myo-cardial outcome in reducing themyocardial damage following

ischemiareperfusion injury

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

25

In this study the composition ofterminal warm blood cardioplegiawas made to resemble the compo-sition of cold blood cardioplegia

used The point was to provide asolution with adequate potassiumconcentration to produce electro-mechanical arrest during reper-fusion This solution differs from the

conventional blood reperfusate in

presence of high potassiumconcentration (20mmolL-1) ahigher pH and a higher osmolarity

Thus cardioprotective effect ofterminal warm blood cardioplegia is

expected to be achieved byprolongation of electromechanicalarrest which reduces the energy

demands and counteracting tissueacidosis and edema therefore it

reduces the myocardial injury bypreservation and resynthesis ofhigh energy phosphates

There were small number ofclinical studies that have

examined specific myocardialprotection strategy in pediatric

population Utilizing an isolatedblood perfused neonatal heartpreparation Nomura et al

(2001) assessed the effects of

terminal warm blood cardioplegiaterminal warm oxygenated crys-talloid cardioplegia in comparisonwith conventional reperfusion(without any kind of terminal

cardioplegia) through assessmentrecovery of left ventricularfunction They demonstrated that

reperfusion with either terminalwarm blood cardioplegia or ter-

minal warm oxygenated crys-talloid cardioplegia resulted in

better recovery of myocardialfunction with slightly betterfunction in terminal warm bloodcardioplegia

In a clinically relevant intactanimal model that simulated theclinical condition of hypoxic

neonatal myocardium exposed toischemic stress Kronon et al

(2000) investigated the cardio-

protective effects of terminalwarm blood cardioplegic reper-fusion versus conventional reper-

fusion through assessment reco-

very of left ventricular systolicfunction and diastolic complianceThey showed that A warm cardio-

plegic reperfusion helps reduce

the reperfusion injury resultingin improved myocardial functionand metabolic recovery in hypoxicneonatal myocardium

Toyoda et al (2003) examined

the cardioprotective effect ofterminal warm blood cardioplegia inpediatric cardiac patients Blood

cardioplegia solution was composed

by mixing a hyperkalemic solutionwith oxygenated blood in 12dilutions with temperature 9oCThe terminal warm blood

cardioplegia had a finalconcentration of potassium 18mmolL-1 The results of Toyoda et alshowed beneficial effect of terminal

warm blood cardioplegia inreduction of myo-cardial injury Inagreement with Toyoda the

protocol of cardioplegiaadministered is almost similar asregard the concentration of pota-

ssium in terminal warm bloodcardioplegia (20mmolL-1) in 11

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Comparison of cardioprotective effects Hussein Sabri et al

26

dilution (1 crystalloid 1 blood) withsimilar result in myocardial pro-tection and improvement in aerobicenergy metabolism As a marker of

myocardial necrosis the currentstudy used troponin I whichprovides comparable information astroponin T used in the study ofToyoda

The current study is inagreement with Modi et al

(2004) who compared the use of

crystalloid cardioplegia cold blood

cardioplegia and cold blood

cardioplegia with hot-shot incyanotic and acyanotic pediatricpatients undergoing surgical

correction The efficacy of the 3

techniques was assessed byexamination right ventricularbiopsy specimen before and afterreperfusion analysis of cellular

metabolites and assessment oftroponin I level Their resultdemonstrated that for cyanotic

patients blood cardioplegia withhot-shot reduced metabolic injury

compared with cold crystalloidcardioplegia They also showed

that cold blood cardioplegia wason its own better than crystalloid

but not as good as cold bloodcardioplegia with hot-shot

Young et al (1997) failed to

demonstrate statistical advantage

for blood cardioplegia over crys-talloid cardioplegia in surgery forcongenital heart The most impor-

tant aspect of the study of Younget al is that no obvious benefitcan be anticipated by use of blood

cardioplegia in congenital heartsurgery when only antegrade

hypothermia dosing technique isused The integrated cardioplegicapproach using warm cold ante-grade and retrograde technique

with substrate enrichment may bebeneficial for pediatric population

As conclusion the result of

the current study showed that theuse of cardioplegia with hot-shot

provides the criteria that mayimprove myocardial protectionand reduce myocardial injury inpediatric population

These criteria include warm

blood accelerates recovery oftemperature-dependent enzymatic

and metabolic function highpotassium concentration prolongs

electromechanical arrest to decreaseenergy demands alkaloid solutionwhich counteracts tissue acidosisand high osmolarity which coun-teracts tissue edema

References

1 Allen BS Okamoto F

Buckberg GD Bugyi H

Young H Leaf J

Beyersdorf F Sjostrand F

and Maloney JV Jr

Studies of controlledreperfusion after ischemiaXV Immediate functional

recovery after six hours of

regional ischemia by careful

control of conditions ofreperfusion and compositionof reperfusate J Thorac

Cardiovasc Surg 1986 92(3Pt 2) 621-35

2 Allen BS Current Conceptsin Pediatric Myocardial

Protection In Salerno TA and

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

27

Ricci M (editors) MyocardialProtection 1st editionBlackwell publishing 2004207-29

3 Allen BS Pediatricmyocardial protection acardioplegic stra-tegy is the

solution Semin Thorac

Cardiovasc Surg Pediatr CardSurg Annu 2004 7 141-54

4 Bull C Cooper J and

Stark J Cardioplegicprotection of the childrsquos

heart J Thorac Cardio-vasc

Surg 1984 88(2) 287-93

5 Caputo M Dihmis WC

Bryan AJ Suleiman MS

and Angelini GD Warmblood hyperkalaemicreperfusion (hot shot)prevents myocardial substratederangement in patients

undergoing coronary arterybypass surgery Eur J

Cardiothorac Surg 199813(5) 559-64

6 Follette DM Fey K

Buckberg GD Helly JJ Jr

Steed DL Foglia RP and

Maloney JV Jr Reducingpostischemic damage by

temporary modifi-cation ofreperfusate calcium

potassium pH and

osmolarity J ThoracCardiovasc Surg 1981 82 (2)

221-38

7 Hammon JW Jr Myocardialprotection in the immatureheart Ann Thorac Surg 1995

60 (3) 839-842

8 Immer FF Stocker FP

Seiler AM Pfammatter JP

Printzen G and Carrel TP

Comparison of troponin-I and

troponin-T after pediatriccardiovascular opera-tion

Ann Thorac Surg 1998 66 (6)2073-7

9 Krause EG Pfeiffer D

Wollen-berger U and

Wollert HG Lactatemonitoring during and aftercardiopulmonary bypass an

approach implicating a peri-

operative measure for cardiacenergy metabolism In PiperHM Preusse CJ (editors)

Ischemia-reperfusion in

cardiac surgery 1st editionKluwer Academic 1993 317-33

10 Kronon MT Allen BS

Rahman S Wang T

Tayyab NA Bolling KS and

Ilbawi MN Reducingpostischemic reper-fusion

damage in neonates using a

terminal warm substrate-enriched blood cardioplegicreperfusate Ann Thorac Surg2000 70(3) 765-770

11 Modi P Suleiman MS

Reeves B Pawade A Parry

AJ Angelini GD and

Caputo M Myocardial

metabolic changes during ped-iatric cardiac surgery arando-mized study of 3cardioplegic techniques JThorac Cardiovasc Surg2004 128(1) 67-75

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

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Comparison of cardioprotective effects Hussein Sabri et al

28

12 Nomura F Forbess JM

and Mayer EJ Effects ofHot shot on recovery afterhypothermic ischemia in

neonatal lamb heart JCardiovasc Surg (Torino)2001 42(1) 1-7

13 Teoh KH Christakis GT

Weisel RD Fremes SE

Mickle DA Romaschin AD

Harding RS Ivanov J

Madonik MM Ross IM et

al Accelerated myocardial

metabolic recovery with

terminal warm bloodcardioplegia J ThoracCardiovasc Surg 1986 91(6)

888-95

14 Toyoda Y Yamaguchi M

Yoshimura N Oka S and

Okita Y Cardioprotectiveeffects and the mechanisms of

terminal warm bloodcardioplegia in pediatriccardiac surgery J ThoracCardiovasc Surg 2003 125

(6) 1242-51

15 Wernovsky G Wypij D

Jonas RA Mayer JE Jr

Hanley FL Hickey PR

Walsh AZ Chang AC

Castaneda AR NewburgerJW et al Postoperativecourse and hemodynamicprofile after the arterial

switch operation in neo-natesand infants A comparison of

low-flow cardiopulmonarybypass and circulatory arrestCirculation 1995 92(8) 2226-

35

16 Young JN Choy IO SilvaNK Obayashi DY and

Barkan HE Antegrade cold

blood cardioplegia is not

demonstrably advan-tageousover cold crystalloidcardioplegia in surgery forcongenital heart disease J

Thorac Cardiovasc Surg1997 114(6) 1002-9

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

13

blood reperfusion just beforedeclamping of the aorta

The study population wasstratified based on clinical

diagnosis patients with right toleft shunt visualized by echo-cardiography were considered

cyanotic others considered non-cyanotic

Inclusion criteria Patients ofboth sexes presented for electiverepair of congenital heart diseaseBody weight 10-25kg Age12month-36month Exclusion

criteria Patients underwentpalliative operation (eg shuntpulmonary artery banding) andpresented for total repair Patientsunderwent previous repair andpresented for redo operationPatients on preoperative inotropicsupport Patients on preoperativemechanical ventilation

Anesthetic management Anesthetic technique was stan-

dardized for all patients Childrenshould have no milk formula orsolids for 6hrs prior to surgeryClear liquids are allowed up to 3hours preoperatively

Preoperative assessment After careful history taking a tho-rough physical examination wasdone This included assessment ofthe general condition chest exami-nation and measurement of axi-llary temperature Laboratorystudies chest x-ray and results ofechocardiography and catheteri-zation studies were reviewed

Premedication Patients were

premedicated with oral midazolamat a dose of 05mgkg-1 given 15min

before induction of anesthesia tofacilitate quiet separation from theparents

Induction of anesthesia

Anesthesia was induced withinhalation of halothane 2-3 in100 oxygen by face mask till a

peripheral venous cannula was

inserted and secured Then ane-sthesia was completed throughfentanyl 2microgkg-1 IV Trachealintubation was facilitated withpancuronium 01mgkg-1 IV

Ventilation was mechanically

controlled by Ohmeda 7800 venti-lator to deliver tidal volume of

10mlkg-1 respiratory rate wasadjusted achieve a partial pre-

ssure of carbon dioxide [PaCO2] of32-36mmHg

Monitoring On arrival to

operative theater patients were

monitored by electrocardiogram(lead II) pulse oximetry and non

invasive blood pressure Immed-iately after anesthetic inductionleft radial arterial catheter was

inserted after modified Allenstest for invasive blood pressuremonitoring and arterial bloodsampling Right internal jugular

triple lumen venous catheter wasalso inserted for monitoring ofcentral venous pressure andinfusing inotropes crystalloids

blood plasma and other drugs

Oropharyngeal temperaturewas also monitored All previousparameters were monitored usinga modular monitor (Hewlett-Packard model 64s) Arterial

blood samples were taken for

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Comparison of cardioprotective effects Hussein Sabri et al

14

blood gas acid base andelectrolytes analysis to correctany change in the ventilationelectrolytes or acid base balance

of the patient Maintenance of anesthesia

Anesthesia was maintained by

isoflurane 02-04 in 50 oxygen

air mixture extra analgesia wasprovided by fentanyl 10microgkg-1 IVbefore sternotomy in incrementsPancuronium in a dose of002mgkg-1 IV was used as

increment for adequate muscle

relaxation Management of cardio-

pulmonary bypass Immediately

after anesthetic induction activatedclotting time (ACT) was measuredand used as a control Anti-coagulation was achieved byadministration of heparin sulphate

3mgkg-1 IV and adjusted tomaintain ACT more than 480seconds Priming of Cardiopul-monary bypass (CPB) circuit

consisted of ringer solution

manifold sodium bicarbonate andblood or plasma depending oninitial hematocrit CPB wasestablished between ascending

aortic and bicaval cannulation CPBwas instituted using non-pulsatileflow ranging between 100-150mlkg-1min-1 to maintain mean

arterial pressure between 40-60mmHg

At full flow of CBP mecha-nical ventilation was stopped and

the lungs remained collapsed atthe functional residual capacityModerate systemic hypothermiawas used [28degC-32degC] Alpha stat

strategy for pH management wasadopted Hematocrit was main-tained above 25

Protocol of myocardial pro-tection In control group (C) Myo-

cardial protection was achievedwith intermittent antegrade coldblood cardioplegia with topicalheart cooling in all patients

Cardioplegic solution of 20mLKg-1

of body weight was initially infusedinto the aortic root after applicationof aortic cross clamp to achieve

cardiac arrest with subsequent

doses every 20min Blood cardio-plegia was prepared by mixingoxygenated blood with hyper-kalemic crystalloid solution in 11ratio with sodium bicarbonate

added as buffer lidocaine as mem-brane stabilizer and cooled to 9degC

[Table 1] [Table 2]

In hot-shot group (HS) Cardio-

plegic regimen was the same withan additional 20mLKg-1 of body

weight of warm (35degC) bloodcardioplegia was infused into the

aortic root just before declamping ofthe aorta The composition ofterminal warm blood cardioplegiawas the same as the cold blood

cardioplegia other than tempera-ture

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

15

Table (1) Components added to crystalloid solution per liter

KCl 40 mmol L-1

NaHCO3 40 mmol L-1

Lidocaine 100 mg L-1

Table (2) Final composition of cardioplegia after mixing oxygenatedblood with hyperkalemic crystalloid solution in 11 ratio

pH 76

Hematocrit 17-22

K + 20 mmol L-1

Na+ 150 mmol L-1

Cl+ 150 mmol L-1

Ca2+ 2 mmol L-1

Osmolaritv 380 mOsm L-1

Weaning of cardiopul-

monary bypass After completion

of the surgical repair rewarming

was instituted Standard deairingmaneuvers were performed beforeremoval of the aortic cross-clamp

Ventricular distention during re-perfusion was avoided by regu-

lation of systemic venous return

and ventricular vent Electricaldefibrillation was applied to theheart if ventricular fibrillation

persisted Pacing the heart was

applied if there was second orthird degree heart block orintractable sinus bradycardia

Once optimal heart rate

electrolyte acid-base and tem-perature were achieved mechanicalventilation was resumed Afteroptimizing preload and afterload

CBP was gradually stopped If

systolic blood pressure was lowerthan 80 mm Hg despite centralvenous pressure above 10cm H2Odobutamine was our first choice

inotrope [dobutamine infusion

starting at a dose of 5-15microgkg-1 min-1] Epinephrine was our secondchoice when dobutamine alone was

ineffective [epinephrine infusionstarting at a dose of 50-250ngkg-1

min-1] Inotrope dose was titratedaccording to the hemodynamic andclinical state of the patient

At the end of bypass

protamine sulfate in a dose of15mg per 1mg heparin was usedto neutralize heparin effect The

chest was then closed in routine

fashion once meticulous hemos-tasis was achieved

Postoperative care Patient

admitted to pediatric cardiac sur-

gery intensive care unit Routinepostoperative management wasgiven to all patients Decision regar-ding ventilation and inotrope were

based on unit protocol hemody-

namic status and clinical judgment

Parameters of the study

Assessment of clinical outcomeIntraoperative and postoperative

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

17

O2 content CS oxygen content incoronary sinus blood sample

Myocardial lactate extraction

ratio was calculated according to

the following equation

Myocardial lactate extractionrate ratio= [lactate A - lactate CS] x100lactate A

Lactate A serum lactate concen-tration in arterial blood sample

Lactate CS serum lactate concen-

tration in coronary sinus bloodsample

Serum level of cardiac

troponin I (cTnI) Two millilitersof blood sample collected fromeach patient after induction of

anesthesia and at 4 8hrs afterdeclamping of the aorta Bloodsamples were centrifuged and

stored at -20deg until the completionof the study when thawed once

and assays were performed by a

laboratory technician blinded tothe clinical status of the patientor their inclusion in the studySerum concentration of cardiac

troponin I was determined with acommercially available enzyme-linked immunosorbent assay

(ELISA) kits cTnI ELISA-DRG

international Inc

Principle of the test Sample

was allowed to react with themicrotiter coated with monoclonalanti troponin I antibody (solid

phase) Monoclonal anti troponinI-enzyme (horseradish peroxidase)conjugate solution was added

resulting in the troponin I molec-

ules being sandwiched between

the solid phase and enzyme-linked antibodies

A solution of tetramethyl-benzidine (TMB) reagent was added

and incubated for 20 minutesresulting in the development of ablue color The color development

was stopped with the addition of 1Nhydrochloric acid (HCl) changing

the color to yellow The concen-tration of troponin I was directlyproportional to the color intensity ofthe test sample Absorbance was

measured spectrophotometrically

using Dade Behring Inc BEPreg

IIIat wavelength 450nm

Statistical analysis

All data were prospectively

collected coded tabulated thensubjected to statistical analysisusing SPSSreg for Windows version150 software packages Numericalvariables were presented as mean

and standard deviation (SD) while

categorical variables were presen-ted as number of cases and percent

Between-groups comparisons of

numerical variables were performedwith unpaired student-t test whilethose of categorical variables wereperformed by Fisher exact test orChi-square test as appropriate For

all tests P-value of less than 005

was considered statistically signifi-

cantResults

Patientsrsquo characteristics and

intraoperative data The demog-

raphic data and patients pathology

were comparable in both studygroups as shown in (Table 3)

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Comparison of cardioprotective effects Hussein Sabri et al

18

Intraoperative variables were alsocomparable in both study groups asshown in (Table 3) There was nosignificant difference as regards

cardiopulmonary bypass time (P

value was 0621) aortic cross-clamptime (P value was 0916) lowestoropharyngeal temperature (Pvalue was 0749)

Table 3 Patientsrsquo characteristics and intraoperative dataControl group

No =30

Hot-shot group

No =30P value

Age (month) 175 plusmn 56 181 plusmn 57 0716

Sex (MF) 1416 1614 0797

Weight (Kg) 141 plusmn 38 148 plusmn 42 0481

Pathology (n)

Acyanotic 17 19 ASD 6 7

VSD 7 9

CAVSD 4 3

Cyanotic 13 11

TOF 7 6

DORV- PS 6 5

CBP (min) 643plusmn 259 679plusmn 288 0621

Ao Cx (min) 378plusmn 169 382plusmn 171 0916

Oropharyngeal temp (degC) 306 plusmn 22 307 plusmn 20 0749

Mean plusmn SD MF male female ratio n number of patients ASD atrial septal defect

VSD ventricular septal defect CAVSD complete atrioventricular septal defect TOFtetralogy of Fallot DORV- PS double outlet right ventricle with pulmonary stenosis

CPB cardiopulmonary bypass Ao Cx aortic crossclamp P value is significant whenP lt 005 unpaired t test for age weight CBP Ao Cx and oropharyngeal temp

Fisherrsquos exact test for sex Chi-square test for pathology

Parameters of the study

Clinical outcome parameters

Intraoperative parametersThere was a significant difference

between both study groups after

declamping of the aorta Spon-taneous defibrillation into sinusrhythm occurred in 23 patients ofhot-shot group versus 10 patients of

control group (P value was 0002)Electrical defibrillation was requi-red in 7 patients of hotshot groupversus 20 patients of control group

(P value was 0002) (Table 4)

As regards requirement ofpacing to wean from cardio-pulmonary bypass there was no

significant difference between bothstudy groups Pacing was requiredin 5 patients of hot-shot groupversus 7 patients of control group (P

value was 0748) (Table 4)

As regards intraoperative

inotropes there was a significantdifference between both studygroups as regards number of

patients who required inotropes

for weaning of cardiopulmonarybypass Inotropes were requiredin 14 patients of hot-shot group

versus 24 patients of control group

(P value was 0015) (Table 4)

There was also a significantdifference between both groups as

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

19

regards inotropic score requiredfor weaning fromcardiopulmonary bypass Inotropescore was 44plusmn55 in hot-shot

group versus 105plusmn65 in controlgroup (P-value was lt0001)(Table 4)

Table 4 Intraoperative clinical outcome variablesControl

group

No =30

Hot-shot

group

No =30

P

value

Spontaneous defibrillation into sinusrhythm n ()

10 (333) 23 (767) 0002

Electrical defibrillation n () 20 (667) 7 (233) 0002

Requirement of pacing for weaning fromCBP n ()

7 (233) 5 (167) 0748

Requirement of intraoperative inotrope n

()24 (80) 14 (467) 0015

Inotrope score required for weaning from

CBP Mean plusmn SD 105plusmn

65 44plusmn

55 lt0001

n() Number (percentage) of patients Mean plusmnSD P-value is significant when Plt005 unpaired t

test for inotrope score P value is significant when P lt 005 Fisherrsquos exact test for spontaneous

defibrillation electrical defibrillation requirement of pacing and intraoperative inotrope

Postoperative parameters

There was a significant

difference between both studygroups as regards inotropes

required in the intensive careInotropes were required in 14

patients of hot-shot group versus24 patients of control group (Pvalue was 0015) Inotrope score

in the ICU was 754plusmn612 in hot-shot group versus 1225plusmn1032 incontrol group (P value was 0036)

Inotrope duration was 95plusmn72hrsin hot-shot group versus

149plusmn118hrs in control group (Pvalue was 0039) (Table 5)

As regards duration ofmechanical ventilation there was

no significant difference betweenboth study groups Duration ofmechanical ventilation was 67 plusmn 38

hrs in hot-shot group versus88plusmn44hrs in control group (Pvalue was 0053) (Table 5)

As regards duration of ICU

stay there was no significantdifference between both study

groups Duration of ICU stay was511plusmn188hrs in hot-shot groupversus 603plusmn231hrs in control

group (P-value was 0099) (Table

5)

There was no significantdifference between both study

groups as regards mortality Therewas no postoperative death in hot-shot group versus 3 postoperative

deaths in control group (P valuewas 0237) (Table 5)

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

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Comparison of cardioprotective effects Hussein Sabri et al

20

Table 5 Postoperative clinical outcome parametersControl

group

No =30

Hot-shot

group

No =30

P

value

Requirement of postoperative inotrope n () 24 (80) 14 (467) 0015

Inotrope score in ICU Meanplusmn SD 1225plusmn1032 754plusmn612 0036

Inotrope duration (h) Mean plusmn SD 149plusmn118 95plusmn72 0039

Duration of mechanical ventilation (h) Mean plusmn SD 88plusmn 44 67plusmn 38 0053

Duration of ICU stay (h) Mean plusmn SD 603 plusmn 231 511plusmn 188 0099

Mortality n () 3 (10) 0 (0) 0237

n () Number (percentage) of patients Mean plusmnSD P-value is significant when Plt005

unpaired t-test for inotrope score in ICU inotrope duration duration of mechanical Ventilation and duration of ICU stay P-value is significant when Plt005 Fisherrsquos exact test

for requirement of postoperative inotrope and mortality

Myocardial oxygen and lactate

extraction ratio As regards myo-

cardial oxygen extraction ratiothere was no significant differencebetween hot-shot group and

control group at the different

studied time intervals throughout

the initial sixty minutes ofreperfusion (P-value was gt005)(Table 6 Fig 1)

Table 6 Myocardial oxygen extraction ratio (MO2 ER)

Time interval after declamping of the aorta

Control

group

No =30

Hot-shot

group

No =30

P

value

M O2 ER immediately after declamping 529plusmn 62 512 plusmn 66 0308

M O2 ER 15 min after declamping 505plusmn 58 494 plusmn 61 0477

M O2 ER 30 min after declamping 492plusmn 55 480 plusmn 58 0414

M O2 ER 45 min after declamping 485plusmn 52 472 plusmn 55 0351

M O2 ER 60 min after declamping 476plusmn 51 468 plusmn 53 0554Mean plusmnSD P value is significant when P lt 005 unpaired t-test

983091983088

983091983093

983092983088

983092983093

983093983088

983093983093

983094983088

983088 983149983145983150 983089983093 983149983145983150 983091983088 983149983145983150 983092983093 983149983145983150 983094983088 983149983145983150

983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137

983117 983161 983151 983139 983137 983154 983140 983145 983137

983148 983151 983160 983161 983143 983141 983150 983141 983160 983156 983154 983137 983139 983156 983145 983151 983150 983154 983137 983156 983145 983151 983077 983139983151983150983156983154983151983148 983143983154983151983157983152

983144983151983156983085983155983144983151983156 983143983154983151983157983152

Fig 1 Myocardial oxygen extraction ratio Data are presented as mean Error bars represent

95 confidence interval

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

21

As regards myocardial lactateextraction ratio there was signi-ficant difference between hot-shotgroup and control group at the

different studied time intervals

throughout the initial sixtyminutes of reperfusion (P-valueswere 0027 0042 0024 lt0001lt0001 respectively) (Table 7

Fig 2)

Table 7 Myocardial lactate extraction ratio (M lactate ER)

Time interval after declamping of the aorta

Control

group

No =30

Hot-shot

group

No =30

P-

value

M lactate ER immediately after declamping -222plusmn 59 -190plusmn 50 0027

M lactate ER 15 min after declamping -136plusmn 50 -111plusmn 42 0042

M lactate ER 30 min after declamping -75plusmn 54 -44plusmn 49 0024

M lactate ER 45 min after declamping -48plusmn 40 00plusmn 46 lt0001

M lactate ER 60 min after declamping -26plusmn 34 59plusmn 41 lt0001

Mean plusmn SD P value is significant when Plt005 unpaired t-test

983085983091983088

983085983090983093

983085983090983088

983085983089983093

983085983089983088

983085983093

983088

983093

983089983088

983089983093

983090983088

983088 983149983145983150 983089983093 983149983145983150 983091983088 983149983145983150 983092983093 983149983145983150 983094983088 983149983145983150

983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137

983117 983161 983151 983139 983137 983154 983140 983145 983137 983148 983148 983137 983139 983156 983137 983156 983141 983141 983160 983156 983154 983137 983139 983156

983145 983151 983150 983154 983137 983156 983145 983151 983077

983139983151983150983156983154983151983148 983143983154983151983157983152

983144983151983156983085983155983144983151983156 983143983154983151983157983152

Fig 2 Myocardial lactate extraction ratio Data are presented as mean Error bars

represent 95 confidence interval P-value is significant when Plt005

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

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Comparison of cardioprotective effects Hussein Sabri et al

22

Serum level of cardiac troponinI (cTnI) There was no significantdifference between both studygroups as regards baseline values of

serum troponin I (P-value was0146) There was significantdifference between both study

groups in serum troponin I level at4 and 8 hours after declamping of

the aorta Serum troponin I level at

4 hours after declamping was132plusmn80ngml in hot-shot groupversus 313plusmn231ngml in controlgroup (P value was lt0001) Serum

troponin I level at 8 hours afterdeclamping was 100plusmn58ngml inhot-shot group versus 191plusmn115ngml in control group (P value waslt0001) (Table 8 Fig 3)

Table 8 Serum level of cardiac troponin I (cTnI)Control

group

No =30

Hot-shot

group

No =30

P

value

Baseline (ngml) 08plusmn

04 07plusmn

04 01464 hrs after declamping of the aorta (ngml) 313plusmn 231 132 plusmn 80 lt0001

8 hrs after declamping of the aorta (ngml) 191plusmn 115 100 plusmn 58 lt0001

Mean plusmn SD P-value is significant when P lt 005 unpaired t test

983088

983093

983089983088

983089983093

983090983088

983090983093

983091983088

983091983093

983092983088

983092983093

983138983137983155983141983148983145983150983141 983092 983144983154983155 983096 983144983154983155

983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137

983124 983154 983151 983152 983151 983150 983145 983150 983113 983080 983150 983143 983087 983149 983148 983081

983139983151983150983156983154983151983148 983143983154983151983157983152

983144983151983156983085983155983144983151983156 983143983154983151983157983152

Fig 3 Serum level of cardiac troponin I (cTnI) Data are presented as mean Errorbars represent 95 confidence interval P value is significant when P lt 005

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

23

Discussion

Low cardiac output aftersurgically induced ischemia andreperfusion continues to be a major

contributor to morbidity andmortality after pediatric cardiacsurgery and in more than 50 of

cases has been attributed toinadequate myocardial protection(Bull et al 1984 Hammon

1995)

Careful control of theconditions of reperfusion and the

composition of the reperfusate can

optimize postischemic recovery ofmyocardial function (Follette et

al 1981 Allen et al 1986)

The current study wasdesigned to evaluate the cardio-protective effect of using inter-mittent antegrade cold bloodcardioplegia versus intermittent

cold blood cardioplegia with ter-minal warm blood cardioplegia

(hot-shot) in pediatric cardiacpatients

The result of the current

study demonstrated significantdecrease in blood pressure at 5and 15 minutes interval in thecontrol group compared with the

hot-shot group after weaning ofthe cardiopulmonary bypass

Intermittent cold blood

cardioplegia with terminal warmblood cardioplegia offers favorable

effect on the clinical outcomeparameters This was demon-strated in this study as asignificant higher percentage ofspontaneous defibrillation into

sinus rhythm in hot-shot group

than control group (767 versus333 respectively)

The percentage of patientsrequiring inotropic support after

weaning from cardiopulmonarybypass was significantly higher incontrol group than hot-shot group

(80 versus 467 respectively)

By adopting the inotropic scoredescribed by Wernovsky et al

(1995) the level of inotropic

support was significantly lower inhot-shot group than control group

(44plusmn55 versus 105plusmn65 respec-

tively)

The improved clinical outcomerevealed the role of intermittent

cold blood cardioplegia withterminal warm blood cardioplegia inenhancement of myocardialprotection which was manifested asa reduction in myocardial arrhyth-

mia associated with ischemiareperfusion and a better myocardial

functionThe myocardial protective effect

of terminal warm blood cardioplegia

extended into the postoperativeperiod This was manifested as asignificant higher percentage ofpatients in control group than hot-

shot group who required inotropicsupport in the intensive care (80

versus 467 respectively) The

maximum dose of inotropic support(calculated by a modification of

inotropic score) was significantlyhigher in control group than hot-shot group (1225plusmn1032 versus754plusmn612 respectively) Theduration of inotropic support was

significantly higher in control group

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Comparison of cardioprotective effects Hussein Sabri et al

24

than hot-shot group (149plusmn118versus 95plusmn72 respectively)

In the postoperative periodresults were comparable as

regards duration of mechanicalventilation and stay in theintensive care unit in addition to

comparable mortality rate

Myocardial oxygen extraction

ratio reflects balance betweenmyocardial oxygen supply anddemand Myocardial oxygenextraction ratio was similar

between the two studied groups

This similarity may reflect theaerobic metabolic state of the

myocardium provided by the coldblood cardioplegia in both groups

Lactate release from theischemic myocytes is considered asa reflection of anaerobic metabolism(Krause et al 1993)

A negative myocardial lactateextraction ratio indicates that

amount of lactate productionthrough anaerobic glycolysis washigher than the amount of lactate

consumption for aerobic energy pro-duction with continuing anaerobicmetabolism and impairment ofnormal aerobic energy production

While a positive myocardial

lactate extraction ratio indicatesthat amount of lactate production

through anaerobic glycolysis wasless than the amount of lactate

consumption for aerobic energyproduction and that myocardiumstarts to use lactate as a substratevia oxidative phosphorylation

Myocardial lactate extractionratio in control group stayednegative value all through the sixtyminutes of studied period which

indicates impairment of aerobicmyocardial metabolism during thisperiod In hot-shot group myo-cardial lactate extraction ratioremained negative value till 45min

after declamping of the aorta when

it becomes a positive value

This point is considered a turnfrom anaerobic to aerobic meta-

bolism and it resembles the equilib-

rium between lactate consumptionand production At this point themyocardium starts to use lactate as

a substrate via oxidative phosphor-rylation (Krause et al 1993)

The results of this studydemonstrate the recovery of aerobicmetabolism afforded by inter-

mittent cold blood cardioplegia withterminal warm blood cardioplegiaTroponin I is a myocyte-contractileapparatus protein released follo-

wing myocardial damage Troponin

I Level is considered sensitivemarker of myocardial injuryassociated with cardiac surgery

(Immer et al 1998)

In this study we demonstrated

a significant increase in post-operative troponin I at 4 8 hoursafter declamping of the aorta in

control group compared to hot-shotgroup (P value was lt0001) Thisreflects the beneficial effect of warmcardioplegic reperfusion on myo-cardial outcome in reducing themyocardial damage following

ischemiareperfusion injury

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

25

In this study the composition ofterminal warm blood cardioplegiawas made to resemble the compo-sition of cold blood cardioplegia

used The point was to provide asolution with adequate potassiumconcentration to produce electro-mechanical arrest during reper-fusion This solution differs from the

conventional blood reperfusate in

presence of high potassiumconcentration (20mmolL-1) ahigher pH and a higher osmolarity

Thus cardioprotective effect ofterminal warm blood cardioplegia is

expected to be achieved byprolongation of electromechanicalarrest which reduces the energy

demands and counteracting tissueacidosis and edema therefore it

reduces the myocardial injury bypreservation and resynthesis ofhigh energy phosphates

There were small number ofclinical studies that have

examined specific myocardialprotection strategy in pediatric

population Utilizing an isolatedblood perfused neonatal heartpreparation Nomura et al

(2001) assessed the effects of

terminal warm blood cardioplegiaterminal warm oxygenated crys-talloid cardioplegia in comparisonwith conventional reperfusion(without any kind of terminal

cardioplegia) through assessmentrecovery of left ventricularfunction They demonstrated that

reperfusion with either terminalwarm blood cardioplegia or ter-

minal warm oxygenated crys-talloid cardioplegia resulted in

better recovery of myocardialfunction with slightly betterfunction in terminal warm bloodcardioplegia

In a clinically relevant intactanimal model that simulated theclinical condition of hypoxic

neonatal myocardium exposed toischemic stress Kronon et al

(2000) investigated the cardio-

protective effects of terminalwarm blood cardioplegic reper-fusion versus conventional reper-

fusion through assessment reco-

very of left ventricular systolicfunction and diastolic complianceThey showed that A warm cardio-

plegic reperfusion helps reduce

the reperfusion injury resultingin improved myocardial functionand metabolic recovery in hypoxicneonatal myocardium

Toyoda et al (2003) examined

the cardioprotective effect ofterminal warm blood cardioplegia inpediatric cardiac patients Blood

cardioplegia solution was composed

by mixing a hyperkalemic solutionwith oxygenated blood in 12dilutions with temperature 9oCThe terminal warm blood

cardioplegia had a finalconcentration of potassium 18mmolL-1 The results of Toyoda et alshowed beneficial effect of terminal

warm blood cardioplegia inreduction of myo-cardial injury Inagreement with Toyoda the

protocol of cardioplegiaadministered is almost similar asregard the concentration of pota-

ssium in terminal warm bloodcardioplegia (20mmolL-1) in 11

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Comparison of cardioprotective effects Hussein Sabri et al

26

dilution (1 crystalloid 1 blood) withsimilar result in myocardial pro-tection and improvement in aerobicenergy metabolism As a marker of

myocardial necrosis the currentstudy used troponin I whichprovides comparable information astroponin T used in the study ofToyoda

The current study is inagreement with Modi et al

(2004) who compared the use of

crystalloid cardioplegia cold blood

cardioplegia and cold blood

cardioplegia with hot-shot incyanotic and acyanotic pediatricpatients undergoing surgical

correction The efficacy of the 3

techniques was assessed byexamination right ventricularbiopsy specimen before and afterreperfusion analysis of cellular

metabolites and assessment oftroponin I level Their resultdemonstrated that for cyanotic

patients blood cardioplegia withhot-shot reduced metabolic injury

compared with cold crystalloidcardioplegia They also showed

that cold blood cardioplegia wason its own better than crystalloid

but not as good as cold bloodcardioplegia with hot-shot

Young et al (1997) failed to

demonstrate statistical advantage

for blood cardioplegia over crys-talloid cardioplegia in surgery forcongenital heart The most impor-

tant aspect of the study of Younget al is that no obvious benefitcan be anticipated by use of blood

cardioplegia in congenital heartsurgery when only antegrade

hypothermia dosing technique isused The integrated cardioplegicapproach using warm cold ante-grade and retrograde technique

with substrate enrichment may bebeneficial for pediatric population

As conclusion the result of

the current study showed that theuse of cardioplegia with hot-shot

provides the criteria that mayimprove myocardial protectionand reduce myocardial injury inpediatric population

These criteria include warm

blood accelerates recovery oftemperature-dependent enzymatic

and metabolic function highpotassium concentration prolongs

electromechanical arrest to decreaseenergy demands alkaloid solutionwhich counteracts tissue acidosisand high osmolarity which coun-teracts tissue edema

References

1 Allen BS Okamoto F

Buckberg GD Bugyi H

Young H Leaf J

Beyersdorf F Sjostrand F

and Maloney JV Jr

Studies of controlledreperfusion after ischemiaXV Immediate functional

recovery after six hours of

regional ischemia by careful

control of conditions ofreperfusion and compositionof reperfusate J Thorac

Cardiovasc Surg 1986 92(3Pt 2) 621-35

2 Allen BS Current Conceptsin Pediatric Myocardial

Protection In Salerno TA and

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

27

Ricci M (editors) MyocardialProtection 1st editionBlackwell publishing 2004207-29

3 Allen BS Pediatricmyocardial protection acardioplegic stra-tegy is the

solution Semin Thorac

Cardiovasc Surg Pediatr CardSurg Annu 2004 7 141-54

4 Bull C Cooper J and

Stark J Cardioplegicprotection of the childrsquos

heart J Thorac Cardio-vasc

Surg 1984 88(2) 287-93

5 Caputo M Dihmis WC

Bryan AJ Suleiman MS

and Angelini GD Warmblood hyperkalaemicreperfusion (hot shot)prevents myocardial substratederangement in patients

undergoing coronary arterybypass surgery Eur J

Cardiothorac Surg 199813(5) 559-64

6 Follette DM Fey K

Buckberg GD Helly JJ Jr

Steed DL Foglia RP and

Maloney JV Jr Reducingpostischemic damage by

temporary modifi-cation ofreperfusate calcium

potassium pH and

osmolarity J ThoracCardiovasc Surg 1981 82 (2)

221-38

7 Hammon JW Jr Myocardialprotection in the immatureheart Ann Thorac Surg 1995

60 (3) 839-842

8 Immer FF Stocker FP

Seiler AM Pfammatter JP

Printzen G and Carrel TP

Comparison of troponin-I and

troponin-T after pediatriccardiovascular opera-tion

Ann Thorac Surg 1998 66 (6)2073-7

9 Krause EG Pfeiffer D

Wollen-berger U and

Wollert HG Lactatemonitoring during and aftercardiopulmonary bypass an

approach implicating a peri-

operative measure for cardiacenergy metabolism In PiperHM Preusse CJ (editors)

Ischemia-reperfusion in

cardiac surgery 1st editionKluwer Academic 1993 317-33

10 Kronon MT Allen BS

Rahman S Wang T

Tayyab NA Bolling KS and

Ilbawi MN Reducingpostischemic reper-fusion

damage in neonates using a

terminal warm substrate-enriched blood cardioplegicreperfusate Ann Thorac Surg2000 70(3) 765-770

11 Modi P Suleiman MS

Reeves B Pawade A Parry

AJ Angelini GD and

Caputo M Myocardial

metabolic changes during ped-iatric cardiac surgery arando-mized study of 3cardioplegic techniques JThorac Cardiovasc Surg2004 128(1) 67-75

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Comparison of cardioprotective effects Hussein Sabri et al

28

12 Nomura F Forbess JM

and Mayer EJ Effects ofHot shot on recovery afterhypothermic ischemia in

neonatal lamb heart JCardiovasc Surg (Torino)2001 42(1) 1-7

13 Teoh KH Christakis GT

Weisel RD Fremes SE

Mickle DA Romaschin AD

Harding RS Ivanov J

Madonik MM Ross IM et

al Accelerated myocardial

metabolic recovery with

terminal warm bloodcardioplegia J ThoracCardiovasc Surg 1986 91(6)

888-95

14 Toyoda Y Yamaguchi M

Yoshimura N Oka S and

Okita Y Cardioprotectiveeffects and the mechanisms of

terminal warm bloodcardioplegia in pediatriccardiac surgery J ThoracCardiovasc Surg 2003 125

(6) 1242-51

15 Wernovsky G Wypij D

Jonas RA Mayer JE Jr

Hanley FL Hickey PR

Walsh AZ Chang AC

Castaneda AR NewburgerJW et al Postoperativecourse and hemodynamicprofile after the arterial

switch operation in neo-natesand infants A comparison of

low-flow cardiopulmonarybypass and circulatory arrestCirculation 1995 92(8) 2226-

35

16 Young JN Choy IO SilvaNK Obayashi DY and

Barkan HE Antegrade cold

blood cardioplegia is not

demonstrably advan-tageousover cold crystalloidcardioplegia in surgery forcongenital heart disease J

Thorac Cardiovasc Surg1997 114(6) 1002-9

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Comparison of cardioprotective effects Hussein Sabri et al

14

blood gas acid base andelectrolytes analysis to correctany change in the ventilationelectrolytes or acid base balance

of the patient Maintenance of anesthesia

Anesthesia was maintained by

isoflurane 02-04 in 50 oxygen

air mixture extra analgesia wasprovided by fentanyl 10microgkg-1 IVbefore sternotomy in incrementsPancuronium in a dose of002mgkg-1 IV was used as

increment for adequate muscle

relaxation Management of cardio-

pulmonary bypass Immediately

after anesthetic induction activatedclotting time (ACT) was measuredand used as a control Anti-coagulation was achieved byadministration of heparin sulphate

3mgkg-1 IV and adjusted tomaintain ACT more than 480seconds Priming of Cardiopul-monary bypass (CPB) circuit

consisted of ringer solution

manifold sodium bicarbonate andblood or plasma depending oninitial hematocrit CPB wasestablished between ascending

aortic and bicaval cannulation CPBwas instituted using non-pulsatileflow ranging between 100-150mlkg-1min-1 to maintain mean

arterial pressure between 40-60mmHg

At full flow of CBP mecha-nical ventilation was stopped and

the lungs remained collapsed atthe functional residual capacityModerate systemic hypothermiawas used [28degC-32degC] Alpha stat

strategy for pH management wasadopted Hematocrit was main-tained above 25

Protocol of myocardial pro-tection In control group (C) Myo-

cardial protection was achievedwith intermittent antegrade coldblood cardioplegia with topicalheart cooling in all patients

Cardioplegic solution of 20mLKg-1

of body weight was initially infusedinto the aortic root after applicationof aortic cross clamp to achieve

cardiac arrest with subsequent

doses every 20min Blood cardio-plegia was prepared by mixingoxygenated blood with hyper-kalemic crystalloid solution in 11ratio with sodium bicarbonate

added as buffer lidocaine as mem-brane stabilizer and cooled to 9degC

[Table 1] [Table 2]

In hot-shot group (HS) Cardio-

plegic regimen was the same withan additional 20mLKg-1 of body

weight of warm (35degC) bloodcardioplegia was infused into the

aortic root just before declamping ofthe aorta The composition ofterminal warm blood cardioplegiawas the same as the cold blood

cardioplegia other than tempera-ture

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

15

Table (1) Components added to crystalloid solution per liter

KCl 40 mmol L-1

NaHCO3 40 mmol L-1

Lidocaine 100 mg L-1

Table (2) Final composition of cardioplegia after mixing oxygenatedblood with hyperkalemic crystalloid solution in 11 ratio

pH 76

Hematocrit 17-22

K + 20 mmol L-1

Na+ 150 mmol L-1

Cl+ 150 mmol L-1

Ca2+ 2 mmol L-1

Osmolaritv 380 mOsm L-1

Weaning of cardiopul-

monary bypass After completion

of the surgical repair rewarming

was instituted Standard deairingmaneuvers were performed beforeremoval of the aortic cross-clamp

Ventricular distention during re-perfusion was avoided by regu-

lation of systemic venous return

and ventricular vent Electricaldefibrillation was applied to theheart if ventricular fibrillation

persisted Pacing the heart was

applied if there was second orthird degree heart block orintractable sinus bradycardia

Once optimal heart rate

electrolyte acid-base and tem-perature were achieved mechanicalventilation was resumed Afteroptimizing preload and afterload

CBP was gradually stopped If

systolic blood pressure was lowerthan 80 mm Hg despite centralvenous pressure above 10cm H2Odobutamine was our first choice

inotrope [dobutamine infusion

starting at a dose of 5-15microgkg-1 min-1] Epinephrine was our secondchoice when dobutamine alone was

ineffective [epinephrine infusionstarting at a dose of 50-250ngkg-1

min-1] Inotrope dose was titratedaccording to the hemodynamic andclinical state of the patient

At the end of bypass

protamine sulfate in a dose of15mg per 1mg heparin was usedto neutralize heparin effect The

chest was then closed in routine

fashion once meticulous hemos-tasis was achieved

Postoperative care Patient

admitted to pediatric cardiac sur-

gery intensive care unit Routinepostoperative management wasgiven to all patients Decision regar-ding ventilation and inotrope were

based on unit protocol hemody-

namic status and clinical judgment

Parameters of the study

Assessment of clinical outcomeIntraoperative and postoperative

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

17

O2 content CS oxygen content incoronary sinus blood sample

Myocardial lactate extraction

ratio was calculated according to

the following equation

Myocardial lactate extractionrate ratio= [lactate A - lactate CS] x100lactate A

Lactate A serum lactate concen-tration in arterial blood sample

Lactate CS serum lactate concen-

tration in coronary sinus bloodsample

Serum level of cardiac

troponin I (cTnI) Two millilitersof blood sample collected fromeach patient after induction of

anesthesia and at 4 8hrs afterdeclamping of the aorta Bloodsamples were centrifuged and

stored at -20deg until the completionof the study when thawed once

and assays were performed by a

laboratory technician blinded tothe clinical status of the patientor their inclusion in the studySerum concentration of cardiac

troponin I was determined with acommercially available enzyme-linked immunosorbent assay

(ELISA) kits cTnI ELISA-DRG

international Inc

Principle of the test Sample

was allowed to react with themicrotiter coated with monoclonalanti troponin I antibody (solid

phase) Monoclonal anti troponinI-enzyme (horseradish peroxidase)conjugate solution was added

resulting in the troponin I molec-

ules being sandwiched between

the solid phase and enzyme-linked antibodies

A solution of tetramethyl-benzidine (TMB) reagent was added

and incubated for 20 minutesresulting in the development of ablue color The color development

was stopped with the addition of 1Nhydrochloric acid (HCl) changing

the color to yellow The concen-tration of troponin I was directlyproportional to the color intensity ofthe test sample Absorbance was

measured spectrophotometrically

using Dade Behring Inc BEPreg

IIIat wavelength 450nm

Statistical analysis

All data were prospectively

collected coded tabulated thensubjected to statistical analysisusing SPSSreg for Windows version150 software packages Numericalvariables were presented as mean

and standard deviation (SD) while

categorical variables were presen-ted as number of cases and percent

Between-groups comparisons of

numerical variables were performedwith unpaired student-t test whilethose of categorical variables wereperformed by Fisher exact test orChi-square test as appropriate For

all tests P-value of less than 005

was considered statistically signifi-

cantResults

Patientsrsquo characteristics and

intraoperative data The demog-

raphic data and patients pathology

were comparable in both studygroups as shown in (Table 3)

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Comparison of cardioprotective effects Hussein Sabri et al

18

Intraoperative variables were alsocomparable in both study groups asshown in (Table 3) There was nosignificant difference as regards

cardiopulmonary bypass time (P

value was 0621) aortic cross-clamptime (P value was 0916) lowestoropharyngeal temperature (Pvalue was 0749)

Table 3 Patientsrsquo characteristics and intraoperative dataControl group

No =30

Hot-shot group

No =30P value

Age (month) 175 plusmn 56 181 plusmn 57 0716

Sex (MF) 1416 1614 0797

Weight (Kg) 141 plusmn 38 148 plusmn 42 0481

Pathology (n)

Acyanotic 17 19 ASD 6 7

VSD 7 9

CAVSD 4 3

Cyanotic 13 11

TOF 7 6

DORV- PS 6 5

CBP (min) 643plusmn 259 679plusmn 288 0621

Ao Cx (min) 378plusmn 169 382plusmn 171 0916

Oropharyngeal temp (degC) 306 plusmn 22 307 plusmn 20 0749

Mean plusmn SD MF male female ratio n number of patients ASD atrial septal defect

VSD ventricular septal defect CAVSD complete atrioventricular septal defect TOFtetralogy of Fallot DORV- PS double outlet right ventricle with pulmonary stenosis

CPB cardiopulmonary bypass Ao Cx aortic crossclamp P value is significant whenP lt 005 unpaired t test for age weight CBP Ao Cx and oropharyngeal temp

Fisherrsquos exact test for sex Chi-square test for pathology

Parameters of the study

Clinical outcome parameters

Intraoperative parametersThere was a significant difference

between both study groups after

declamping of the aorta Spon-taneous defibrillation into sinusrhythm occurred in 23 patients ofhot-shot group versus 10 patients of

control group (P value was 0002)Electrical defibrillation was requi-red in 7 patients of hotshot groupversus 20 patients of control group

(P value was 0002) (Table 4)

As regards requirement ofpacing to wean from cardio-pulmonary bypass there was no

significant difference between bothstudy groups Pacing was requiredin 5 patients of hot-shot groupversus 7 patients of control group (P

value was 0748) (Table 4)

As regards intraoperative

inotropes there was a significantdifference between both studygroups as regards number of

patients who required inotropes

for weaning of cardiopulmonarybypass Inotropes were requiredin 14 patients of hot-shot group

versus 24 patients of control group

(P value was 0015) (Table 4)

There was also a significantdifference between both groups as

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

19

regards inotropic score requiredfor weaning fromcardiopulmonary bypass Inotropescore was 44plusmn55 in hot-shot

group versus 105plusmn65 in controlgroup (P-value was lt0001)(Table 4)

Table 4 Intraoperative clinical outcome variablesControl

group

No =30

Hot-shot

group

No =30

P

value

Spontaneous defibrillation into sinusrhythm n ()

10 (333) 23 (767) 0002

Electrical defibrillation n () 20 (667) 7 (233) 0002

Requirement of pacing for weaning fromCBP n ()

7 (233) 5 (167) 0748

Requirement of intraoperative inotrope n

()24 (80) 14 (467) 0015

Inotrope score required for weaning from

CBP Mean plusmn SD 105plusmn

65 44plusmn

55 lt0001

n() Number (percentage) of patients Mean plusmnSD P-value is significant when Plt005 unpaired t

test for inotrope score P value is significant when P lt 005 Fisherrsquos exact test for spontaneous

defibrillation electrical defibrillation requirement of pacing and intraoperative inotrope

Postoperative parameters

There was a significant

difference between both studygroups as regards inotropes

required in the intensive careInotropes were required in 14

patients of hot-shot group versus24 patients of control group (Pvalue was 0015) Inotrope score

in the ICU was 754plusmn612 in hot-shot group versus 1225plusmn1032 incontrol group (P value was 0036)

Inotrope duration was 95plusmn72hrsin hot-shot group versus

149plusmn118hrs in control group (Pvalue was 0039) (Table 5)

As regards duration ofmechanical ventilation there was

no significant difference betweenboth study groups Duration ofmechanical ventilation was 67 plusmn 38

hrs in hot-shot group versus88plusmn44hrs in control group (Pvalue was 0053) (Table 5)

As regards duration of ICU

stay there was no significantdifference between both study

groups Duration of ICU stay was511plusmn188hrs in hot-shot groupversus 603plusmn231hrs in control

group (P-value was 0099) (Table

5)

There was no significantdifference between both study

groups as regards mortality Therewas no postoperative death in hot-shot group versus 3 postoperative

deaths in control group (P valuewas 0237) (Table 5)

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Comparison of cardioprotective effects Hussein Sabri et al

20

Table 5 Postoperative clinical outcome parametersControl

group

No =30

Hot-shot

group

No =30

P

value

Requirement of postoperative inotrope n () 24 (80) 14 (467) 0015

Inotrope score in ICU Meanplusmn SD 1225plusmn1032 754plusmn612 0036

Inotrope duration (h) Mean plusmn SD 149plusmn118 95plusmn72 0039

Duration of mechanical ventilation (h) Mean plusmn SD 88plusmn 44 67plusmn 38 0053

Duration of ICU stay (h) Mean plusmn SD 603 plusmn 231 511plusmn 188 0099

Mortality n () 3 (10) 0 (0) 0237

n () Number (percentage) of patients Mean plusmnSD P-value is significant when Plt005

unpaired t-test for inotrope score in ICU inotrope duration duration of mechanical Ventilation and duration of ICU stay P-value is significant when Plt005 Fisherrsquos exact test

for requirement of postoperative inotrope and mortality

Myocardial oxygen and lactate

extraction ratio As regards myo-

cardial oxygen extraction ratiothere was no significant differencebetween hot-shot group and

control group at the different

studied time intervals throughout

the initial sixty minutes ofreperfusion (P-value was gt005)(Table 6 Fig 1)

Table 6 Myocardial oxygen extraction ratio (MO2 ER)

Time interval after declamping of the aorta

Control

group

No =30

Hot-shot

group

No =30

P

value

M O2 ER immediately after declamping 529plusmn 62 512 plusmn 66 0308

M O2 ER 15 min after declamping 505plusmn 58 494 plusmn 61 0477

M O2 ER 30 min after declamping 492plusmn 55 480 plusmn 58 0414

M O2 ER 45 min after declamping 485plusmn 52 472 plusmn 55 0351

M O2 ER 60 min after declamping 476plusmn 51 468 plusmn 53 0554Mean plusmnSD P value is significant when P lt 005 unpaired t-test

983091983088

983091983093

983092983088

983092983093

983093983088

983093983093

983094983088

983088 983149983145983150 983089983093 983149983145983150 983091983088 983149983145983150 983092983093 983149983145983150 983094983088 983149983145983150

983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137

983117 983161 983151 983139 983137 983154 983140 983145 983137

983148 983151 983160 983161 983143 983141 983150 983141 983160 983156 983154 983137 983139 983156 983145 983151 983150 983154 983137 983156 983145 983151 983077 983139983151983150983156983154983151983148 983143983154983151983157983152

983144983151983156983085983155983144983151983156 983143983154983151983157983152

Fig 1 Myocardial oxygen extraction ratio Data are presented as mean Error bars represent

95 confidence interval

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

21

As regards myocardial lactateextraction ratio there was signi-ficant difference between hot-shotgroup and control group at the

different studied time intervals

throughout the initial sixtyminutes of reperfusion (P-valueswere 0027 0042 0024 lt0001lt0001 respectively) (Table 7

Fig 2)

Table 7 Myocardial lactate extraction ratio (M lactate ER)

Time interval after declamping of the aorta

Control

group

No =30

Hot-shot

group

No =30

P-

value

M lactate ER immediately after declamping -222plusmn 59 -190plusmn 50 0027

M lactate ER 15 min after declamping -136plusmn 50 -111plusmn 42 0042

M lactate ER 30 min after declamping -75plusmn 54 -44plusmn 49 0024

M lactate ER 45 min after declamping -48plusmn 40 00plusmn 46 lt0001

M lactate ER 60 min after declamping -26plusmn 34 59plusmn 41 lt0001

Mean plusmn SD P value is significant when Plt005 unpaired t-test

983085983091983088

983085983090983093

983085983090983088

983085983089983093

983085983089983088

983085983093

983088

983093

983089983088

983089983093

983090983088

983088 983149983145983150 983089983093 983149983145983150 983091983088 983149983145983150 983092983093 983149983145983150 983094983088 983149983145983150

983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137

983117 983161 983151 983139 983137 983154 983140 983145 983137 983148 983148 983137 983139 983156 983137 983156 983141 983141 983160 983156 983154 983137 983139 983156

983145 983151 983150 983154 983137 983156 983145 983151 983077

983139983151983150983156983154983151983148 983143983154983151983157983152

983144983151983156983085983155983144983151983156 983143983154983151983157983152

Fig 2 Myocardial lactate extraction ratio Data are presented as mean Error bars

represent 95 confidence interval P-value is significant when Plt005

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Comparison of cardioprotective effects Hussein Sabri et al

22

Serum level of cardiac troponinI (cTnI) There was no significantdifference between both studygroups as regards baseline values of

serum troponin I (P-value was0146) There was significantdifference between both study

groups in serum troponin I level at4 and 8 hours after declamping of

the aorta Serum troponin I level at

4 hours after declamping was132plusmn80ngml in hot-shot groupversus 313plusmn231ngml in controlgroup (P value was lt0001) Serum

troponin I level at 8 hours afterdeclamping was 100plusmn58ngml inhot-shot group versus 191plusmn115ngml in control group (P value waslt0001) (Table 8 Fig 3)

Table 8 Serum level of cardiac troponin I (cTnI)Control

group

No =30

Hot-shot

group

No =30

P

value

Baseline (ngml) 08plusmn

04 07plusmn

04 01464 hrs after declamping of the aorta (ngml) 313plusmn 231 132 plusmn 80 lt0001

8 hrs after declamping of the aorta (ngml) 191plusmn 115 100 plusmn 58 lt0001

Mean plusmn SD P-value is significant when P lt 005 unpaired t test

983088

983093

983089983088

983089983093

983090983088

983090983093

983091983088

983091983093

983092983088

983092983093

983138983137983155983141983148983145983150983141 983092 983144983154983155 983096 983144983154983155

983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137

983124 983154 983151 983152 983151 983150 983145 983150 983113 983080 983150 983143 983087 983149 983148 983081

983139983151983150983156983154983151983148 983143983154983151983157983152

983144983151983156983085983155983144983151983156 983143983154983151983157983152

Fig 3 Serum level of cardiac troponin I (cTnI) Data are presented as mean Errorbars represent 95 confidence interval P value is significant when P lt 005

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

23

Discussion

Low cardiac output aftersurgically induced ischemia andreperfusion continues to be a major

contributor to morbidity andmortality after pediatric cardiacsurgery and in more than 50 of

cases has been attributed toinadequate myocardial protection(Bull et al 1984 Hammon

1995)

Careful control of theconditions of reperfusion and the

composition of the reperfusate can

optimize postischemic recovery ofmyocardial function (Follette et

al 1981 Allen et al 1986)

The current study wasdesigned to evaluate the cardio-protective effect of using inter-mittent antegrade cold bloodcardioplegia versus intermittent

cold blood cardioplegia with ter-minal warm blood cardioplegia

(hot-shot) in pediatric cardiacpatients

The result of the current

study demonstrated significantdecrease in blood pressure at 5and 15 minutes interval in thecontrol group compared with the

hot-shot group after weaning ofthe cardiopulmonary bypass

Intermittent cold blood

cardioplegia with terminal warmblood cardioplegia offers favorable

effect on the clinical outcomeparameters This was demon-strated in this study as asignificant higher percentage ofspontaneous defibrillation into

sinus rhythm in hot-shot group

than control group (767 versus333 respectively)

The percentage of patientsrequiring inotropic support after

weaning from cardiopulmonarybypass was significantly higher incontrol group than hot-shot group

(80 versus 467 respectively)

By adopting the inotropic scoredescribed by Wernovsky et al

(1995) the level of inotropic

support was significantly lower inhot-shot group than control group

(44plusmn55 versus 105plusmn65 respec-

tively)

The improved clinical outcomerevealed the role of intermittent

cold blood cardioplegia withterminal warm blood cardioplegia inenhancement of myocardialprotection which was manifested asa reduction in myocardial arrhyth-

mia associated with ischemiareperfusion and a better myocardial

functionThe myocardial protective effect

of terminal warm blood cardioplegia

extended into the postoperativeperiod This was manifested as asignificant higher percentage ofpatients in control group than hot-

shot group who required inotropicsupport in the intensive care (80

versus 467 respectively) The

maximum dose of inotropic support(calculated by a modification of

inotropic score) was significantlyhigher in control group than hot-shot group (1225plusmn1032 versus754plusmn612 respectively) Theduration of inotropic support was

significantly higher in control group

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Comparison of cardioprotective effects Hussein Sabri et al

24

than hot-shot group (149plusmn118versus 95plusmn72 respectively)

In the postoperative periodresults were comparable as

regards duration of mechanicalventilation and stay in theintensive care unit in addition to

comparable mortality rate

Myocardial oxygen extraction

ratio reflects balance betweenmyocardial oxygen supply anddemand Myocardial oxygenextraction ratio was similar

between the two studied groups

This similarity may reflect theaerobic metabolic state of the

myocardium provided by the coldblood cardioplegia in both groups

Lactate release from theischemic myocytes is considered asa reflection of anaerobic metabolism(Krause et al 1993)

A negative myocardial lactateextraction ratio indicates that

amount of lactate productionthrough anaerobic glycolysis washigher than the amount of lactate

consumption for aerobic energy pro-duction with continuing anaerobicmetabolism and impairment ofnormal aerobic energy production

While a positive myocardial

lactate extraction ratio indicatesthat amount of lactate production

through anaerobic glycolysis wasless than the amount of lactate

consumption for aerobic energyproduction and that myocardiumstarts to use lactate as a substratevia oxidative phosphorylation

Myocardial lactate extractionratio in control group stayednegative value all through the sixtyminutes of studied period which

indicates impairment of aerobicmyocardial metabolism during thisperiod In hot-shot group myo-cardial lactate extraction ratioremained negative value till 45min

after declamping of the aorta when

it becomes a positive value

This point is considered a turnfrom anaerobic to aerobic meta-

bolism and it resembles the equilib-

rium between lactate consumptionand production At this point themyocardium starts to use lactate as

a substrate via oxidative phosphor-rylation (Krause et al 1993)

The results of this studydemonstrate the recovery of aerobicmetabolism afforded by inter-

mittent cold blood cardioplegia withterminal warm blood cardioplegiaTroponin I is a myocyte-contractileapparatus protein released follo-

wing myocardial damage Troponin

I Level is considered sensitivemarker of myocardial injuryassociated with cardiac surgery

(Immer et al 1998)

In this study we demonstrated

a significant increase in post-operative troponin I at 4 8 hoursafter declamping of the aorta in

control group compared to hot-shotgroup (P value was lt0001) Thisreflects the beneficial effect of warmcardioplegic reperfusion on myo-cardial outcome in reducing themyocardial damage following

ischemiareperfusion injury

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

25

In this study the composition ofterminal warm blood cardioplegiawas made to resemble the compo-sition of cold blood cardioplegia

used The point was to provide asolution with adequate potassiumconcentration to produce electro-mechanical arrest during reper-fusion This solution differs from the

conventional blood reperfusate in

presence of high potassiumconcentration (20mmolL-1) ahigher pH and a higher osmolarity

Thus cardioprotective effect ofterminal warm blood cardioplegia is

expected to be achieved byprolongation of electromechanicalarrest which reduces the energy

demands and counteracting tissueacidosis and edema therefore it

reduces the myocardial injury bypreservation and resynthesis ofhigh energy phosphates

There were small number ofclinical studies that have

examined specific myocardialprotection strategy in pediatric

population Utilizing an isolatedblood perfused neonatal heartpreparation Nomura et al

(2001) assessed the effects of

terminal warm blood cardioplegiaterminal warm oxygenated crys-talloid cardioplegia in comparisonwith conventional reperfusion(without any kind of terminal

cardioplegia) through assessmentrecovery of left ventricularfunction They demonstrated that

reperfusion with either terminalwarm blood cardioplegia or ter-

minal warm oxygenated crys-talloid cardioplegia resulted in

better recovery of myocardialfunction with slightly betterfunction in terminal warm bloodcardioplegia

In a clinically relevant intactanimal model that simulated theclinical condition of hypoxic

neonatal myocardium exposed toischemic stress Kronon et al

(2000) investigated the cardio-

protective effects of terminalwarm blood cardioplegic reper-fusion versus conventional reper-

fusion through assessment reco-

very of left ventricular systolicfunction and diastolic complianceThey showed that A warm cardio-

plegic reperfusion helps reduce

the reperfusion injury resultingin improved myocardial functionand metabolic recovery in hypoxicneonatal myocardium

Toyoda et al (2003) examined

the cardioprotective effect ofterminal warm blood cardioplegia inpediatric cardiac patients Blood

cardioplegia solution was composed

by mixing a hyperkalemic solutionwith oxygenated blood in 12dilutions with temperature 9oCThe terminal warm blood

cardioplegia had a finalconcentration of potassium 18mmolL-1 The results of Toyoda et alshowed beneficial effect of terminal

warm blood cardioplegia inreduction of myo-cardial injury Inagreement with Toyoda the

protocol of cardioplegiaadministered is almost similar asregard the concentration of pota-

ssium in terminal warm bloodcardioplegia (20mmolL-1) in 11

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

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Comparison of cardioprotective effects Hussein Sabri et al

26

dilution (1 crystalloid 1 blood) withsimilar result in myocardial pro-tection and improvement in aerobicenergy metabolism As a marker of

myocardial necrosis the currentstudy used troponin I whichprovides comparable information astroponin T used in the study ofToyoda

The current study is inagreement with Modi et al

(2004) who compared the use of

crystalloid cardioplegia cold blood

cardioplegia and cold blood

cardioplegia with hot-shot incyanotic and acyanotic pediatricpatients undergoing surgical

correction The efficacy of the 3

techniques was assessed byexamination right ventricularbiopsy specimen before and afterreperfusion analysis of cellular

metabolites and assessment oftroponin I level Their resultdemonstrated that for cyanotic

patients blood cardioplegia withhot-shot reduced metabolic injury

compared with cold crystalloidcardioplegia They also showed

that cold blood cardioplegia wason its own better than crystalloid

but not as good as cold bloodcardioplegia with hot-shot

Young et al (1997) failed to

demonstrate statistical advantage

for blood cardioplegia over crys-talloid cardioplegia in surgery forcongenital heart The most impor-

tant aspect of the study of Younget al is that no obvious benefitcan be anticipated by use of blood

cardioplegia in congenital heartsurgery when only antegrade

hypothermia dosing technique isused The integrated cardioplegicapproach using warm cold ante-grade and retrograde technique

with substrate enrichment may bebeneficial for pediatric population

As conclusion the result of

the current study showed that theuse of cardioplegia with hot-shot

provides the criteria that mayimprove myocardial protectionand reduce myocardial injury inpediatric population

These criteria include warm

blood accelerates recovery oftemperature-dependent enzymatic

and metabolic function highpotassium concentration prolongs

electromechanical arrest to decreaseenergy demands alkaloid solutionwhich counteracts tissue acidosisand high osmolarity which coun-teracts tissue edema

References

1 Allen BS Okamoto F

Buckberg GD Bugyi H

Young H Leaf J

Beyersdorf F Sjostrand F

and Maloney JV Jr

Studies of controlledreperfusion after ischemiaXV Immediate functional

recovery after six hours of

regional ischemia by careful

control of conditions ofreperfusion and compositionof reperfusate J Thorac

Cardiovasc Surg 1986 92(3Pt 2) 621-35

2 Allen BS Current Conceptsin Pediatric Myocardial

Protection In Salerno TA and

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

27

Ricci M (editors) MyocardialProtection 1st editionBlackwell publishing 2004207-29

3 Allen BS Pediatricmyocardial protection acardioplegic stra-tegy is the

solution Semin Thorac

Cardiovasc Surg Pediatr CardSurg Annu 2004 7 141-54

4 Bull C Cooper J and

Stark J Cardioplegicprotection of the childrsquos

heart J Thorac Cardio-vasc

Surg 1984 88(2) 287-93

5 Caputo M Dihmis WC

Bryan AJ Suleiman MS

and Angelini GD Warmblood hyperkalaemicreperfusion (hot shot)prevents myocardial substratederangement in patients

undergoing coronary arterybypass surgery Eur J

Cardiothorac Surg 199813(5) 559-64

6 Follette DM Fey K

Buckberg GD Helly JJ Jr

Steed DL Foglia RP and

Maloney JV Jr Reducingpostischemic damage by

temporary modifi-cation ofreperfusate calcium

potassium pH and

osmolarity J ThoracCardiovasc Surg 1981 82 (2)

221-38

7 Hammon JW Jr Myocardialprotection in the immatureheart Ann Thorac Surg 1995

60 (3) 839-842

8 Immer FF Stocker FP

Seiler AM Pfammatter JP

Printzen G and Carrel TP

Comparison of troponin-I and

troponin-T after pediatriccardiovascular opera-tion

Ann Thorac Surg 1998 66 (6)2073-7

9 Krause EG Pfeiffer D

Wollen-berger U and

Wollert HG Lactatemonitoring during and aftercardiopulmonary bypass an

approach implicating a peri-

operative measure for cardiacenergy metabolism In PiperHM Preusse CJ (editors)

Ischemia-reperfusion in

cardiac surgery 1st editionKluwer Academic 1993 317-33

10 Kronon MT Allen BS

Rahman S Wang T

Tayyab NA Bolling KS and

Ilbawi MN Reducingpostischemic reper-fusion

damage in neonates using a

terminal warm substrate-enriched blood cardioplegicreperfusate Ann Thorac Surg2000 70(3) 765-770

11 Modi P Suleiman MS

Reeves B Pawade A Parry

AJ Angelini GD and

Caputo M Myocardial

metabolic changes during ped-iatric cardiac surgery arando-mized study of 3cardioplegic techniques JThorac Cardiovasc Surg2004 128(1) 67-75

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

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Comparison of cardioprotective effects Hussein Sabri et al

28

12 Nomura F Forbess JM

and Mayer EJ Effects ofHot shot on recovery afterhypothermic ischemia in

neonatal lamb heart JCardiovasc Surg (Torino)2001 42(1) 1-7

13 Teoh KH Christakis GT

Weisel RD Fremes SE

Mickle DA Romaschin AD

Harding RS Ivanov J

Madonik MM Ross IM et

al Accelerated myocardial

metabolic recovery with

terminal warm bloodcardioplegia J ThoracCardiovasc Surg 1986 91(6)

888-95

14 Toyoda Y Yamaguchi M

Yoshimura N Oka S and

Okita Y Cardioprotectiveeffects and the mechanisms of

terminal warm bloodcardioplegia in pediatriccardiac surgery J ThoracCardiovasc Surg 2003 125

(6) 1242-51

15 Wernovsky G Wypij D

Jonas RA Mayer JE Jr

Hanley FL Hickey PR

Walsh AZ Chang AC

Castaneda AR NewburgerJW et al Postoperativecourse and hemodynamicprofile after the arterial

switch operation in neo-natesand infants A comparison of

low-flow cardiopulmonarybypass and circulatory arrestCirculation 1995 92(8) 2226-

35

16 Young JN Choy IO SilvaNK Obayashi DY and

Barkan HE Antegrade cold

blood cardioplegia is not

demonstrably advan-tageousover cold crystalloidcardioplegia in surgery forcongenital heart disease J

Thorac Cardiovasc Surg1997 114(6) 1002-9

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

15

Table (1) Components added to crystalloid solution per liter

KCl 40 mmol L-1

NaHCO3 40 mmol L-1

Lidocaine 100 mg L-1

Table (2) Final composition of cardioplegia after mixing oxygenatedblood with hyperkalemic crystalloid solution in 11 ratio

pH 76

Hematocrit 17-22

K + 20 mmol L-1

Na+ 150 mmol L-1

Cl+ 150 mmol L-1

Ca2+ 2 mmol L-1

Osmolaritv 380 mOsm L-1

Weaning of cardiopul-

monary bypass After completion

of the surgical repair rewarming

was instituted Standard deairingmaneuvers were performed beforeremoval of the aortic cross-clamp

Ventricular distention during re-perfusion was avoided by regu-

lation of systemic venous return

and ventricular vent Electricaldefibrillation was applied to theheart if ventricular fibrillation

persisted Pacing the heart was

applied if there was second orthird degree heart block orintractable sinus bradycardia

Once optimal heart rate

electrolyte acid-base and tem-perature were achieved mechanicalventilation was resumed Afteroptimizing preload and afterload

CBP was gradually stopped If

systolic blood pressure was lowerthan 80 mm Hg despite centralvenous pressure above 10cm H2Odobutamine was our first choice

inotrope [dobutamine infusion

starting at a dose of 5-15microgkg-1 min-1] Epinephrine was our secondchoice when dobutamine alone was

ineffective [epinephrine infusionstarting at a dose of 50-250ngkg-1

min-1] Inotrope dose was titratedaccording to the hemodynamic andclinical state of the patient

At the end of bypass

protamine sulfate in a dose of15mg per 1mg heparin was usedto neutralize heparin effect The

chest was then closed in routine

fashion once meticulous hemos-tasis was achieved

Postoperative care Patient

admitted to pediatric cardiac sur-

gery intensive care unit Routinepostoperative management wasgiven to all patients Decision regar-ding ventilation and inotrope were

based on unit protocol hemody-

namic status and clinical judgment

Parameters of the study

Assessment of clinical outcomeIntraoperative and postoperative

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

17

O2 content CS oxygen content incoronary sinus blood sample

Myocardial lactate extraction

ratio was calculated according to

the following equation

Myocardial lactate extractionrate ratio= [lactate A - lactate CS] x100lactate A

Lactate A serum lactate concen-tration in arterial blood sample

Lactate CS serum lactate concen-

tration in coronary sinus bloodsample

Serum level of cardiac

troponin I (cTnI) Two millilitersof blood sample collected fromeach patient after induction of

anesthesia and at 4 8hrs afterdeclamping of the aorta Bloodsamples were centrifuged and

stored at -20deg until the completionof the study when thawed once

and assays were performed by a

laboratory technician blinded tothe clinical status of the patientor their inclusion in the studySerum concentration of cardiac

troponin I was determined with acommercially available enzyme-linked immunosorbent assay

(ELISA) kits cTnI ELISA-DRG

international Inc

Principle of the test Sample

was allowed to react with themicrotiter coated with monoclonalanti troponin I antibody (solid

phase) Monoclonal anti troponinI-enzyme (horseradish peroxidase)conjugate solution was added

resulting in the troponin I molec-

ules being sandwiched between

the solid phase and enzyme-linked antibodies

A solution of tetramethyl-benzidine (TMB) reagent was added

and incubated for 20 minutesresulting in the development of ablue color The color development

was stopped with the addition of 1Nhydrochloric acid (HCl) changing

the color to yellow The concen-tration of troponin I was directlyproportional to the color intensity ofthe test sample Absorbance was

measured spectrophotometrically

using Dade Behring Inc BEPreg

IIIat wavelength 450nm

Statistical analysis

All data were prospectively

collected coded tabulated thensubjected to statistical analysisusing SPSSreg for Windows version150 software packages Numericalvariables were presented as mean

and standard deviation (SD) while

categorical variables were presen-ted as number of cases and percent

Between-groups comparisons of

numerical variables were performedwith unpaired student-t test whilethose of categorical variables wereperformed by Fisher exact test orChi-square test as appropriate For

all tests P-value of less than 005

was considered statistically signifi-

cantResults

Patientsrsquo characteristics and

intraoperative data The demog-

raphic data and patients pathology

were comparable in both studygroups as shown in (Table 3)

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Comparison of cardioprotective effects Hussein Sabri et al

18

Intraoperative variables were alsocomparable in both study groups asshown in (Table 3) There was nosignificant difference as regards

cardiopulmonary bypass time (P

value was 0621) aortic cross-clamptime (P value was 0916) lowestoropharyngeal temperature (Pvalue was 0749)

Table 3 Patientsrsquo characteristics and intraoperative dataControl group

No =30

Hot-shot group

No =30P value

Age (month) 175 plusmn 56 181 plusmn 57 0716

Sex (MF) 1416 1614 0797

Weight (Kg) 141 plusmn 38 148 plusmn 42 0481

Pathology (n)

Acyanotic 17 19 ASD 6 7

VSD 7 9

CAVSD 4 3

Cyanotic 13 11

TOF 7 6

DORV- PS 6 5

CBP (min) 643plusmn 259 679plusmn 288 0621

Ao Cx (min) 378plusmn 169 382plusmn 171 0916

Oropharyngeal temp (degC) 306 plusmn 22 307 plusmn 20 0749

Mean plusmn SD MF male female ratio n number of patients ASD atrial septal defect

VSD ventricular septal defect CAVSD complete atrioventricular septal defect TOFtetralogy of Fallot DORV- PS double outlet right ventricle with pulmonary stenosis

CPB cardiopulmonary bypass Ao Cx aortic crossclamp P value is significant whenP lt 005 unpaired t test for age weight CBP Ao Cx and oropharyngeal temp

Fisherrsquos exact test for sex Chi-square test for pathology

Parameters of the study

Clinical outcome parameters

Intraoperative parametersThere was a significant difference

between both study groups after

declamping of the aorta Spon-taneous defibrillation into sinusrhythm occurred in 23 patients ofhot-shot group versus 10 patients of

control group (P value was 0002)Electrical defibrillation was requi-red in 7 patients of hotshot groupversus 20 patients of control group

(P value was 0002) (Table 4)

As regards requirement ofpacing to wean from cardio-pulmonary bypass there was no

significant difference between bothstudy groups Pacing was requiredin 5 patients of hot-shot groupversus 7 patients of control group (P

value was 0748) (Table 4)

As regards intraoperative

inotropes there was a significantdifference between both studygroups as regards number of

patients who required inotropes

for weaning of cardiopulmonarybypass Inotropes were requiredin 14 patients of hot-shot group

versus 24 patients of control group

(P value was 0015) (Table 4)

There was also a significantdifference between both groups as

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

19

regards inotropic score requiredfor weaning fromcardiopulmonary bypass Inotropescore was 44plusmn55 in hot-shot

group versus 105plusmn65 in controlgroup (P-value was lt0001)(Table 4)

Table 4 Intraoperative clinical outcome variablesControl

group

No =30

Hot-shot

group

No =30

P

value

Spontaneous defibrillation into sinusrhythm n ()

10 (333) 23 (767) 0002

Electrical defibrillation n () 20 (667) 7 (233) 0002

Requirement of pacing for weaning fromCBP n ()

7 (233) 5 (167) 0748

Requirement of intraoperative inotrope n

()24 (80) 14 (467) 0015

Inotrope score required for weaning from

CBP Mean plusmn SD 105plusmn

65 44plusmn

55 lt0001

n() Number (percentage) of patients Mean plusmnSD P-value is significant when Plt005 unpaired t

test for inotrope score P value is significant when P lt 005 Fisherrsquos exact test for spontaneous

defibrillation electrical defibrillation requirement of pacing and intraoperative inotrope

Postoperative parameters

There was a significant

difference between both studygroups as regards inotropes

required in the intensive careInotropes were required in 14

patients of hot-shot group versus24 patients of control group (Pvalue was 0015) Inotrope score

in the ICU was 754plusmn612 in hot-shot group versus 1225plusmn1032 incontrol group (P value was 0036)

Inotrope duration was 95plusmn72hrsin hot-shot group versus

149plusmn118hrs in control group (Pvalue was 0039) (Table 5)

As regards duration ofmechanical ventilation there was

no significant difference betweenboth study groups Duration ofmechanical ventilation was 67 plusmn 38

hrs in hot-shot group versus88plusmn44hrs in control group (Pvalue was 0053) (Table 5)

As regards duration of ICU

stay there was no significantdifference between both study

groups Duration of ICU stay was511plusmn188hrs in hot-shot groupversus 603plusmn231hrs in control

group (P-value was 0099) (Table

5)

There was no significantdifference between both study

groups as regards mortality Therewas no postoperative death in hot-shot group versus 3 postoperative

deaths in control group (P valuewas 0237) (Table 5)

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Comparison of cardioprotective effects Hussein Sabri et al

20

Table 5 Postoperative clinical outcome parametersControl

group

No =30

Hot-shot

group

No =30

P

value

Requirement of postoperative inotrope n () 24 (80) 14 (467) 0015

Inotrope score in ICU Meanplusmn SD 1225plusmn1032 754plusmn612 0036

Inotrope duration (h) Mean plusmn SD 149plusmn118 95plusmn72 0039

Duration of mechanical ventilation (h) Mean plusmn SD 88plusmn 44 67plusmn 38 0053

Duration of ICU stay (h) Mean plusmn SD 603 plusmn 231 511plusmn 188 0099

Mortality n () 3 (10) 0 (0) 0237

n () Number (percentage) of patients Mean plusmnSD P-value is significant when Plt005

unpaired t-test for inotrope score in ICU inotrope duration duration of mechanical Ventilation and duration of ICU stay P-value is significant when Plt005 Fisherrsquos exact test

for requirement of postoperative inotrope and mortality

Myocardial oxygen and lactate

extraction ratio As regards myo-

cardial oxygen extraction ratiothere was no significant differencebetween hot-shot group and

control group at the different

studied time intervals throughout

the initial sixty minutes ofreperfusion (P-value was gt005)(Table 6 Fig 1)

Table 6 Myocardial oxygen extraction ratio (MO2 ER)

Time interval after declamping of the aorta

Control

group

No =30

Hot-shot

group

No =30

P

value

M O2 ER immediately after declamping 529plusmn 62 512 plusmn 66 0308

M O2 ER 15 min after declamping 505plusmn 58 494 plusmn 61 0477

M O2 ER 30 min after declamping 492plusmn 55 480 plusmn 58 0414

M O2 ER 45 min after declamping 485plusmn 52 472 plusmn 55 0351

M O2 ER 60 min after declamping 476plusmn 51 468 plusmn 53 0554Mean plusmnSD P value is significant when P lt 005 unpaired t-test

983091983088

983091983093

983092983088

983092983093

983093983088

983093983093

983094983088

983088 983149983145983150 983089983093 983149983145983150 983091983088 983149983145983150 983092983093 983149983145983150 983094983088 983149983145983150

983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137

983117 983161 983151 983139 983137 983154 983140 983145 983137

983148 983151 983160 983161 983143 983141 983150 983141 983160 983156 983154 983137 983139 983156 983145 983151 983150 983154 983137 983156 983145 983151 983077 983139983151983150983156983154983151983148 983143983154983151983157983152

983144983151983156983085983155983144983151983156 983143983154983151983157983152

Fig 1 Myocardial oxygen extraction ratio Data are presented as mean Error bars represent

95 confidence interval

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

21

As regards myocardial lactateextraction ratio there was signi-ficant difference between hot-shotgroup and control group at the

different studied time intervals

throughout the initial sixtyminutes of reperfusion (P-valueswere 0027 0042 0024 lt0001lt0001 respectively) (Table 7

Fig 2)

Table 7 Myocardial lactate extraction ratio (M lactate ER)

Time interval after declamping of the aorta

Control

group

No =30

Hot-shot

group

No =30

P-

value

M lactate ER immediately after declamping -222plusmn 59 -190plusmn 50 0027

M lactate ER 15 min after declamping -136plusmn 50 -111plusmn 42 0042

M lactate ER 30 min after declamping -75plusmn 54 -44plusmn 49 0024

M lactate ER 45 min after declamping -48plusmn 40 00plusmn 46 lt0001

M lactate ER 60 min after declamping -26plusmn 34 59plusmn 41 lt0001

Mean plusmn SD P value is significant when Plt005 unpaired t-test

983085983091983088

983085983090983093

983085983090983088

983085983089983093

983085983089983088

983085983093

983088

983093

983089983088

983089983093

983090983088

983088 983149983145983150 983089983093 983149983145983150 983091983088 983149983145983150 983092983093 983149983145983150 983094983088 983149983145983150

983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137

983117 983161 983151 983139 983137 983154 983140 983145 983137 983148 983148 983137 983139 983156 983137 983156 983141 983141 983160 983156 983154 983137 983139 983156

983145 983151 983150 983154 983137 983156 983145 983151 983077

983139983151983150983156983154983151983148 983143983154983151983157983152

983144983151983156983085983155983144983151983156 983143983154983151983157983152

Fig 2 Myocardial lactate extraction ratio Data are presented as mean Error bars

represent 95 confidence interval P-value is significant when Plt005

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

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Comparison of cardioprotective effects Hussein Sabri et al

22

Serum level of cardiac troponinI (cTnI) There was no significantdifference between both studygroups as regards baseline values of

serum troponin I (P-value was0146) There was significantdifference between both study

groups in serum troponin I level at4 and 8 hours after declamping of

the aorta Serum troponin I level at

4 hours after declamping was132plusmn80ngml in hot-shot groupversus 313plusmn231ngml in controlgroup (P value was lt0001) Serum

troponin I level at 8 hours afterdeclamping was 100plusmn58ngml inhot-shot group versus 191plusmn115ngml in control group (P value waslt0001) (Table 8 Fig 3)

Table 8 Serum level of cardiac troponin I (cTnI)Control

group

No =30

Hot-shot

group

No =30

P

value

Baseline (ngml) 08plusmn

04 07plusmn

04 01464 hrs after declamping of the aorta (ngml) 313plusmn 231 132 plusmn 80 lt0001

8 hrs after declamping of the aorta (ngml) 191plusmn 115 100 plusmn 58 lt0001

Mean plusmn SD P-value is significant when P lt 005 unpaired t test

983088

983093

983089983088

983089983093

983090983088

983090983093

983091983088

983091983093

983092983088

983092983093

983138983137983155983141983148983145983150983141 983092 983144983154983155 983096 983144983154983155

983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137

983124 983154 983151 983152 983151 983150 983145 983150 983113 983080 983150 983143 983087 983149 983148 983081

983139983151983150983156983154983151983148 983143983154983151983157983152

983144983151983156983085983155983144983151983156 983143983154983151983157983152

Fig 3 Serum level of cardiac troponin I (cTnI) Data are presented as mean Errorbars represent 95 confidence interval P value is significant when P lt 005

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

23

Discussion

Low cardiac output aftersurgically induced ischemia andreperfusion continues to be a major

contributor to morbidity andmortality after pediatric cardiacsurgery and in more than 50 of

cases has been attributed toinadequate myocardial protection(Bull et al 1984 Hammon

1995)

Careful control of theconditions of reperfusion and the

composition of the reperfusate can

optimize postischemic recovery ofmyocardial function (Follette et

al 1981 Allen et al 1986)

The current study wasdesigned to evaluate the cardio-protective effect of using inter-mittent antegrade cold bloodcardioplegia versus intermittent

cold blood cardioplegia with ter-minal warm blood cardioplegia

(hot-shot) in pediatric cardiacpatients

The result of the current

study demonstrated significantdecrease in blood pressure at 5and 15 minutes interval in thecontrol group compared with the

hot-shot group after weaning ofthe cardiopulmonary bypass

Intermittent cold blood

cardioplegia with terminal warmblood cardioplegia offers favorable

effect on the clinical outcomeparameters This was demon-strated in this study as asignificant higher percentage ofspontaneous defibrillation into

sinus rhythm in hot-shot group

than control group (767 versus333 respectively)

The percentage of patientsrequiring inotropic support after

weaning from cardiopulmonarybypass was significantly higher incontrol group than hot-shot group

(80 versus 467 respectively)

By adopting the inotropic scoredescribed by Wernovsky et al

(1995) the level of inotropic

support was significantly lower inhot-shot group than control group

(44plusmn55 versus 105plusmn65 respec-

tively)

The improved clinical outcomerevealed the role of intermittent

cold blood cardioplegia withterminal warm blood cardioplegia inenhancement of myocardialprotection which was manifested asa reduction in myocardial arrhyth-

mia associated with ischemiareperfusion and a better myocardial

functionThe myocardial protective effect

of terminal warm blood cardioplegia

extended into the postoperativeperiod This was manifested as asignificant higher percentage ofpatients in control group than hot-

shot group who required inotropicsupport in the intensive care (80

versus 467 respectively) The

maximum dose of inotropic support(calculated by a modification of

inotropic score) was significantlyhigher in control group than hot-shot group (1225plusmn1032 versus754plusmn612 respectively) Theduration of inotropic support was

significantly higher in control group

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

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Comparison of cardioprotective effects Hussein Sabri et al

24

than hot-shot group (149plusmn118versus 95plusmn72 respectively)

In the postoperative periodresults were comparable as

regards duration of mechanicalventilation and stay in theintensive care unit in addition to

comparable mortality rate

Myocardial oxygen extraction

ratio reflects balance betweenmyocardial oxygen supply anddemand Myocardial oxygenextraction ratio was similar

between the two studied groups

This similarity may reflect theaerobic metabolic state of the

myocardium provided by the coldblood cardioplegia in both groups

Lactate release from theischemic myocytes is considered asa reflection of anaerobic metabolism(Krause et al 1993)

A negative myocardial lactateextraction ratio indicates that

amount of lactate productionthrough anaerobic glycolysis washigher than the amount of lactate

consumption for aerobic energy pro-duction with continuing anaerobicmetabolism and impairment ofnormal aerobic energy production

While a positive myocardial

lactate extraction ratio indicatesthat amount of lactate production

through anaerobic glycolysis wasless than the amount of lactate

consumption for aerobic energyproduction and that myocardiumstarts to use lactate as a substratevia oxidative phosphorylation

Myocardial lactate extractionratio in control group stayednegative value all through the sixtyminutes of studied period which

indicates impairment of aerobicmyocardial metabolism during thisperiod In hot-shot group myo-cardial lactate extraction ratioremained negative value till 45min

after declamping of the aorta when

it becomes a positive value

This point is considered a turnfrom anaerobic to aerobic meta-

bolism and it resembles the equilib-

rium between lactate consumptionand production At this point themyocardium starts to use lactate as

a substrate via oxidative phosphor-rylation (Krause et al 1993)

The results of this studydemonstrate the recovery of aerobicmetabolism afforded by inter-

mittent cold blood cardioplegia withterminal warm blood cardioplegiaTroponin I is a myocyte-contractileapparatus protein released follo-

wing myocardial damage Troponin

I Level is considered sensitivemarker of myocardial injuryassociated with cardiac surgery

(Immer et al 1998)

In this study we demonstrated

a significant increase in post-operative troponin I at 4 8 hoursafter declamping of the aorta in

control group compared to hot-shotgroup (P value was lt0001) Thisreflects the beneficial effect of warmcardioplegic reperfusion on myo-cardial outcome in reducing themyocardial damage following

ischemiareperfusion injury

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

25

In this study the composition ofterminal warm blood cardioplegiawas made to resemble the compo-sition of cold blood cardioplegia

used The point was to provide asolution with adequate potassiumconcentration to produce electro-mechanical arrest during reper-fusion This solution differs from the

conventional blood reperfusate in

presence of high potassiumconcentration (20mmolL-1) ahigher pH and a higher osmolarity

Thus cardioprotective effect ofterminal warm blood cardioplegia is

expected to be achieved byprolongation of electromechanicalarrest which reduces the energy

demands and counteracting tissueacidosis and edema therefore it

reduces the myocardial injury bypreservation and resynthesis ofhigh energy phosphates

There were small number ofclinical studies that have

examined specific myocardialprotection strategy in pediatric

population Utilizing an isolatedblood perfused neonatal heartpreparation Nomura et al

(2001) assessed the effects of

terminal warm blood cardioplegiaterminal warm oxygenated crys-talloid cardioplegia in comparisonwith conventional reperfusion(without any kind of terminal

cardioplegia) through assessmentrecovery of left ventricularfunction They demonstrated that

reperfusion with either terminalwarm blood cardioplegia or ter-

minal warm oxygenated crys-talloid cardioplegia resulted in

better recovery of myocardialfunction with slightly betterfunction in terminal warm bloodcardioplegia

In a clinically relevant intactanimal model that simulated theclinical condition of hypoxic

neonatal myocardium exposed toischemic stress Kronon et al

(2000) investigated the cardio-

protective effects of terminalwarm blood cardioplegic reper-fusion versus conventional reper-

fusion through assessment reco-

very of left ventricular systolicfunction and diastolic complianceThey showed that A warm cardio-

plegic reperfusion helps reduce

the reperfusion injury resultingin improved myocardial functionand metabolic recovery in hypoxicneonatal myocardium

Toyoda et al (2003) examined

the cardioprotective effect ofterminal warm blood cardioplegia inpediatric cardiac patients Blood

cardioplegia solution was composed

by mixing a hyperkalemic solutionwith oxygenated blood in 12dilutions with temperature 9oCThe terminal warm blood

cardioplegia had a finalconcentration of potassium 18mmolL-1 The results of Toyoda et alshowed beneficial effect of terminal

warm blood cardioplegia inreduction of myo-cardial injury Inagreement with Toyoda the

protocol of cardioplegiaadministered is almost similar asregard the concentration of pota-

ssium in terminal warm bloodcardioplegia (20mmolL-1) in 11

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Comparison of cardioprotective effects Hussein Sabri et al

26

dilution (1 crystalloid 1 blood) withsimilar result in myocardial pro-tection and improvement in aerobicenergy metabolism As a marker of

myocardial necrosis the currentstudy used troponin I whichprovides comparable information astroponin T used in the study ofToyoda

The current study is inagreement with Modi et al

(2004) who compared the use of

crystalloid cardioplegia cold blood

cardioplegia and cold blood

cardioplegia with hot-shot incyanotic and acyanotic pediatricpatients undergoing surgical

correction The efficacy of the 3

techniques was assessed byexamination right ventricularbiopsy specimen before and afterreperfusion analysis of cellular

metabolites and assessment oftroponin I level Their resultdemonstrated that for cyanotic

patients blood cardioplegia withhot-shot reduced metabolic injury

compared with cold crystalloidcardioplegia They also showed

that cold blood cardioplegia wason its own better than crystalloid

but not as good as cold bloodcardioplegia with hot-shot

Young et al (1997) failed to

demonstrate statistical advantage

for blood cardioplegia over crys-talloid cardioplegia in surgery forcongenital heart The most impor-

tant aspect of the study of Younget al is that no obvious benefitcan be anticipated by use of blood

cardioplegia in congenital heartsurgery when only antegrade

hypothermia dosing technique isused The integrated cardioplegicapproach using warm cold ante-grade and retrograde technique

with substrate enrichment may bebeneficial for pediatric population

As conclusion the result of

the current study showed that theuse of cardioplegia with hot-shot

provides the criteria that mayimprove myocardial protectionand reduce myocardial injury inpediatric population

These criteria include warm

blood accelerates recovery oftemperature-dependent enzymatic

and metabolic function highpotassium concentration prolongs

electromechanical arrest to decreaseenergy demands alkaloid solutionwhich counteracts tissue acidosisand high osmolarity which coun-teracts tissue edema

References

1 Allen BS Okamoto F

Buckberg GD Bugyi H

Young H Leaf J

Beyersdorf F Sjostrand F

and Maloney JV Jr

Studies of controlledreperfusion after ischemiaXV Immediate functional

recovery after six hours of

regional ischemia by careful

control of conditions ofreperfusion and compositionof reperfusate J Thorac

Cardiovasc Surg 1986 92(3Pt 2) 621-35

2 Allen BS Current Conceptsin Pediatric Myocardial

Protection In Salerno TA and

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

27

Ricci M (editors) MyocardialProtection 1st editionBlackwell publishing 2004207-29

3 Allen BS Pediatricmyocardial protection acardioplegic stra-tegy is the

solution Semin Thorac

Cardiovasc Surg Pediatr CardSurg Annu 2004 7 141-54

4 Bull C Cooper J and

Stark J Cardioplegicprotection of the childrsquos

heart J Thorac Cardio-vasc

Surg 1984 88(2) 287-93

5 Caputo M Dihmis WC

Bryan AJ Suleiman MS

and Angelini GD Warmblood hyperkalaemicreperfusion (hot shot)prevents myocardial substratederangement in patients

undergoing coronary arterybypass surgery Eur J

Cardiothorac Surg 199813(5) 559-64

6 Follette DM Fey K

Buckberg GD Helly JJ Jr

Steed DL Foglia RP and

Maloney JV Jr Reducingpostischemic damage by

temporary modifi-cation ofreperfusate calcium

potassium pH and

osmolarity J ThoracCardiovasc Surg 1981 82 (2)

221-38

7 Hammon JW Jr Myocardialprotection in the immatureheart Ann Thorac Surg 1995

60 (3) 839-842

8 Immer FF Stocker FP

Seiler AM Pfammatter JP

Printzen G and Carrel TP

Comparison of troponin-I and

troponin-T after pediatriccardiovascular opera-tion

Ann Thorac Surg 1998 66 (6)2073-7

9 Krause EG Pfeiffer D

Wollen-berger U and

Wollert HG Lactatemonitoring during and aftercardiopulmonary bypass an

approach implicating a peri-

operative measure for cardiacenergy metabolism In PiperHM Preusse CJ (editors)

Ischemia-reperfusion in

cardiac surgery 1st editionKluwer Academic 1993 317-33

10 Kronon MT Allen BS

Rahman S Wang T

Tayyab NA Bolling KS and

Ilbawi MN Reducingpostischemic reper-fusion

damage in neonates using a

terminal warm substrate-enriched blood cardioplegicreperfusate Ann Thorac Surg2000 70(3) 765-770

11 Modi P Suleiman MS

Reeves B Pawade A Parry

AJ Angelini GD and

Caputo M Myocardial

metabolic changes during ped-iatric cardiac surgery arando-mized study of 3cardioplegic techniques JThorac Cardiovasc Surg2004 128(1) 67-75

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

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Comparison of cardioprotective effects Hussein Sabri et al

28

12 Nomura F Forbess JM

and Mayer EJ Effects ofHot shot on recovery afterhypothermic ischemia in

neonatal lamb heart JCardiovasc Surg (Torino)2001 42(1) 1-7

13 Teoh KH Christakis GT

Weisel RD Fremes SE

Mickle DA Romaschin AD

Harding RS Ivanov J

Madonik MM Ross IM et

al Accelerated myocardial

metabolic recovery with

terminal warm bloodcardioplegia J ThoracCardiovasc Surg 1986 91(6)

888-95

14 Toyoda Y Yamaguchi M

Yoshimura N Oka S and

Okita Y Cardioprotectiveeffects and the mechanisms of

terminal warm bloodcardioplegia in pediatriccardiac surgery J ThoracCardiovasc Surg 2003 125

(6) 1242-51

15 Wernovsky G Wypij D

Jonas RA Mayer JE Jr

Hanley FL Hickey PR

Walsh AZ Chang AC

Castaneda AR NewburgerJW et al Postoperativecourse and hemodynamicprofile after the arterial

switch operation in neo-natesand infants A comparison of

low-flow cardiopulmonarybypass and circulatory arrestCirculation 1995 92(8) 2226-

35

16 Young JN Choy IO SilvaNK Obayashi DY and

Barkan HE Antegrade cold

blood cardioplegia is not

demonstrably advan-tageousover cold crystalloidcardioplegia in surgery forcongenital heart disease J

Thorac Cardiovasc Surg1997 114(6) 1002-9

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

17

O2 content CS oxygen content incoronary sinus blood sample

Myocardial lactate extraction

ratio was calculated according to

the following equation

Myocardial lactate extractionrate ratio= [lactate A - lactate CS] x100lactate A

Lactate A serum lactate concen-tration in arterial blood sample

Lactate CS serum lactate concen-

tration in coronary sinus bloodsample

Serum level of cardiac

troponin I (cTnI) Two millilitersof blood sample collected fromeach patient after induction of

anesthesia and at 4 8hrs afterdeclamping of the aorta Bloodsamples were centrifuged and

stored at -20deg until the completionof the study when thawed once

and assays were performed by a

laboratory technician blinded tothe clinical status of the patientor their inclusion in the studySerum concentration of cardiac

troponin I was determined with acommercially available enzyme-linked immunosorbent assay

(ELISA) kits cTnI ELISA-DRG

international Inc

Principle of the test Sample

was allowed to react with themicrotiter coated with monoclonalanti troponin I antibody (solid

phase) Monoclonal anti troponinI-enzyme (horseradish peroxidase)conjugate solution was added

resulting in the troponin I molec-

ules being sandwiched between

the solid phase and enzyme-linked antibodies

A solution of tetramethyl-benzidine (TMB) reagent was added

and incubated for 20 minutesresulting in the development of ablue color The color development

was stopped with the addition of 1Nhydrochloric acid (HCl) changing

the color to yellow The concen-tration of troponin I was directlyproportional to the color intensity ofthe test sample Absorbance was

measured spectrophotometrically

using Dade Behring Inc BEPreg

IIIat wavelength 450nm

Statistical analysis

All data were prospectively

collected coded tabulated thensubjected to statistical analysisusing SPSSreg for Windows version150 software packages Numericalvariables were presented as mean

and standard deviation (SD) while

categorical variables were presen-ted as number of cases and percent

Between-groups comparisons of

numerical variables were performedwith unpaired student-t test whilethose of categorical variables wereperformed by Fisher exact test orChi-square test as appropriate For

all tests P-value of less than 005

was considered statistically signifi-

cantResults

Patientsrsquo characteristics and

intraoperative data The demog-

raphic data and patients pathology

were comparable in both studygroups as shown in (Table 3)

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Comparison of cardioprotective effects Hussein Sabri et al

18

Intraoperative variables were alsocomparable in both study groups asshown in (Table 3) There was nosignificant difference as regards

cardiopulmonary bypass time (P

value was 0621) aortic cross-clamptime (P value was 0916) lowestoropharyngeal temperature (Pvalue was 0749)

Table 3 Patientsrsquo characteristics and intraoperative dataControl group

No =30

Hot-shot group

No =30P value

Age (month) 175 plusmn 56 181 plusmn 57 0716

Sex (MF) 1416 1614 0797

Weight (Kg) 141 plusmn 38 148 plusmn 42 0481

Pathology (n)

Acyanotic 17 19 ASD 6 7

VSD 7 9

CAVSD 4 3

Cyanotic 13 11

TOF 7 6

DORV- PS 6 5

CBP (min) 643plusmn 259 679plusmn 288 0621

Ao Cx (min) 378plusmn 169 382plusmn 171 0916

Oropharyngeal temp (degC) 306 plusmn 22 307 plusmn 20 0749

Mean plusmn SD MF male female ratio n number of patients ASD atrial septal defect

VSD ventricular septal defect CAVSD complete atrioventricular septal defect TOFtetralogy of Fallot DORV- PS double outlet right ventricle with pulmonary stenosis

CPB cardiopulmonary bypass Ao Cx aortic crossclamp P value is significant whenP lt 005 unpaired t test for age weight CBP Ao Cx and oropharyngeal temp

Fisherrsquos exact test for sex Chi-square test for pathology

Parameters of the study

Clinical outcome parameters

Intraoperative parametersThere was a significant difference

between both study groups after

declamping of the aorta Spon-taneous defibrillation into sinusrhythm occurred in 23 patients ofhot-shot group versus 10 patients of

control group (P value was 0002)Electrical defibrillation was requi-red in 7 patients of hotshot groupversus 20 patients of control group

(P value was 0002) (Table 4)

As regards requirement ofpacing to wean from cardio-pulmonary bypass there was no

significant difference between bothstudy groups Pacing was requiredin 5 patients of hot-shot groupversus 7 patients of control group (P

value was 0748) (Table 4)

As regards intraoperative

inotropes there was a significantdifference between both studygroups as regards number of

patients who required inotropes

for weaning of cardiopulmonarybypass Inotropes were requiredin 14 patients of hot-shot group

versus 24 patients of control group

(P value was 0015) (Table 4)

There was also a significantdifference between both groups as

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

19

regards inotropic score requiredfor weaning fromcardiopulmonary bypass Inotropescore was 44plusmn55 in hot-shot

group versus 105plusmn65 in controlgroup (P-value was lt0001)(Table 4)

Table 4 Intraoperative clinical outcome variablesControl

group

No =30

Hot-shot

group

No =30

P

value

Spontaneous defibrillation into sinusrhythm n ()

10 (333) 23 (767) 0002

Electrical defibrillation n () 20 (667) 7 (233) 0002

Requirement of pacing for weaning fromCBP n ()

7 (233) 5 (167) 0748

Requirement of intraoperative inotrope n

()24 (80) 14 (467) 0015

Inotrope score required for weaning from

CBP Mean plusmn SD 105plusmn

65 44plusmn

55 lt0001

n() Number (percentage) of patients Mean plusmnSD P-value is significant when Plt005 unpaired t

test for inotrope score P value is significant when P lt 005 Fisherrsquos exact test for spontaneous

defibrillation electrical defibrillation requirement of pacing and intraoperative inotrope

Postoperative parameters

There was a significant

difference between both studygroups as regards inotropes

required in the intensive careInotropes were required in 14

patients of hot-shot group versus24 patients of control group (Pvalue was 0015) Inotrope score

in the ICU was 754plusmn612 in hot-shot group versus 1225plusmn1032 incontrol group (P value was 0036)

Inotrope duration was 95plusmn72hrsin hot-shot group versus

149plusmn118hrs in control group (Pvalue was 0039) (Table 5)

As regards duration ofmechanical ventilation there was

no significant difference betweenboth study groups Duration ofmechanical ventilation was 67 plusmn 38

hrs in hot-shot group versus88plusmn44hrs in control group (Pvalue was 0053) (Table 5)

As regards duration of ICU

stay there was no significantdifference between both study

groups Duration of ICU stay was511plusmn188hrs in hot-shot groupversus 603plusmn231hrs in control

group (P-value was 0099) (Table

5)

There was no significantdifference between both study

groups as regards mortality Therewas no postoperative death in hot-shot group versus 3 postoperative

deaths in control group (P valuewas 0237) (Table 5)

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Comparison of cardioprotective effects Hussein Sabri et al

20

Table 5 Postoperative clinical outcome parametersControl

group

No =30

Hot-shot

group

No =30

P

value

Requirement of postoperative inotrope n () 24 (80) 14 (467) 0015

Inotrope score in ICU Meanplusmn SD 1225plusmn1032 754plusmn612 0036

Inotrope duration (h) Mean plusmn SD 149plusmn118 95plusmn72 0039

Duration of mechanical ventilation (h) Mean plusmn SD 88plusmn 44 67plusmn 38 0053

Duration of ICU stay (h) Mean plusmn SD 603 plusmn 231 511plusmn 188 0099

Mortality n () 3 (10) 0 (0) 0237

n () Number (percentage) of patients Mean plusmnSD P-value is significant when Plt005

unpaired t-test for inotrope score in ICU inotrope duration duration of mechanical Ventilation and duration of ICU stay P-value is significant when Plt005 Fisherrsquos exact test

for requirement of postoperative inotrope and mortality

Myocardial oxygen and lactate

extraction ratio As regards myo-

cardial oxygen extraction ratiothere was no significant differencebetween hot-shot group and

control group at the different

studied time intervals throughout

the initial sixty minutes ofreperfusion (P-value was gt005)(Table 6 Fig 1)

Table 6 Myocardial oxygen extraction ratio (MO2 ER)

Time interval after declamping of the aorta

Control

group

No =30

Hot-shot

group

No =30

P

value

M O2 ER immediately after declamping 529plusmn 62 512 plusmn 66 0308

M O2 ER 15 min after declamping 505plusmn 58 494 plusmn 61 0477

M O2 ER 30 min after declamping 492plusmn 55 480 plusmn 58 0414

M O2 ER 45 min after declamping 485plusmn 52 472 plusmn 55 0351

M O2 ER 60 min after declamping 476plusmn 51 468 plusmn 53 0554Mean plusmnSD P value is significant when P lt 005 unpaired t-test

983091983088

983091983093

983092983088

983092983093

983093983088

983093983093

983094983088

983088 983149983145983150 983089983093 983149983145983150 983091983088 983149983145983150 983092983093 983149983145983150 983094983088 983149983145983150

983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137

983117 983161 983151 983139 983137 983154 983140 983145 983137

983148 983151 983160 983161 983143 983141 983150 983141 983160 983156 983154 983137 983139 983156 983145 983151 983150 983154 983137 983156 983145 983151 983077 983139983151983150983156983154983151983148 983143983154983151983157983152

983144983151983156983085983155983144983151983156 983143983154983151983157983152

Fig 1 Myocardial oxygen extraction ratio Data are presented as mean Error bars represent

95 confidence interval

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

21

As regards myocardial lactateextraction ratio there was signi-ficant difference between hot-shotgroup and control group at the

different studied time intervals

throughout the initial sixtyminutes of reperfusion (P-valueswere 0027 0042 0024 lt0001lt0001 respectively) (Table 7

Fig 2)

Table 7 Myocardial lactate extraction ratio (M lactate ER)

Time interval after declamping of the aorta

Control

group

No =30

Hot-shot

group

No =30

P-

value

M lactate ER immediately after declamping -222plusmn 59 -190plusmn 50 0027

M lactate ER 15 min after declamping -136plusmn 50 -111plusmn 42 0042

M lactate ER 30 min after declamping -75plusmn 54 -44plusmn 49 0024

M lactate ER 45 min after declamping -48plusmn 40 00plusmn 46 lt0001

M lactate ER 60 min after declamping -26plusmn 34 59plusmn 41 lt0001

Mean plusmn SD P value is significant when Plt005 unpaired t-test

983085983091983088

983085983090983093

983085983090983088

983085983089983093

983085983089983088

983085983093

983088

983093

983089983088

983089983093

983090983088

983088 983149983145983150 983089983093 983149983145983150 983091983088 983149983145983150 983092983093 983149983145983150 983094983088 983149983145983150

983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137

983117 983161 983151 983139 983137 983154 983140 983145 983137 983148 983148 983137 983139 983156 983137 983156 983141 983141 983160 983156 983154 983137 983139 983156

983145 983151 983150 983154 983137 983156 983145 983151 983077

983139983151983150983156983154983151983148 983143983154983151983157983152

983144983151983156983085983155983144983151983156 983143983154983151983157983152

Fig 2 Myocardial lactate extraction ratio Data are presented as mean Error bars

represent 95 confidence interval P-value is significant when Plt005

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

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Comparison of cardioprotective effects Hussein Sabri et al

22

Serum level of cardiac troponinI (cTnI) There was no significantdifference between both studygroups as regards baseline values of

serum troponin I (P-value was0146) There was significantdifference between both study

groups in serum troponin I level at4 and 8 hours after declamping of

the aorta Serum troponin I level at

4 hours after declamping was132plusmn80ngml in hot-shot groupversus 313plusmn231ngml in controlgroup (P value was lt0001) Serum

troponin I level at 8 hours afterdeclamping was 100plusmn58ngml inhot-shot group versus 191plusmn115ngml in control group (P value waslt0001) (Table 8 Fig 3)

Table 8 Serum level of cardiac troponin I (cTnI)Control

group

No =30

Hot-shot

group

No =30

P

value

Baseline (ngml) 08plusmn

04 07plusmn

04 01464 hrs after declamping of the aorta (ngml) 313plusmn 231 132 plusmn 80 lt0001

8 hrs after declamping of the aorta (ngml) 191plusmn 115 100 plusmn 58 lt0001

Mean plusmn SD P-value is significant when P lt 005 unpaired t test

983088

983093

983089983088

983089983093

983090983088

983090983093

983091983088

983091983093

983092983088

983092983093

983138983137983155983141983148983145983150983141 983092 983144983154983155 983096 983144983154983155

983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137

983124 983154 983151 983152 983151 983150 983145 983150 983113 983080 983150 983143 983087 983149 983148 983081

983139983151983150983156983154983151983148 983143983154983151983157983152

983144983151983156983085983155983144983151983156 983143983154983151983157983152

Fig 3 Serum level of cardiac troponin I (cTnI) Data are presented as mean Errorbars represent 95 confidence interval P value is significant when P lt 005

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

23

Discussion

Low cardiac output aftersurgically induced ischemia andreperfusion continues to be a major

contributor to morbidity andmortality after pediatric cardiacsurgery and in more than 50 of

cases has been attributed toinadequate myocardial protection(Bull et al 1984 Hammon

1995)

Careful control of theconditions of reperfusion and the

composition of the reperfusate can

optimize postischemic recovery ofmyocardial function (Follette et

al 1981 Allen et al 1986)

The current study wasdesigned to evaluate the cardio-protective effect of using inter-mittent antegrade cold bloodcardioplegia versus intermittent

cold blood cardioplegia with ter-minal warm blood cardioplegia

(hot-shot) in pediatric cardiacpatients

The result of the current

study demonstrated significantdecrease in blood pressure at 5and 15 minutes interval in thecontrol group compared with the

hot-shot group after weaning ofthe cardiopulmonary bypass

Intermittent cold blood

cardioplegia with terminal warmblood cardioplegia offers favorable

effect on the clinical outcomeparameters This was demon-strated in this study as asignificant higher percentage ofspontaneous defibrillation into

sinus rhythm in hot-shot group

than control group (767 versus333 respectively)

The percentage of patientsrequiring inotropic support after

weaning from cardiopulmonarybypass was significantly higher incontrol group than hot-shot group

(80 versus 467 respectively)

By adopting the inotropic scoredescribed by Wernovsky et al

(1995) the level of inotropic

support was significantly lower inhot-shot group than control group

(44plusmn55 versus 105plusmn65 respec-

tively)

The improved clinical outcomerevealed the role of intermittent

cold blood cardioplegia withterminal warm blood cardioplegia inenhancement of myocardialprotection which was manifested asa reduction in myocardial arrhyth-

mia associated with ischemiareperfusion and a better myocardial

functionThe myocardial protective effect

of terminal warm blood cardioplegia

extended into the postoperativeperiod This was manifested as asignificant higher percentage ofpatients in control group than hot-

shot group who required inotropicsupport in the intensive care (80

versus 467 respectively) The

maximum dose of inotropic support(calculated by a modification of

inotropic score) was significantlyhigher in control group than hot-shot group (1225plusmn1032 versus754plusmn612 respectively) Theduration of inotropic support was

significantly higher in control group

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

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Comparison of cardioprotective effects Hussein Sabri et al

24

than hot-shot group (149plusmn118versus 95plusmn72 respectively)

In the postoperative periodresults were comparable as

regards duration of mechanicalventilation and stay in theintensive care unit in addition to

comparable mortality rate

Myocardial oxygen extraction

ratio reflects balance betweenmyocardial oxygen supply anddemand Myocardial oxygenextraction ratio was similar

between the two studied groups

This similarity may reflect theaerobic metabolic state of the

myocardium provided by the coldblood cardioplegia in both groups

Lactate release from theischemic myocytes is considered asa reflection of anaerobic metabolism(Krause et al 1993)

A negative myocardial lactateextraction ratio indicates that

amount of lactate productionthrough anaerobic glycolysis washigher than the amount of lactate

consumption for aerobic energy pro-duction with continuing anaerobicmetabolism and impairment ofnormal aerobic energy production

While a positive myocardial

lactate extraction ratio indicatesthat amount of lactate production

through anaerobic glycolysis wasless than the amount of lactate

consumption for aerobic energyproduction and that myocardiumstarts to use lactate as a substratevia oxidative phosphorylation

Myocardial lactate extractionratio in control group stayednegative value all through the sixtyminutes of studied period which

indicates impairment of aerobicmyocardial metabolism during thisperiod In hot-shot group myo-cardial lactate extraction ratioremained negative value till 45min

after declamping of the aorta when

it becomes a positive value

This point is considered a turnfrom anaerobic to aerobic meta-

bolism and it resembles the equilib-

rium between lactate consumptionand production At this point themyocardium starts to use lactate as

a substrate via oxidative phosphor-rylation (Krause et al 1993)

The results of this studydemonstrate the recovery of aerobicmetabolism afforded by inter-

mittent cold blood cardioplegia withterminal warm blood cardioplegiaTroponin I is a myocyte-contractileapparatus protein released follo-

wing myocardial damage Troponin

I Level is considered sensitivemarker of myocardial injuryassociated with cardiac surgery

(Immer et al 1998)

In this study we demonstrated

a significant increase in post-operative troponin I at 4 8 hoursafter declamping of the aorta in

control group compared to hot-shotgroup (P value was lt0001) Thisreflects the beneficial effect of warmcardioplegic reperfusion on myo-cardial outcome in reducing themyocardial damage following

ischemiareperfusion injury

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

25

In this study the composition ofterminal warm blood cardioplegiawas made to resemble the compo-sition of cold blood cardioplegia

used The point was to provide asolution with adequate potassiumconcentration to produce electro-mechanical arrest during reper-fusion This solution differs from the

conventional blood reperfusate in

presence of high potassiumconcentration (20mmolL-1) ahigher pH and a higher osmolarity

Thus cardioprotective effect ofterminal warm blood cardioplegia is

expected to be achieved byprolongation of electromechanicalarrest which reduces the energy

demands and counteracting tissueacidosis and edema therefore it

reduces the myocardial injury bypreservation and resynthesis ofhigh energy phosphates

There were small number ofclinical studies that have

examined specific myocardialprotection strategy in pediatric

population Utilizing an isolatedblood perfused neonatal heartpreparation Nomura et al

(2001) assessed the effects of

terminal warm blood cardioplegiaterminal warm oxygenated crys-talloid cardioplegia in comparisonwith conventional reperfusion(without any kind of terminal

cardioplegia) through assessmentrecovery of left ventricularfunction They demonstrated that

reperfusion with either terminalwarm blood cardioplegia or ter-

minal warm oxygenated crys-talloid cardioplegia resulted in

better recovery of myocardialfunction with slightly betterfunction in terminal warm bloodcardioplegia

In a clinically relevant intactanimal model that simulated theclinical condition of hypoxic

neonatal myocardium exposed toischemic stress Kronon et al

(2000) investigated the cardio-

protective effects of terminalwarm blood cardioplegic reper-fusion versus conventional reper-

fusion through assessment reco-

very of left ventricular systolicfunction and diastolic complianceThey showed that A warm cardio-

plegic reperfusion helps reduce

the reperfusion injury resultingin improved myocardial functionand metabolic recovery in hypoxicneonatal myocardium

Toyoda et al (2003) examined

the cardioprotective effect ofterminal warm blood cardioplegia inpediatric cardiac patients Blood

cardioplegia solution was composed

by mixing a hyperkalemic solutionwith oxygenated blood in 12dilutions with temperature 9oCThe terminal warm blood

cardioplegia had a finalconcentration of potassium 18mmolL-1 The results of Toyoda et alshowed beneficial effect of terminal

warm blood cardioplegia inreduction of myo-cardial injury Inagreement with Toyoda the

protocol of cardioplegiaadministered is almost similar asregard the concentration of pota-

ssium in terminal warm bloodcardioplegia (20mmolL-1) in 11

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

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Comparison of cardioprotective effects Hussein Sabri et al

26

dilution (1 crystalloid 1 blood) withsimilar result in myocardial pro-tection and improvement in aerobicenergy metabolism As a marker of

myocardial necrosis the currentstudy used troponin I whichprovides comparable information astroponin T used in the study ofToyoda

The current study is inagreement with Modi et al

(2004) who compared the use of

crystalloid cardioplegia cold blood

cardioplegia and cold blood

cardioplegia with hot-shot incyanotic and acyanotic pediatricpatients undergoing surgical

correction The efficacy of the 3

techniques was assessed byexamination right ventricularbiopsy specimen before and afterreperfusion analysis of cellular

metabolites and assessment oftroponin I level Their resultdemonstrated that for cyanotic

patients blood cardioplegia withhot-shot reduced metabolic injury

compared with cold crystalloidcardioplegia They also showed

that cold blood cardioplegia wason its own better than crystalloid

but not as good as cold bloodcardioplegia with hot-shot

Young et al (1997) failed to

demonstrate statistical advantage

for blood cardioplegia over crys-talloid cardioplegia in surgery forcongenital heart The most impor-

tant aspect of the study of Younget al is that no obvious benefitcan be anticipated by use of blood

cardioplegia in congenital heartsurgery when only antegrade

hypothermia dosing technique isused The integrated cardioplegicapproach using warm cold ante-grade and retrograde technique

with substrate enrichment may bebeneficial for pediatric population

As conclusion the result of

the current study showed that theuse of cardioplegia with hot-shot

provides the criteria that mayimprove myocardial protectionand reduce myocardial injury inpediatric population

These criteria include warm

blood accelerates recovery oftemperature-dependent enzymatic

and metabolic function highpotassium concentration prolongs

electromechanical arrest to decreaseenergy demands alkaloid solutionwhich counteracts tissue acidosisand high osmolarity which coun-teracts tissue edema

References

1 Allen BS Okamoto F

Buckberg GD Bugyi H

Young H Leaf J

Beyersdorf F Sjostrand F

and Maloney JV Jr

Studies of controlledreperfusion after ischemiaXV Immediate functional

recovery after six hours of

regional ischemia by careful

control of conditions ofreperfusion and compositionof reperfusate J Thorac

Cardiovasc Surg 1986 92(3Pt 2) 621-35

2 Allen BS Current Conceptsin Pediatric Myocardial

Protection In Salerno TA and

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

27

Ricci M (editors) MyocardialProtection 1st editionBlackwell publishing 2004207-29

3 Allen BS Pediatricmyocardial protection acardioplegic stra-tegy is the

solution Semin Thorac

Cardiovasc Surg Pediatr CardSurg Annu 2004 7 141-54

4 Bull C Cooper J and

Stark J Cardioplegicprotection of the childrsquos

heart J Thorac Cardio-vasc

Surg 1984 88(2) 287-93

5 Caputo M Dihmis WC

Bryan AJ Suleiman MS

and Angelini GD Warmblood hyperkalaemicreperfusion (hot shot)prevents myocardial substratederangement in patients

undergoing coronary arterybypass surgery Eur J

Cardiothorac Surg 199813(5) 559-64

6 Follette DM Fey K

Buckberg GD Helly JJ Jr

Steed DL Foglia RP and

Maloney JV Jr Reducingpostischemic damage by

temporary modifi-cation ofreperfusate calcium

potassium pH and

osmolarity J ThoracCardiovasc Surg 1981 82 (2)

221-38

7 Hammon JW Jr Myocardialprotection in the immatureheart Ann Thorac Surg 1995

60 (3) 839-842

8 Immer FF Stocker FP

Seiler AM Pfammatter JP

Printzen G and Carrel TP

Comparison of troponin-I and

troponin-T after pediatriccardiovascular opera-tion

Ann Thorac Surg 1998 66 (6)2073-7

9 Krause EG Pfeiffer D

Wollen-berger U and

Wollert HG Lactatemonitoring during and aftercardiopulmonary bypass an

approach implicating a peri-

operative measure for cardiacenergy metabolism In PiperHM Preusse CJ (editors)

Ischemia-reperfusion in

cardiac surgery 1st editionKluwer Academic 1993 317-33

10 Kronon MT Allen BS

Rahman S Wang T

Tayyab NA Bolling KS and

Ilbawi MN Reducingpostischemic reper-fusion

damage in neonates using a

terminal warm substrate-enriched blood cardioplegicreperfusate Ann Thorac Surg2000 70(3) 765-770

11 Modi P Suleiman MS

Reeves B Pawade A Parry

AJ Angelini GD and

Caputo M Myocardial

metabolic changes during ped-iatric cardiac surgery arando-mized study of 3cardioplegic techniques JThorac Cardiovasc Surg2004 128(1) 67-75

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

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Comparison of cardioprotective effects Hussein Sabri et al

28

12 Nomura F Forbess JM

and Mayer EJ Effects ofHot shot on recovery afterhypothermic ischemia in

neonatal lamb heart JCardiovasc Surg (Torino)2001 42(1) 1-7

13 Teoh KH Christakis GT

Weisel RD Fremes SE

Mickle DA Romaschin AD

Harding RS Ivanov J

Madonik MM Ross IM et

al Accelerated myocardial

metabolic recovery with

terminal warm bloodcardioplegia J ThoracCardiovasc Surg 1986 91(6)

888-95

14 Toyoda Y Yamaguchi M

Yoshimura N Oka S and

Okita Y Cardioprotectiveeffects and the mechanisms of

terminal warm bloodcardioplegia in pediatriccardiac surgery J ThoracCardiovasc Surg 2003 125

(6) 1242-51

15 Wernovsky G Wypij D

Jonas RA Mayer JE Jr

Hanley FL Hickey PR

Walsh AZ Chang AC

Castaneda AR NewburgerJW et al Postoperativecourse and hemodynamicprofile after the arterial

switch operation in neo-natesand infants A comparison of

low-flow cardiopulmonarybypass and circulatory arrestCirculation 1995 92(8) 2226-

35

16 Young JN Choy IO SilvaNK Obayashi DY and

Barkan HE Antegrade cold

blood cardioplegia is not

demonstrably advan-tageousover cold crystalloidcardioplegia in surgery forcongenital heart disease J

Thorac Cardiovasc Surg1997 114(6) 1002-9

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

17

O2 content CS oxygen content incoronary sinus blood sample

Myocardial lactate extraction

ratio was calculated according to

the following equation

Myocardial lactate extractionrate ratio= [lactate A - lactate CS] x100lactate A

Lactate A serum lactate concen-tration in arterial blood sample

Lactate CS serum lactate concen-

tration in coronary sinus bloodsample

Serum level of cardiac

troponin I (cTnI) Two millilitersof blood sample collected fromeach patient after induction of

anesthesia and at 4 8hrs afterdeclamping of the aorta Bloodsamples were centrifuged and

stored at -20deg until the completionof the study when thawed once

and assays were performed by a

laboratory technician blinded tothe clinical status of the patientor their inclusion in the studySerum concentration of cardiac

troponin I was determined with acommercially available enzyme-linked immunosorbent assay

(ELISA) kits cTnI ELISA-DRG

international Inc

Principle of the test Sample

was allowed to react with themicrotiter coated with monoclonalanti troponin I antibody (solid

phase) Monoclonal anti troponinI-enzyme (horseradish peroxidase)conjugate solution was added

resulting in the troponin I molec-

ules being sandwiched between

the solid phase and enzyme-linked antibodies

A solution of tetramethyl-benzidine (TMB) reagent was added

and incubated for 20 minutesresulting in the development of ablue color The color development

was stopped with the addition of 1Nhydrochloric acid (HCl) changing

the color to yellow The concen-tration of troponin I was directlyproportional to the color intensity ofthe test sample Absorbance was

measured spectrophotometrically

using Dade Behring Inc BEPreg

IIIat wavelength 450nm

Statistical analysis

All data were prospectively

collected coded tabulated thensubjected to statistical analysisusing SPSSreg for Windows version150 software packages Numericalvariables were presented as mean

and standard deviation (SD) while

categorical variables were presen-ted as number of cases and percent

Between-groups comparisons of

numerical variables were performedwith unpaired student-t test whilethose of categorical variables wereperformed by Fisher exact test orChi-square test as appropriate For

all tests P-value of less than 005

was considered statistically signifi-

cantResults

Patientsrsquo characteristics and

intraoperative data The demog-

raphic data and patients pathology

were comparable in both studygroups as shown in (Table 3)

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Comparison of cardioprotective effects Hussein Sabri et al

18

Intraoperative variables were alsocomparable in both study groups asshown in (Table 3) There was nosignificant difference as regards

cardiopulmonary bypass time (P

value was 0621) aortic cross-clamptime (P value was 0916) lowestoropharyngeal temperature (Pvalue was 0749)

Table 3 Patientsrsquo characteristics and intraoperative dataControl group

No =30

Hot-shot group

No =30P value

Age (month) 175 plusmn 56 181 plusmn 57 0716

Sex (MF) 1416 1614 0797

Weight (Kg) 141 plusmn 38 148 plusmn 42 0481

Pathology (n)

Acyanotic 17 19 ASD 6 7

VSD 7 9

CAVSD 4 3

Cyanotic 13 11

TOF 7 6

DORV- PS 6 5

CBP (min) 643plusmn 259 679plusmn 288 0621

Ao Cx (min) 378plusmn 169 382plusmn 171 0916

Oropharyngeal temp (degC) 306 plusmn 22 307 plusmn 20 0749

Mean plusmn SD MF male female ratio n number of patients ASD atrial septal defect

VSD ventricular septal defect CAVSD complete atrioventricular septal defect TOFtetralogy of Fallot DORV- PS double outlet right ventricle with pulmonary stenosis

CPB cardiopulmonary bypass Ao Cx aortic crossclamp P value is significant whenP lt 005 unpaired t test for age weight CBP Ao Cx and oropharyngeal temp

Fisherrsquos exact test for sex Chi-square test for pathology

Parameters of the study

Clinical outcome parameters

Intraoperative parametersThere was a significant difference

between both study groups after

declamping of the aorta Spon-taneous defibrillation into sinusrhythm occurred in 23 patients ofhot-shot group versus 10 patients of

control group (P value was 0002)Electrical defibrillation was requi-red in 7 patients of hotshot groupversus 20 patients of control group

(P value was 0002) (Table 4)

As regards requirement ofpacing to wean from cardio-pulmonary bypass there was no

significant difference between bothstudy groups Pacing was requiredin 5 patients of hot-shot groupversus 7 patients of control group (P

value was 0748) (Table 4)

As regards intraoperative

inotropes there was a significantdifference between both studygroups as regards number of

patients who required inotropes

for weaning of cardiopulmonarybypass Inotropes were requiredin 14 patients of hot-shot group

versus 24 patients of control group

(P value was 0015) (Table 4)

There was also a significantdifference between both groups as

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

19

regards inotropic score requiredfor weaning fromcardiopulmonary bypass Inotropescore was 44plusmn55 in hot-shot

group versus 105plusmn65 in controlgroup (P-value was lt0001)(Table 4)

Table 4 Intraoperative clinical outcome variablesControl

group

No =30

Hot-shot

group

No =30

P

value

Spontaneous defibrillation into sinusrhythm n ()

10 (333) 23 (767) 0002

Electrical defibrillation n () 20 (667) 7 (233) 0002

Requirement of pacing for weaning fromCBP n ()

7 (233) 5 (167) 0748

Requirement of intraoperative inotrope n

()24 (80) 14 (467) 0015

Inotrope score required for weaning from

CBP Mean plusmn SD 105plusmn

65 44plusmn

55 lt0001

n() Number (percentage) of patients Mean plusmnSD P-value is significant when Plt005 unpaired t

test for inotrope score P value is significant when P lt 005 Fisherrsquos exact test for spontaneous

defibrillation electrical defibrillation requirement of pacing and intraoperative inotrope

Postoperative parameters

There was a significant

difference between both studygroups as regards inotropes

required in the intensive careInotropes were required in 14

patients of hot-shot group versus24 patients of control group (Pvalue was 0015) Inotrope score

in the ICU was 754plusmn612 in hot-shot group versus 1225plusmn1032 incontrol group (P value was 0036)

Inotrope duration was 95plusmn72hrsin hot-shot group versus

149plusmn118hrs in control group (Pvalue was 0039) (Table 5)

As regards duration ofmechanical ventilation there was

no significant difference betweenboth study groups Duration ofmechanical ventilation was 67 plusmn 38

hrs in hot-shot group versus88plusmn44hrs in control group (Pvalue was 0053) (Table 5)

As regards duration of ICU

stay there was no significantdifference between both study

groups Duration of ICU stay was511plusmn188hrs in hot-shot groupversus 603plusmn231hrs in control

group (P-value was 0099) (Table

5)

There was no significantdifference between both study

groups as regards mortality Therewas no postoperative death in hot-shot group versus 3 postoperative

deaths in control group (P valuewas 0237) (Table 5)

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Comparison of cardioprotective effects Hussein Sabri et al

20

Table 5 Postoperative clinical outcome parametersControl

group

No =30

Hot-shot

group

No =30

P

value

Requirement of postoperative inotrope n () 24 (80) 14 (467) 0015

Inotrope score in ICU Meanplusmn SD 1225plusmn1032 754plusmn612 0036

Inotrope duration (h) Mean plusmn SD 149plusmn118 95plusmn72 0039

Duration of mechanical ventilation (h) Mean plusmn SD 88plusmn 44 67plusmn 38 0053

Duration of ICU stay (h) Mean plusmn SD 603 plusmn 231 511plusmn 188 0099

Mortality n () 3 (10) 0 (0) 0237

n () Number (percentage) of patients Mean plusmnSD P-value is significant when Plt005

unpaired t-test for inotrope score in ICU inotrope duration duration of mechanical Ventilation and duration of ICU stay P-value is significant when Plt005 Fisherrsquos exact test

for requirement of postoperative inotrope and mortality

Myocardial oxygen and lactate

extraction ratio As regards myo-

cardial oxygen extraction ratiothere was no significant differencebetween hot-shot group and

control group at the different

studied time intervals throughout

the initial sixty minutes ofreperfusion (P-value was gt005)(Table 6 Fig 1)

Table 6 Myocardial oxygen extraction ratio (MO2 ER)

Time interval after declamping of the aorta

Control

group

No =30

Hot-shot

group

No =30

P

value

M O2 ER immediately after declamping 529plusmn 62 512 plusmn 66 0308

M O2 ER 15 min after declamping 505plusmn 58 494 plusmn 61 0477

M O2 ER 30 min after declamping 492plusmn 55 480 plusmn 58 0414

M O2 ER 45 min after declamping 485plusmn 52 472 plusmn 55 0351

M O2 ER 60 min after declamping 476plusmn 51 468 plusmn 53 0554Mean plusmnSD P value is significant when P lt 005 unpaired t-test

983091983088

983091983093

983092983088

983092983093

983093983088

983093983093

983094983088

983088 983149983145983150 983089983093 983149983145983150 983091983088 983149983145983150 983092983093 983149983145983150 983094983088 983149983145983150

983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137

983117 983161 983151 983139 983137 983154 983140 983145 983137

983148 983151 983160 983161 983143 983141 983150 983141 983160 983156 983154 983137 983139 983156 983145 983151 983150 983154 983137 983156 983145 983151 983077 983139983151983150983156983154983151983148 983143983154983151983157983152

983144983151983156983085983155983144983151983156 983143983154983151983157983152

Fig 1 Myocardial oxygen extraction ratio Data are presented as mean Error bars represent

95 confidence interval

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

21

As regards myocardial lactateextraction ratio there was signi-ficant difference between hot-shotgroup and control group at the

different studied time intervals

throughout the initial sixtyminutes of reperfusion (P-valueswere 0027 0042 0024 lt0001lt0001 respectively) (Table 7

Fig 2)

Table 7 Myocardial lactate extraction ratio (M lactate ER)

Time interval after declamping of the aorta

Control

group

No =30

Hot-shot

group

No =30

P-

value

M lactate ER immediately after declamping -222plusmn 59 -190plusmn 50 0027

M lactate ER 15 min after declamping -136plusmn 50 -111plusmn 42 0042

M lactate ER 30 min after declamping -75plusmn 54 -44plusmn 49 0024

M lactate ER 45 min after declamping -48plusmn 40 00plusmn 46 lt0001

M lactate ER 60 min after declamping -26plusmn 34 59plusmn 41 lt0001

Mean plusmn SD P value is significant when Plt005 unpaired t-test

983085983091983088

983085983090983093

983085983090983088

983085983089983093

983085983089983088

983085983093

983088

983093

983089983088

983089983093

983090983088

983088 983149983145983150 983089983093 983149983145983150 983091983088 983149983145983150 983092983093 983149983145983150 983094983088 983149983145983150

983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137

983117 983161 983151 983139 983137 983154 983140 983145 983137 983148 983148 983137 983139 983156 983137 983156 983141 983141 983160 983156 983154 983137 983139 983156

983145 983151 983150 983154 983137 983156 983145 983151 983077

983139983151983150983156983154983151983148 983143983154983151983157983152

983144983151983156983085983155983144983151983156 983143983154983151983157983152

Fig 2 Myocardial lactate extraction ratio Data are presented as mean Error bars

represent 95 confidence interval P-value is significant when Plt005

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

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Comparison of cardioprotective effects Hussein Sabri et al

22

Serum level of cardiac troponinI (cTnI) There was no significantdifference between both studygroups as regards baseline values of

serum troponin I (P-value was0146) There was significantdifference between both study

groups in serum troponin I level at4 and 8 hours after declamping of

the aorta Serum troponin I level at

4 hours after declamping was132plusmn80ngml in hot-shot groupversus 313plusmn231ngml in controlgroup (P value was lt0001) Serum

troponin I level at 8 hours afterdeclamping was 100plusmn58ngml inhot-shot group versus 191plusmn115ngml in control group (P value waslt0001) (Table 8 Fig 3)

Table 8 Serum level of cardiac troponin I (cTnI)Control

group

No =30

Hot-shot

group

No =30

P

value

Baseline (ngml) 08plusmn

04 07plusmn

04 01464 hrs after declamping of the aorta (ngml) 313plusmn 231 132 plusmn 80 lt0001

8 hrs after declamping of the aorta (ngml) 191plusmn 115 100 plusmn 58 lt0001

Mean plusmn SD P-value is significant when P lt 005 unpaired t test

983088

983093

983089983088

983089983093

983090983088

983090983093

983091983088

983091983093

983092983088

983092983093

983138983137983155983141983148983145983150983141 983092 983144983154983155 983096 983144983154983155

983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137

983124 983154 983151 983152 983151 983150 983145 983150 983113 983080 983150 983143 983087 983149 983148 983081

983139983151983150983156983154983151983148 983143983154983151983157983152

983144983151983156983085983155983144983151983156 983143983154983151983157983152

Fig 3 Serum level of cardiac troponin I (cTnI) Data are presented as mean Errorbars represent 95 confidence interval P value is significant when P lt 005

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

23

Discussion

Low cardiac output aftersurgically induced ischemia andreperfusion continues to be a major

contributor to morbidity andmortality after pediatric cardiacsurgery and in more than 50 of

cases has been attributed toinadequate myocardial protection(Bull et al 1984 Hammon

1995)

Careful control of theconditions of reperfusion and the

composition of the reperfusate can

optimize postischemic recovery ofmyocardial function (Follette et

al 1981 Allen et al 1986)

The current study wasdesigned to evaluate the cardio-protective effect of using inter-mittent antegrade cold bloodcardioplegia versus intermittent

cold blood cardioplegia with ter-minal warm blood cardioplegia

(hot-shot) in pediatric cardiacpatients

The result of the current

study demonstrated significantdecrease in blood pressure at 5and 15 minutes interval in thecontrol group compared with the

hot-shot group after weaning ofthe cardiopulmonary bypass

Intermittent cold blood

cardioplegia with terminal warmblood cardioplegia offers favorable

effect on the clinical outcomeparameters This was demon-strated in this study as asignificant higher percentage ofspontaneous defibrillation into

sinus rhythm in hot-shot group

than control group (767 versus333 respectively)

The percentage of patientsrequiring inotropic support after

weaning from cardiopulmonarybypass was significantly higher incontrol group than hot-shot group

(80 versus 467 respectively)

By adopting the inotropic scoredescribed by Wernovsky et al

(1995) the level of inotropic

support was significantly lower inhot-shot group than control group

(44plusmn55 versus 105plusmn65 respec-

tively)

The improved clinical outcomerevealed the role of intermittent

cold blood cardioplegia withterminal warm blood cardioplegia inenhancement of myocardialprotection which was manifested asa reduction in myocardial arrhyth-

mia associated with ischemiareperfusion and a better myocardial

functionThe myocardial protective effect

of terminal warm blood cardioplegia

extended into the postoperativeperiod This was manifested as asignificant higher percentage ofpatients in control group than hot-

shot group who required inotropicsupport in the intensive care (80

versus 467 respectively) The

maximum dose of inotropic support(calculated by a modification of

inotropic score) was significantlyhigher in control group than hot-shot group (1225plusmn1032 versus754plusmn612 respectively) Theduration of inotropic support was

significantly higher in control group

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

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Comparison of cardioprotective effects Hussein Sabri et al

24

than hot-shot group (149plusmn118versus 95plusmn72 respectively)

In the postoperative periodresults were comparable as

regards duration of mechanicalventilation and stay in theintensive care unit in addition to

comparable mortality rate

Myocardial oxygen extraction

ratio reflects balance betweenmyocardial oxygen supply anddemand Myocardial oxygenextraction ratio was similar

between the two studied groups

This similarity may reflect theaerobic metabolic state of the

myocardium provided by the coldblood cardioplegia in both groups

Lactate release from theischemic myocytes is considered asa reflection of anaerobic metabolism(Krause et al 1993)

A negative myocardial lactateextraction ratio indicates that

amount of lactate productionthrough anaerobic glycolysis washigher than the amount of lactate

consumption for aerobic energy pro-duction with continuing anaerobicmetabolism and impairment ofnormal aerobic energy production

While a positive myocardial

lactate extraction ratio indicatesthat amount of lactate production

through anaerobic glycolysis wasless than the amount of lactate

consumption for aerobic energyproduction and that myocardiumstarts to use lactate as a substratevia oxidative phosphorylation

Myocardial lactate extractionratio in control group stayednegative value all through the sixtyminutes of studied period which

indicates impairment of aerobicmyocardial metabolism during thisperiod In hot-shot group myo-cardial lactate extraction ratioremained negative value till 45min

after declamping of the aorta when

it becomes a positive value

This point is considered a turnfrom anaerobic to aerobic meta-

bolism and it resembles the equilib-

rium between lactate consumptionand production At this point themyocardium starts to use lactate as

a substrate via oxidative phosphor-rylation (Krause et al 1993)

The results of this studydemonstrate the recovery of aerobicmetabolism afforded by inter-

mittent cold blood cardioplegia withterminal warm blood cardioplegiaTroponin I is a myocyte-contractileapparatus protein released follo-

wing myocardial damage Troponin

I Level is considered sensitivemarker of myocardial injuryassociated with cardiac surgery

(Immer et al 1998)

In this study we demonstrated

a significant increase in post-operative troponin I at 4 8 hoursafter declamping of the aorta in

control group compared to hot-shotgroup (P value was lt0001) Thisreflects the beneficial effect of warmcardioplegic reperfusion on myo-cardial outcome in reducing themyocardial damage following

ischemiareperfusion injury

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

25

In this study the composition ofterminal warm blood cardioplegiawas made to resemble the compo-sition of cold blood cardioplegia

used The point was to provide asolution with adequate potassiumconcentration to produce electro-mechanical arrest during reper-fusion This solution differs from the

conventional blood reperfusate in

presence of high potassiumconcentration (20mmolL-1) ahigher pH and a higher osmolarity

Thus cardioprotective effect ofterminal warm blood cardioplegia is

expected to be achieved byprolongation of electromechanicalarrest which reduces the energy

demands and counteracting tissueacidosis and edema therefore it

reduces the myocardial injury bypreservation and resynthesis ofhigh energy phosphates

There were small number ofclinical studies that have

examined specific myocardialprotection strategy in pediatric

population Utilizing an isolatedblood perfused neonatal heartpreparation Nomura et al

(2001) assessed the effects of

terminal warm blood cardioplegiaterminal warm oxygenated crys-talloid cardioplegia in comparisonwith conventional reperfusion(without any kind of terminal

cardioplegia) through assessmentrecovery of left ventricularfunction They demonstrated that

reperfusion with either terminalwarm blood cardioplegia or ter-

minal warm oxygenated crys-talloid cardioplegia resulted in

better recovery of myocardialfunction with slightly betterfunction in terminal warm bloodcardioplegia

In a clinically relevant intactanimal model that simulated theclinical condition of hypoxic

neonatal myocardium exposed toischemic stress Kronon et al

(2000) investigated the cardio-

protective effects of terminalwarm blood cardioplegic reper-fusion versus conventional reper-

fusion through assessment reco-

very of left ventricular systolicfunction and diastolic complianceThey showed that A warm cardio-

plegic reperfusion helps reduce

the reperfusion injury resultingin improved myocardial functionand metabolic recovery in hypoxicneonatal myocardium

Toyoda et al (2003) examined

the cardioprotective effect ofterminal warm blood cardioplegia inpediatric cardiac patients Blood

cardioplegia solution was composed

by mixing a hyperkalemic solutionwith oxygenated blood in 12dilutions with temperature 9oCThe terminal warm blood

cardioplegia had a finalconcentration of potassium 18mmolL-1 The results of Toyoda et alshowed beneficial effect of terminal

warm blood cardioplegia inreduction of myo-cardial injury Inagreement with Toyoda the

protocol of cardioplegiaadministered is almost similar asregard the concentration of pota-

ssium in terminal warm bloodcardioplegia (20mmolL-1) in 11

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Comparison of cardioprotective effects Hussein Sabri et al

26

dilution (1 crystalloid 1 blood) withsimilar result in myocardial pro-tection and improvement in aerobicenergy metabolism As a marker of

myocardial necrosis the currentstudy used troponin I whichprovides comparable information astroponin T used in the study ofToyoda

The current study is inagreement with Modi et al

(2004) who compared the use of

crystalloid cardioplegia cold blood

cardioplegia and cold blood

cardioplegia with hot-shot incyanotic and acyanotic pediatricpatients undergoing surgical

correction The efficacy of the 3

techniques was assessed byexamination right ventricularbiopsy specimen before and afterreperfusion analysis of cellular

metabolites and assessment oftroponin I level Their resultdemonstrated that for cyanotic

patients blood cardioplegia withhot-shot reduced metabolic injury

compared with cold crystalloidcardioplegia They also showed

that cold blood cardioplegia wason its own better than crystalloid

but not as good as cold bloodcardioplegia with hot-shot

Young et al (1997) failed to

demonstrate statistical advantage

for blood cardioplegia over crys-talloid cardioplegia in surgery forcongenital heart The most impor-

tant aspect of the study of Younget al is that no obvious benefitcan be anticipated by use of blood

cardioplegia in congenital heartsurgery when only antegrade

hypothermia dosing technique isused The integrated cardioplegicapproach using warm cold ante-grade and retrograde technique

with substrate enrichment may bebeneficial for pediatric population

As conclusion the result of

the current study showed that theuse of cardioplegia with hot-shot

provides the criteria that mayimprove myocardial protectionand reduce myocardial injury inpediatric population

These criteria include warm

blood accelerates recovery oftemperature-dependent enzymatic

and metabolic function highpotassium concentration prolongs

electromechanical arrest to decreaseenergy demands alkaloid solutionwhich counteracts tissue acidosisand high osmolarity which coun-teracts tissue edema

References

1 Allen BS Okamoto F

Buckberg GD Bugyi H

Young H Leaf J

Beyersdorf F Sjostrand F

and Maloney JV Jr

Studies of controlledreperfusion after ischemiaXV Immediate functional

recovery after six hours of

regional ischemia by careful

control of conditions ofreperfusion and compositionof reperfusate J Thorac

Cardiovasc Surg 1986 92(3Pt 2) 621-35

2 Allen BS Current Conceptsin Pediatric Myocardial

Protection In Salerno TA and

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

27

Ricci M (editors) MyocardialProtection 1st editionBlackwell publishing 2004207-29

3 Allen BS Pediatricmyocardial protection acardioplegic stra-tegy is the

solution Semin Thorac

Cardiovasc Surg Pediatr CardSurg Annu 2004 7 141-54

4 Bull C Cooper J and

Stark J Cardioplegicprotection of the childrsquos

heart J Thorac Cardio-vasc

Surg 1984 88(2) 287-93

5 Caputo M Dihmis WC

Bryan AJ Suleiman MS

and Angelini GD Warmblood hyperkalaemicreperfusion (hot shot)prevents myocardial substratederangement in patients

undergoing coronary arterybypass surgery Eur J

Cardiothorac Surg 199813(5) 559-64

6 Follette DM Fey K

Buckberg GD Helly JJ Jr

Steed DL Foglia RP and

Maloney JV Jr Reducingpostischemic damage by

temporary modifi-cation ofreperfusate calcium

potassium pH and

osmolarity J ThoracCardiovasc Surg 1981 82 (2)

221-38

7 Hammon JW Jr Myocardialprotection in the immatureheart Ann Thorac Surg 1995

60 (3) 839-842

8 Immer FF Stocker FP

Seiler AM Pfammatter JP

Printzen G and Carrel TP

Comparison of troponin-I and

troponin-T after pediatriccardiovascular opera-tion

Ann Thorac Surg 1998 66 (6)2073-7

9 Krause EG Pfeiffer D

Wollen-berger U and

Wollert HG Lactatemonitoring during and aftercardiopulmonary bypass an

approach implicating a peri-

operative measure for cardiacenergy metabolism In PiperHM Preusse CJ (editors)

Ischemia-reperfusion in

cardiac surgery 1st editionKluwer Academic 1993 317-33

10 Kronon MT Allen BS

Rahman S Wang T

Tayyab NA Bolling KS and

Ilbawi MN Reducingpostischemic reper-fusion

damage in neonates using a

terminal warm substrate-enriched blood cardioplegicreperfusate Ann Thorac Surg2000 70(3) 765-770

11 Modi P Suleiman MS

Reeves B Pawade A Parry

AJ Angelini GD and

Caputo M Myocardial

metabolic changes during ped-iatric cardiac surgery arando-mized study of 3cardioplegic techniques JThorac Cardiovasc Surg2004 128(1) 67-75

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

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Comparison of cardioprotective effects Hussein Sabri et al

28

12 Nomura F Forbess JM

and Mayer EJ Effects ofHot shot on recovery afterhypothermic ischemia in

neonatal lamb heart JCardiovasc Surg (Torino)2001 42(1) 1-7

13 Teoh KH Christakis GT

Weisel RD Fremes SE

Mickle DA Romaschin AD

Harding RS Ivanov J

Madonik MM Ross IM et

al Accelerated myocardial

metabolic recovery with

terminal warm bloodcardioplegia J ThoracCardiovasc Surg 1986 91(6)

888-95

14 Toyoda Y Yamaguchi M

Yoshimura N Oka S and

Okita Y Cardioprotectiveeffects and the mechanisms of

terminal warm bloodcardioplegia in pediatriccardiac surgery J ThoracCardiovasc Surg 2003 125

(6) 1242-51

15 Wernovsky G Wypij D

Jonas RA Mayer JE Jr

Hanley FL Hickey PR

Walsh AZ Chang AC

Castaneda AR NewburgerJW et al Postoperativecourse and hemodynamicprofile after the arterial

switch operation in neo-natesand infants A comparison of

low-flow cardiopulmonarybypass and circulatory arrestCirculation 1995 92(8) 2226-

35

16 Young JN Choy IO SilvaNK Obayashi DY and

Barkan HE Antegrade cold

blood cardioplegia is not

demonstrably advan-tageousover cold crystalloidcardioplegia in surgery forcongenital heart disease J

Thorac Cardiovasc Surg1997 114(6) 1002-9

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Comparison of cardioprotective effects Hussein Sabri et al

18

Intraoperative variables were alsocomparable in both study groups asshown in (Table 3) There was nosignificant difference as regards

cardiopulmonary bypass time (P

value was 0621) aortic cross-clamptime (P value was 0916) lowestoropharyngeal temperature (Pvalue was 0749)

Table 3 Patientsrsquo characteristics and intraoperative dataControl group

No =30

Hot-shot group

No =30P value

Age (month) 175 plusmn 56 181 plusmn 57 0716

Sex (MF) 1416 1614 0797

Weight (Kg) 141 plusmn 38 148 plusmn 42 0481

Pathology (n)

Acyanotic 17 19 ASD 6 7

VSD 7 9

CAVSD 4 3

Cyanotic 13 11

TOF 7 6

DORV- PS 6 5

CBP (min) 643plusmn 259 679plusmn 288 0621

Ao Cx (min) 378plusmn 169 382plusmn 171 0916

Oropharyngeal temp (degC) 306 plusmn 22 307 plusmn 20 0749

Mean plusmn SD MF male female ratio n number of patients ASD atrial septal defect

VSD ventricular septal defect CAVSD complete atrioventricular septal defect TOFtetralogy of Fallot DORV- PS double outlet right ventricle with pulmonary stenosis

CPB cardiopulmonary bypass Ao Cx aortic crossclamp P value is significant whenP lt 005 unpaired t test for age weight CBP Ao Cx and oropharyngeal temp

Fisherrsquos exact test for sex Chi-square test for pathology

Parameters of the study

Clinical outcome parameters

Intraoperative parametersThere was a significant difference

between both study groups after

declamping of the aorta Spon-taneous defibrillation into sinusrhythm occurred in 23 patients ofhot-shot group versus 10 patients of

control group (P value was 0002)Electrical defibrillation was requi-red in 7 patients of hotshot groupversus 20 patients of control group

(P value was 0002) (Table 4)

As regards requirement ofpacing to wean from cardio-pulmonary bypass there was no

significant difference between bothstudy groups Pacing was requiredin 5 patients of hot-shot groupversus 7 patients of control group (P

value was 0748) (Table 4)

As regards intraoperative

inotropes there was a significantdifference between both studygroups as regards number of

patients who required inotropes

for weaning of cardiopulmonarybypass Inotropes were requiredin 14 patients of hot-shot group

versus 24 patients of control group

(P value was 0015) (Table 4)

There was also a significantdifference between both groups as

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

19

regards inotropic score requiredfor weaning fromcardiopulmonary bypass Inotropescore was 44plusmn55 in hot-shot

group versus 105plusmn65 in controlgroup (P-value was lt0001)(Table 4)

Table 4 Intraoperative clinical outcome variablesControl

group

No =30

Hot-shot

group

No =30

P

value

Spontaneous defibrillation into sinusrhythm n ()

10 (333) 23 (767) 0002

Electrical defibrillation n () 20 (667) 7 (233) 0002

Requirement of pacing for weaning fromCBP n ()

7 (233) 5 (167) 0748

Requirement of intraoperative inotrope n

()24 (80) 14 (467) 0015

Inotrope score required for weaning from

CBP Mean plusmn SD 105plusmn

65 44plusmn

55 lt0001

n() Number (percentage) of patients Mean plusmnSD P-value is significant when Plt005 unpaired t

test for inotrope score P value is significant when P lt 005 Fisherrsquos exact test for spontaneous

defibrillation electrical defibrillation requirement of pacing and intraoperative inotrope

Postoperative parameters

There was a significant

difference between both studygroups as regards inotropes

required in the intensive careInotropes were required in 14

patients of hot-shot group versus24 patients of control group (Pvalue was 0015) Inotrope score

in the ICU was 754plusmn612 in hot-shot group versus 1225plusmn1032 incontrol group (P value was 0036)

Inotrope duration was 95plusmn72hrsin hot-shot group versus

149plusmn118hrs in control group (Pvalue was 0039) (Table 5)

As regards duration ofmechanical ventilation there was

no significant difference betweenboth study groups Duration ofmechanical ventilation was 67 plusmn 38

hrs in hot-shot group versus88plusmn44hrs in control group (Pvalue was 0053) (Table 5)

As regards duration of ICU

stay there was no significantdifference between both study

groups Duration of ICU stay was511plusmn188hrs in hot-shot groupversus 603plusmn231hrs in control

group (P-value was 0099) (Table

5)

There was no significantdifference between both study

groups as regards mortality Therewas no postoperative death in hot-shot group versus 3 postoperative

deaths in control group (P valuewas 0237) (Table 5)

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

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Comparison of cardioprotective effects Hussein Sabri et al

20

Table 5 Postoperative clinical outcome parametersControl

group

No =30

Hot-shot

group

No =30

P

value

Requirement of postoperative inotrope n () 24 (80) 14 (467) 0015

Inotrope score in ICU Meanplusmn SD 1225plusmn1032 754plusmn612 0036

Inotrope duration (h) Mean plusmn SD 149plusmn118 95plusmn72 0039

Duration of mechanical ventilation (h) Mean plusmn SD 88plusmn 44 67plusmn 38 0053

Duration of ICU stay (h) Mean plusmn SD 603 plusmn 231 511plusmn 188 0099

Mortality n () 3 (10) 0 (0) 0237

n () Number (percentage) of patients Mean plusmnSD P-value is significant when Plt005

unpaired t-test for inotrope score in ICU inotrope duration duration of mechanical Ventilation and duration of ICU stay P-value is significant when Plt005 Fisherrsquos exact test

for requirement of postoperative inotrope and mortality

Myocardial oxygen and lactate

extraction ratio As regards myo-

cardial oxygen extraction ratiothere was no significant differencebetween hot-shot group and

control group at the different

studied time intervals throughout

the initial sixty minutes ofreperfusion (P-value was gt005)(Table 6 Fig 1)

Table 6 Myocardial oxygen extraction ratio (MO2 ER)

Time interval after declamping of the aorta

Control

group

No =30

Hot-shot

group

No =30

P

value

M O2 ER immediately after declamping 529plusmn 62 512 plusmn 66 0308

M O2 ER 15 min after declamping 505plusmn 58 494 plusmn 61 0477

M O2 ER 30 min after declamping 492plusmn 55 480 plusmn 58 0414

M O2 ER 45 min after declamping 485plusmn 52 472 plusmn 55 0351

M O2 ER 60 min after declamping 476plusmn 51 468 plusmn 53 0554Mean plusmnSD P value is significant when P lt 005 unpaired t-test

983091983088

983091983093

983092983088

983092983093

983093983088

983093983093

983094983088

983088 983149983145983150 983089983093 983149983145983150 983091983088 983149983145983150 983092983093 983149983145983150 983094983088 983149983145983150

983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137

983117 983161 983151 983139 983137 983154 983140 983145 983137

983148 983151 983160 983161 983143 983141 983150 983141 983160 983156 983154 983137 983139 983156 983145 983151 983150 983154 983137 983156 983145 983151 983077 983139983151983150983156983154983151983148 983143983154983151983157983152

983144983151983156983085983155983144983151983156 983143983154983151983157983152

Fig 1 Myocardial oxygen extraction ratio Data are presented as mean Error bars represent

95 confidence interval

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

21

As regards myocardial lactateextraction ratio there was signi-ficant difference between hot-shotgroup and control group at the

different studied time intervals

throughout the initial sixtyminutes of reperfusion (P-valueswere 0027 0042 0024 lt0001lt0001 respectively) (Table 7

Fig 2)

Table 7 Myocardial lactate extraction ratio (M lactate ER)

Time interval after declamping of the aorta

Control

group

No =30

Hot-shot

group

No =30

P-

value

M lactate ER immediately after declamping -222plusmn 59 -190plusmn 50 0027

M lactate ER 15 min after declamping -136plusmn 50 -111plusmn 42 0042

M lactate ER 30 min after declamping -75plusmn 54 -44plusmn 49 0024

M lactate ER 45 min after declamping -48plusmn 40 00plusmn 46 lt0001

M lactate ER 60 min after declamping -26plusmn 34 59plusmn 41 lt0001

Mean plusmn SD P value is significant when Plt005 unpaired t-test

983085983091983088

983085983090983093

983085983090983088

983085983089983093

983085983089983088

983085983093

983088

983093

983089983088

983089983093

983090983088

983088 983149983145983150 983089983093 983149983145983150 983091983088 983149983145983150 983092983093 983149983145983150 983094983088 983149983145983150

983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137

983117 983161 983151 983139 983137 983154 983140 983145 983137 983148 983148 983137 983139 983156 983137 983156 983141 983141 983160 983156 983154 983137 983139 983156

983145 983151 983150 983154 983137 983156 983145 983151 983077

983139983151983150983156983154983151983148 983143983154983151983157983152

983144983151983156983085983155983144983151983156 983143983154983151983157983152

Fig 2 Myocardial lactate extraction ratio Data are presented as mean Error bars

represent 95 confidence interval P-value is significant when Plt005

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

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Comparison of cardioprotective effects Hussein Sabri et al

22

Serum level of cardiac troponinI (cTnI) There was no significantdifference between both studygroups as regards baseline values of

serum troponin I (P-value was0146) There was significantdifference between both study

groups in serum troponin I level at4 and 8 hours after declamping of

the aorta Serum troponin I level at

4 hours after declamping was132plusmn80ngml in hot-shot groupversus 313plusmn231ngml in controlgroup (P value was lt0001) Serum

troponin I level at 8 hours afterdeclamping was 100plusmn58ngml inhot-shot group versus 191plusmn115ngml in control group (P value waslt0001) (Table 8 Fig 3)

Table 8 Serum level of cardiac troponin I (cTnI)Control

group

No =30

Hot-shot

group

No =30

P

value

Baseline (ngml) 08plusmn

04 07plusmn

04 01464 hrs after declamping of the aorta (ngml) 313plusmn 231 132 plusmn 80 lt0001

8 hrs after declamping of the aorta (ngml) 191plusmn 115 100 plusmn 58 lt0001

Mean plusmn SD P-value is significant when P lt 005 unpaired t test

983088

983093

983089983088

983089983093

983090983088

983090983093

983091983088

983091983093

983092983088

983092983093

983138983137983155983141983148983145983150983141 983092 983144983154983155 983096 983144983154983155

983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137

983124 983154 983151 983152 983151 983150 983145 983150 983113 983080 983150 983143 983087 983149 983148 983081

983139983151983150983156983154983151983148 983143983154983151983157983152

983144983151983156983085983155983144983151983156 983143983154983151983157983152

Fig 3 Serum level of cardiac troponin I (cTnI) Data are presented as mean Errorbars represent 95 confidence interval P value is significant when P lt 005

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

23

Discussion

Low cardiac output aftersurgically induced ischemia andreperfusion continues to be a major

contributor to morbidity andmortality after pediatric cardiacsurgery and in more than 50 of

cases has been attributed toinadequate myocardial protection(Bull et al 1984 Hammon

1995)

Careful control of theconditions of reperfusion and the

composition of the reperfusate can

optimize postischemic recovery ofmyocardial function (Follette et

al 1981 Allen et al 1986)

The current study wasdesigned to evaluate the cardio-protective effect of using inter-mittent antegrade cold bloodcardioplegia versus intermittent

cold blood cardioplegia with ter-minal warm blood cardioplegia

(hot-shot) in pediatric cardiacpatients

The result of the current

study demonstrated significantdecrease in blood pressure at 5and 15 minutes interval in thecontrol group compared with the

hot-shot group after weaning ofthe cardiopulmonary bypass

Intermittent cold blood

cardioplegia with terminal warmblood cardioplegia offers favorable

effect on the clinical outcomeparameters This was demon-strated in this study as asignificant higher percentage ofspontaneous defibrillation into

sinus rhythm in hot-shot group

than control group (767 versus333 respectively)

The percentage of patientsrequiring inotropic support after

weaning from cardiopulmonarybypass was significantly higher incontrol group than hot-shot group

(80 versus 467 respectively)

By adopting the inotropic scoredescribed by Wernovsky et al

(1995) the level of inotropic

support was significantly lower inhot-shot group than control group

(44plusmn55 versus 105plusmn65 respec-

tively)

The improved clinical outcomerevealed the role of intermittent

cold blood cardioplegia withterminal warm blood cardioplegia inenhancement of myocardialprotection which was manifested asa reduction in myocardial arrhyth-

mia associated with ischemiareperfusion and a better myocardial

functionThe myocardial protective effect

of terminal warm blood cardioplegia

extended into the postoperativeperiod This was manifested as asignificant higher percentage ofpatients in control group than hot-

shot group who required inotropicsupport in the intensive care (80

versus 467 respectively) The

maximum dose of inotropic support(calculated by a modification of

inotropic score) was significantlyhigher in control group than hot-shot group (1225plusmn1032 versus754plusmn612 respectively) Theduration of inotropic support was

significantly higher in control group

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

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Comparison of cardioprotective effects Hussein Sabri et al

24

than hot-shot group (149plusmn118versus 95plusmn72 respectively)

In the postoperative periodresults were comparable as

regards duration of mechanicalventilation and stay in theintensive care unit in addition to

comparable mortality rate

Myocardial oxygen extraction

ratio reflects balance betweenmyocardial oxygen supply anddemand Myocardial oxygenextraction ratio was similar

between the two studied groups

This similarity may reflect theaerobic metabolic state of the

myocardium provided by the coldblood cardioplegia in both groups

Lactate release from theischemic myocytes is considered asa reflection of anaerobic metabolism(Krause et al 1993)

A negative myocardial lactateextraction ratio indicates that

amount of lactate productionthrough anaerobic glycolysis washigher than the amount of lactate

consumption for aerobic energy pro-duction with continuing anaerobicmetabolism and impairment ofnormal aerobic energy production

While a positive myocardial

lactate extraction ratio indicatesthat amount of lactate production

through anaerobic glycolysis wasless than the amount of lactate

consumption for aerobic energyproduction and that myocardiumstarts to use lactate as a substratevia oxidative phosphorylation

Myocardial lactate extractionratio in control group stayednegative value all through the sixtyminutes of studied period which

indicates impairment of aerobicmyocardial metabolism during thisperiod In hot-shot group myo-cardial lactate extraction ratioremained negative value till 45min

after declamping of the aorta when

it becomes a positive value

This point is considered a turnfrom anaerobic to aerobic meta-

bolism and it resembles the equilib-

rium between lactate consumptionand production At this point themyocardium starts to use lactate as

a substrate via oxidative phosphor-rylation (Krause et al 1993)

The results of this studydemonstrate the recovery of aerobicmetabolism afforded by inter-

mittent cold blood cardioplegia withterminal warm blood cardioplegiaTroponin I is a myocyte-contractileapparatus protein released follo-

wing myocardial damage Troponin

I Level is considered sensitivemarker of myocardial injuryassociated with cardiac surgery

(Immer et al 1998)

In this study we demonstrated

a significant increase in post-operative troponin I at 4 8 hoursafter declamping of the aorta in

control group compared to hot-shotgroup (P value was lt0001) Thisreflects the beneficial effect of warmcardioplegic reperfusion on myo-cardial outcome in reducing themyocardial damage following

ischemiareperfusion injury

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

25

In this study the composition ofterminal warm blood cardioplegiawas made to resemble the compo-sition of cold blood cardioplegia

used The point was to provide asolution with adequate potassiumconcentration to produce electro-mechanical arrest during reper-fusion This solution differs from the

conventional blood reperfusate in

presence of high potassiumconcentration (20mmolL-1) ahigher pH and a higher osmolarity

Thus cardioprotective effect ofterminal warm blood cardioplegia is

expected to be achieved byprolongation of electromechanicalarrest which reduces the energy

demands and counteracting tissueacidosis and edema therefore it

reduces the myocardial injury bypreservation and resynthesis ofhigh energy phosphates

There were small number ofclinical studies that have

examined specific myocardialprotection strategy in pediatric

population Utilizing an isolatedblood perfused neonatal heartpreparation Nomura et al

(2001) assessed the effects of

terminal warm blood cardioplegiaterminal warm oxygenated crys-talloid cardioplegia in comparisonwith conventional reperfusion(without any kind of terminal

cardioplegia) through assessmentrecovery of left ventricularfunction They demonstrated that

reperfusion with either terminalwarm blood cardioplegia or ter-

minal warm oxygenated crys-talloid cardioplegia resulted in

better recovery of myocardialfunction with slightly betterfunction in terminal warm bloodcardioplegia

In a clinically relevant intactanimal model that simulated theclinical condition of hypoxic

neonatal myocardium exposed toischemic stress Kronon et al

(2000) investigated the cardio-

protective effects of terminalwarm blood cardioplegic reper-fusion versus conventional reper-

fusion through assessment reco-

very of left ventricular systolicfunction and diastolic complianceThey showed that A warm cardio-

plegic reperfusion helps reduce

the reperfusion injury resultingin improved myocardial functionand metabolic recovery in hypoxicneonatal myocardium

Toyoda et al (2003) examined

the cardioprotective effect ofterminal warm blood cardioplegia inpediatric cardiac patients Blood

cardioplegia solution was composed

by mixing a hyperkalemic solutionwith oxygenated blood in 12dilutions with temperature 9oCThe terminal warm blood

cardioplegia had a finalconcentration of potassium 18mmolL-1 The results of Toyoda et alshowed beneficial effect of terminal

warm blood cardioplegia inreduction of myo-cardial injury Inagreement with Toyoda the

protocol of cardioplegiaadministered is almost similar asregard the concentration of pota-

ssium in terminal warm bloodcardioplegia (20mmolL-1) in 11

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Comparison of cardioprotective effects Hussein Sabri et al

26

dilution (1 crystalloid 1 blood) withsimilar result in myocardial pro-tection and improvement in aerobicenergy metabolism As a marker of

myocardial necrosis the currentstudy used troponin I whichprovides comparable information astroponin T used in the study ofToyoda

The current study is inagreement with Modi et al

(2004) who compared the use of

crystalloid cardioplegia cold blood

cardioplegia and cold blood

cardioplegia with hot-shot incyanotic and acyanotic pediatricpatients undergoing surgical

correction The efficacy of the 3

techniques was assessed byexamination right ventricularbiopsy specimen before and afterreperfusion analysis of cellular

metabolites and assessment oftroponin I level Their resultdemonstrated that for cyanotic

patients blood cardioplegia withhot-shot reduced metabolic injury

compared with cold crystalloidcardioplegia They also showed

that cold blood cardioplegia wason its own better than crystalloid

but not as good as cold bloodcardioplegia with hot-shot

Young et al (1997) failed to

demonstrate statistical advantage

for blood cardioplegia over crys-talloid cardioplegia in surgery forcongenital heart The most impor-

tant aspect of the study of Younget al is that no obvious benefitcan be anticipated by use of blood

cardioplegia in congenital heartsurgery when only antegrade

hypothermia dosing technique isused The integrated cardioplegicapproach using warm cold ante-grade and retrograde technique

with substrate enrichment may bebeneficial for pediatric population

As conclusion the result of

the current study showed that theuse of cardioplegia with hot-shot

provides the criteria that mayimprove myocardial protectionand reduce myocardial injury inpediatric population

These criteria include warm

blood accelerates recovery oftemperature-dependent enzymatic

and metabolic function highpotassium concentration prolongs

electromechanical arrest to decreaseenergy demands alkaloid solutionwhich counteracts tissue acidosisand high osmolarity which coun-teracts tissue edema

References

1 Allen BS Okamoto F

Buckberg GD Bugyi H

Young H Leaf J

Beyersdorf F Sjostrand F

and Maloney JV Jr

Studies of controlledreperfusion after ischemiaXV Immediate functional

recovery after six hours of

regional ischemia by careful

control of conditions ofreperfusion and compositionof reperfusate J Thorac

Cardiovasc Surg 1986 92(3Pt 2) 621-35

2 Allen BS Current Conceptsin Pediatric Myocardial

Protection In Salerno TA and

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

27

Ricci M (editors) MyocardialProtection 1st editionBlackwell publishing 2004207-29

3 Allen BS Pediatricmyocardial protection acardioplegic stra-tegy is the

solution Semin Thorac

Cardiovasc Surg Pediatr CardSurg Annu 2004 7 141-54

4 Bull C Cooper J and

Stark J Cardioplegicprotection of the childrsquos

heart J Thorac Cardio-vasc

Surg 1984 88(2) 287-93

5 Caputo M Dihmis WC

Bryan AJ Suleiman MS

and Angelini GD Warmblood hyperkalaemicreperfusion (hot shot)prevents myocardial substratederangement in patients

undergoing coronary arterybypass surgery Eur J

Cardiothorac Surg 199813(5) 559-64

6 Follette DM Fey K

Buckberg GD Helly JJ Jr

Steed DL Foglia RP and

Maloney JV Jr Reducingpostischemic damage by

temporary modifi-cation ofreperfusate calcium

potassium pH and

osmolarity J ThoracCardiovasc Surg 1981 82 (2)

221-38

7 Hammon JW Jr Myocardialprotection in the immatureheart Ann Thorac Surg 1995

60 (3) 839-842

8 Immer FF Stocker FP

Seiler AM Pfammatter JP

Printzen G and Carrel TP

Comparison of troponin-I and

troponin-T after pediatriccardiovascular opera-tion

Ann Thorac Surg 1998 66 (6)2073-7

9 Krause EG Pfeiffer D

Wollen-berger U and

Wollert HG Lactatemonitoring during and aftercardiopulmonary bypass an

approach implicating a peri-

operative measure for cardiacenergy metabolism In PiperHM Preusse CJ (editors)

Ischemia-reperfusion in

cardiac surgery 1st editionKluwer Academic 1993 317-33

10 Kronon MT Allen BS

Rahman S Wang T

Tayyab NA Bolling KS and

Ilbawi MN Reducingpostischemic reper-fusion

damage in neonates using a

terminal warm substrate-enriched blood cardioplegicreperfusate Ann Thorac Surg2000 70(3) 765-770

11 Modi P Suleiman MS

Reeves B Pawade A Parry

AJ Angelini GD and

Caputo M Myocardial

metabolic changes during ped-iatric cardiac surgery arando-mized study of 3cardioplegic techniques JThorac Cardiovasc Surg2004 128(1) 67-75

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

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Comparison of cardioprotective effects Hussein Sabri et al

28

12 Nomura F Forbess JM

and Mayer EJ Effects ofHot shot on recovery afterhypothermic ischemia in

neonatal lamb heart JCardiovasc Surg (Torino)2001 42(1) 1-7

13 Teoh KH Christakis GT

Weisel RD Fremes SE

Mickle DA Romaschin AD

Harding RS Ivanov J

Madonik MM Ross IM et

al Accelerated myocardial

metabolic recovery with

terminal warm bloodcardioplegia J ThoracCardiovasc Surg 1986 91(6)

888-95

14 Toyoda Y Yamaguchi M

Yoshimura N Oka S and

Okita Y Cardioprotectiveeffects and the mechanisms of

terminal warm bloodcardioplegia in pediatriccardiac surgery J ThoracCardiovasc Surg 2003 125

(6) 1242-51

15 Wernovsky G Wypij D

Jonas RA Mayer JE Jr

Hanley FL Hickey PR

Walsh AZ Chang AC

Castaneda AR NewburgerJW et al Postoperativecourse and hemodynamicprofile after the arterial

switch operation in neo-natesand infants A comparison of

low-flow cardiopulmonarybypass and circulatory arrestCirculation 1995 92(8) 2226-

35

16 Young JN Choy IO SilvaNK Obayashi DY and

Barkan HE Antegrade cold

blood cardioplegia is not

demonstrably advan-tageousover cold crystalloidcardioplegia in surgery forcongenital heart disease J

Thorac Cardiovasc Surg1997 114(6) 1002-9

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

19

regards inotropic score requiredfor weaning fromcardiopulmonary bypass Inotropescore was 44plusmn55 in hot-shot

group versus 105plusmn65 in controlgroup (P-value was lt0001)(Table 4)

Table 4 Intraoperative clinical outcome variablesControl

group

No =30

Hot-shot

group

No =30

P

value

Spontaneous defibrillation into sinusrhythm n ()

10 (333) 23 (767) 0002

Electrical defibrillation n () 20 (667) 7 (233) 0002

Requirement of pacing for weaning fromCBP n ()

7 (233) 5 (167) 0748

Requirement of intraoperative inotrope n

()24 (80) 14 (467) 0015

Inotrope score required for weaning from

CBP Mean plusmn SD 105plusmn

65 44plusmn

55 lt0001

n() Number (percentage) of patients Mean plusmnSD P-value is significant when Plt005 unpaired t

test for inotrope score P value is significant when P lt 005 Fisherrsquos exact test for spontaneous

defibrillation electrical defibrillation requirement of pacing and intraoperative inotrope

Postoperative parameters

There was a significant

difference between both studygroups as regards inotropes

required in the intensive careInotropes were required in 14

patients of hot-shot group versus24 patients of control group (Pvalue was 0015) Inotrope score

in the ICU was 754plusmn612 in hot-shot group versus 1225plusmn1032 incontrol group (P value was 0036)

Inotrope duration was 95plusmn72hrsin hot-shot group versus

149plusmn118hrs in control group (Pvalue was 0039) (Table 5)

As regards duration ofmechanical ventilation there was

no significant difference betweenboth study groups Duration ofmechanical ventilation was 67 plusmn 38

hrs in hot-shot group versus88plusmn44hrs in control group (Pvalue was 0053) (Table 5)

As regards duration of ICU

stay there was no significantdifference between both study

groups Duration of ICU stay was511plusmn188hrs in hot-shot groupversus 603plusmn231hrs in control

group (P-value was 0099) (Table

5)

There was no significantdifference between both study

groups as regards mortality Therewas no postoperative death in hot-shot group versus 3 postoperative

deaths in control group (P valuewas 0237) (Table 5)

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

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Comparison of cardioprotective effects Hussein Sabri et al

20

Table 5 Postoperative clinical outcome parametersControl

group

No =30

Hot-shot

group

No =30

P

value

Requirement of postoperative inotrope n () 24 (80) 14 (467) 0015

Inotrope score in ICU Meanplusmn SD 1225plusmn1032 754plusmn612 0036

Inotrope duration (h) Mean plusmn SD 149plusmn118 95plusmn72 0039

Duration of mechanical ventilation (h) Mean plusmn SD 88plusmn 44 67plusmn 38 0053

Duration of ICU stay (h) Mean plusmn SD 603 plusmn 231 511plusmn 188 0099

Mortality n () 3 (10) 0 (0) 0237

n () Number (percentage) of patients Mean plusmnSD P-value is significant when Plt005

unpaired t-test for inotrope score in ICU inotrope duration duration of mechanical Ventilation and duration of ICU stay P-value is significant when Plt005 Fisherrsquos exact test

for requirement of postoperative inotrope and mortality

Myocardial oxygen and lactate

extraction ratio As regards myo-

cardial oxygen extraction ratiothere was no significant differencebetween hot-shot group and

control group at the different

studied time intervals throughout

the initial sixty minutes ofreperfusion (P-value was gt005)(Table 6 Fig 1)

Table 6 Myocardial oxygen extraction ratio (MO2 ER)

Time interval after declamping of the aorta

Control

group

No =30

Hot-shot

group

No =30

P

value

M O2 ER immediately after declamping 529plusmn 62 512 plusmn 66 0308

M O2 ER 15 min after declamping 505plusmn 58 494 plusmn 61 0477

M O2 ER 30 min after declamping 492plusmn 55 480 plusmn 58 0414

M O2 ER 45 min after declamping 485plusmn 52 472 plusmn 55 0351

M O2 ER 60 min after declamping 476plusmn 51 468 plusmn 53 0554Mean plusmnSD P value is significant when P lt 005 unpaired t-test

983091983088

983091983093

983092983088

983092983093

983093983088

983093983093

983094983088

983088 983149983145983150 983089983093 983149983145983150 983091983088 983149983145983150 983092983093 983149983145983150 983094983088 983149983145983150

983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137

983117 983161 983151 983139 983137 983154 983140 983145 983137

983148 983151 983160 983161 983143 983141 983150 983141 983160 983156 983154 983137 983139 983156 983145 983151 983150 983154 983137 983156 983145 983151 983077 983139983151983150983156983154983151983148 983143983154983151983157983152

983144983151983156983085983155983144983151983156 983143983154983151983157983152

Fig 1 Myocardial oxygen extraction ratio Data are presented as mean Error bars represent

95 confidence interval

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

21

As regards myocardial lactateextraction ratio there was signi-ficant difference between hot-shotgroup and control group at the

different studied time intervals

throughout the initial sixtyminutes of reperfusion (P-valueswere 0027 0042 0024 lt0001lt0001 respectively) (Table 7

Fig 2)

Table 7 Myocardial lactate extraction ratio (M lactate ER)

Time interval after declamping of the aorta

Control

group

No =30

Hot-shot

group

No =30

P-

value

M lactate ER immediately after declamping -222plusmn 59 -190plusmn 50 0027

M lactate ER 15 min after declamping -136plusmn 50 -111plusmn 42 0042

M lactate ER 30 min after declamping -75plusmn 54 -44plusmn 49 0024

M lactate ER 45 min after declamping -48plusmn 40 00plusmn 46 lt0001

M lactate ER 60 min after declamping -26plusmn 34 59plusmn 41 lt0001

Mean plusmn SD P value is significant when Plt005 unpaired t-test

983085983091983088

983085983090983093

983085983090983088

983085983089983093

983085983089983088

983085983093

983088

983093

983089983088

983089983093

983090983088

983088 983149983145983150 983089983093 983149983145983150 983091983088 983149983145983150 983092983093 983149983145983150 983094983088 983149983145983150

983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137

983117 983161 983151 983139 983137 983154 983140 983145 983137 983148 983148 983137 983139 983156 983137 983156 983141 983141 983160 983156 983154 983137 983139 983156

983145 983151 983150 983154 983137 983156 983145 983151 983077

983139983151983150983156983154983151983148 983143983154983151983157983152

983144983151983156983085983155983144983151983156 983143983154983151983157983152

Fig 2 Myocardial lactate extraction ratio Data are presented as mean Error bars

represent 95 confidence interval P-value is significant when Plt005

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

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Comparison of cardioprotective effects Hussein Sabri et al

22

Serum level of cardiac troponinI (cTnI) There was no significantdifference between both studygroups as regards baseline values of

serum troponin I (P-value was0146) There was significantdifference between both study

groups in serum troponin I level at4 and 8 hours after declamping of

the aorta Serum troponin I level at

4 hours after declamping was132plusmn80ngml in hot-shot groupversus 313plusmn231ngml in controlgroup (P value was lt0001) Serum

troponin I level at 8 hours afterdeclamping was 100plusmn58ngml inhot-shot group versus 191plusmn115ngml in control group (P value waslt0001) (Table 8 Fig 3)

Table 8 Serum level of cardiac troponin I (cTnI)Control

group

No =30

Hot-shot

group

No =30

P

value

Baseline (ngml) 08plusmn

04 07plusmn

04 01464 hrs after declamping of the aorta (ngml) 313plusmn 231 132 plusmn 80 lt0001

8 hrs after declamping of the aorta (ngml) 191plusmn 115 100 plusmn 58 lt0001

Mean plusmn SD P-value is significant when P lt 005 unpaired t test

983088

983093

983089983088

983089983093

983090983088

983090983093

983091983088

983091983093

983092983088

983092983093

983138983137983155983141983148983145983150983141 983092 983144983154983155 983096 983144983154983155

983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137

983124 983154 983151 983152 983151 983150 983145 983150 983113 983080 983150 983143 983087 983149 983148 983081

983139983151983150983156983154983151983148 983143983154983151983157983152

983144983151983156983085983155983144983151983156 983143983154983151983157983152

Fig 3 Serum level of cardiac troponin I (cTnI) Data are presented as mean Errorbars represent 95 confidence interval P value is significant when P lt 005

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

23

Discussion

Low cardiac output aftersurgically induced ischemia andreperfusion continues to be a major

contributor to morbidity andmortality after pediatric cardiacsurgery and in more than 50 of

cases has been attributed toinadequate myocardial protection(Bull et al 1984 Hammon

1995)

Careful control of theconditions of reperfusion and the

composition of the reperfusate can

optimize postischemic recovery ofmyocardial function (Follette et

al 1981 Allen et al 1986)

The current study wasdesigned to evaluate the cardio-protective effect of using inter-mittent antegrade cold bloodcardioplegia versus intermittent

cold blood cardioplegia with ter-minal warm blood cardioplegia

(hot-shot) in pediatric cardiacpatients

The result of the current

study demonstrated significantdecrease in blood pressure at 5and 15 minutes interval in thecontrol group compared with the

hot-shot group after weaning ofthe cardiopulmonary bypass

Intermittent cold blood

cardioplegia with terminal warmblood cardioplegia offers favorable

effect on the clinical outcomeparameters This was demon-strated in this study as asignificant higher percentage ofspontaneous defibrillation into

sinus rhythm in hot-shot group

than control group (767 versus333 respectively)

The percentage of patientsrequiring inotropic support after

weaning from cardiopulmonarybypass was significantly higher incontrol group than hot-shot group

(80 versus 467 respectively)

By adopting the inotropic scoredescribed by Wernovsky et al

(1995) the level of inotropic

support was significantly lower inhot-shot group than control group

(44plusmn55 versus 105plusmn65 respec-

tively)

The improved clinical outcomerevealed the role of intermittent

cold blood cardioplegia withterminal warm blood cardioplegia inenhancement of myocardialprotection which was manifested asa reduction in myocardial arrhyth-

mia associated with ischemiareperfusion and a better myocardial

functionThe myocardial protective effect

of terminal warm blood cardioplegia

extended into the postoperativeperiod This was manifested as asignificant higher percentage ofpatients in control group than hot-

shot group who required inotropicsupport in the intensive care (80

versus 467 respectively) The

maximum dose of inotropic support(calculated by a modification of

inotropic score) was significantlyhigher in control group than hot-shot group (1225plusmn1032 versus754plusmn612 respectively) Theduration of inotropic support was

significantly higher in control group

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

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Comparison of cardioprotective effects Hussein Sabri et al

24

than hot-shot group (149plusmn118versus 95plusmn72 respectively)

In the postoperative periodresults were comparable as

regards duration of mechanicalventilation and stay in theintensive care unit in addition to

comparable mortality rate

Myocardial oxygen extraction

ratio reflects balance betweenmyocardial oxygen supply anddemand Myocardial oxygenextraction ratio was similar

between the two studied groups

This similarity may reflect theaerobic metabolic state of the

myocardium provided by the coldblood cardioplegia in both groups

Lactate release from theischemic myocytes is considered asa reflection of anaerobic metabolism(Krause et al 1993)

A negative myocardial lactateextraction ratio indicates that

amount of lactate productionthrough anaerobic glycolysis washigher than the amount of lactate

consumption for aerobic energy pro-duction with continuing anaerobicmetabolism and impairment ofnormal aerobic energy production

While a positive myocardial

lactate extraction ratio indicatesthat amount of lactate production

through anaerobic glycolysis wasless than the amount of lactate

consumption for aerobic energyproduction and that myocardiumstarts to use lactate as a substratevia oxidative phosphorylation

Myocardial lactate extractionratio in control group stayednegative value all through the sixtyminutes of studied period which

indicates impairment of aerobicmyocardial metabolism during thisperiod In hot-shot group myo-cardial lactate extraction ratioremained negative value till 45min

after declamping of the aorta when

it becomes a positive value

This point is considered a turnfrom anaerobic to aerobic meta-

bolism and it resembles the equilib-

rium between lactate consumptionand production At this point themyocardium starts to use lactate as

a substrate via oxidative phosphor-rylation (Krause et al 1993)

The results of this studydemonstrate the recovery of aerobicmetabolism afforded by inter-

mittent cold blood cardioplegia withterminal warm blood cardioplegiaTroponin I is a myocyte-contractileapparatus protein released follo-

wing myocardial damage Troponin

I Level is considered sensitivemarker of myocardial injuryassociated with cardiac surgery

(Immer et al 1998)

In this study we demonstrated

a significant increase in post-operative troponin I at 4 8 hoursafter declamping of the aorta in

control group compared to hot-shotgroup (P value was lt0001) Thisreflects the beneficial effect of warmcardioplegic reperfusion on myo-cardial outcome in reducing themyocardial damage following

ischemiareperfusion injury

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

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Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

25

In this study the composition ofterminal warm blood cardioplegiawas made to resemble the compo-sition of cold blood cardioplegia

used The point was to provide asolution with adequate potassiumconcentration to produce electro-mechanical arrest during reper-fusion This solution differs from the

conventional blood reperfusate in

presence of high potassiumconcentration (20mmolL-1) ahigher pH and a higher osmolarity

Thus cardioprotective effect ofterminal warm blood cardioplegia is

expected to be achieved byprolongation of electromechanicalarrest which reduces the energy

demands and counteracting tissueacidosis and edema therefore it

reduces the myocardial injury bypreservation and resynthesis ofhigh energy phosphates

There were small number ofclinical studies that have

examined specific myocardialprotection strategy in pediatric

population Utilizing an isolatedblood perfused neonatal heartpreparation Nomura et al

(2001) assessed the effects of

terminal warm blood cardioplegiaterminal warm oxygenated crys-talloid cardioplegia in comparisonwith conventional reperfusion(without any kind of terminal

cardioplegia) through assessmentrecovery of left ventricularfunction They demonstrated that

reperfusion with either terminalwarm blood cardioplegia or ter-

minal warm oxygenated crys-talloid cardioplegia resulted in

better recovery of myocardialfunction with slightly betterfunction in terminal warm bloodcardioplegia

In a clinically relevant intactanimal model that simulated theclinical condition of hypoxic

neonatal myocardium exposed toischemic stress Kronon et al

(2000) investigated the cardio-

protective effects of terminalwarm blood cardioplegic reper-fusion versus conventional reper-

fusion through assessment reco-

very of left ventricular systolicfunction and diastolic complianceThey showed that A warm cardio-

plegic reperfusion helps reduce

the reperfusion injury resultingin improved myocardial functionand metabolic recovery in hypoxicneonatal myocardium

Toyoda et al (2003) examined

the cardioprotective effect ofterminal warm blood cardioplegia inpediatric cardiac patients Blood

cardioplegia solution was composed

by mixing a hyperkalemic solutionwith oxygenated blood in 12dilutions with temperature 9oCThe terminal warm blood

cardioplegia had a finalconcentration of potassium 18mmolL-1 The results of Toyoda et alshowed beneficial effect of terminal

warm blood cardioplegia inreduction of myo-cardial injury Inagreement with Toyoda the

protocol of cardioplegiaadministered is almost similar asregard the concentration of pota-

ssium in terminal warm bloodcardioplegia (20mmolL-1) in 11

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1618

Comparison of cardioprotective effects Hussein Sabri et al

26

dilution (1 crystalloid 1 blood) withsimilar result in myocardial pro-tection and improvement in aerobicenergy metabolism As a marker of

myocardial necrosis the currentstudy used troponin I whichprovides comparable information astroponin T used in the study ofToyoda

The current study is inagreement with Modi et al

(2004) who compared the use of

crystalloid cardioplegia cold blood

cardioplegia and cold blood

cardioplegia with hot-shot incyanotic and acyanotic pediatricpatients undergoing surgical

correction The efficacy of the 3

techniques was assessed byexamination right ventricularbiopsy specimen before and afterreperfusion analysis of cellular

metabolites and assessment oftroponin I level Their resultdemonstrated that for cyanotic

patients blood cardioplegia withhot-shot reduced metabolic injury

compared with cold crystalloidcardioplegia They also showed

that cold blood cardioplegia wason its own better than crystalloid

but not as good as cold bloodcardioplegia with hot-shot

Young et al (1997) failed to

demonstrate statistical advantage

for blood cardioplegia over crys-talloid cardioplegia in surgery forcongenital heart The most impor-

tant aspect of the study of Younget al is that no obvious benefitcan be anticipated by use of blood

cardioplegia in congenital heartsurgery when only antegrade

hypothermia dosing technique isused The integrated cardioplegicapproach using warm cold ante-grade and retrograde technique

with substrate enrichment may bebeneficial for pediatric population

As conclusion the result of

the current study showed that theuse of cardioplegia with hot-shot

provides the criteria that mayimprove myocardial protectionand reduce myocardial injury inpediatric population

These criteria include warm

blood accelerates recovery oftemperature-dependent enzymatic

and metabolic function highpotassium concentration prolongs

electromechanical arrest to decreaseenergy demands alkaloid solutionwhich counteracts tissue acidosisand high osmolarity which coun-teracts tissue edema

References

1 Allen BS Okamoto F

Buckberg GD Bugyi H

Young H Leaf J

Beyersdorf F Sjostrand F

and Maloney JV Jr

Studies of controlledreperfusion after ischemiaXV Immediate functional

recovery after six hours of

regional ischemia by careful

control of conditions ofreperfusion and compositionof reperfusate J Thorac

Cardiovasc Surg 1986 92(3Pt 2) 621-35

2 Allen BS Current Conceptsin Pediatric Myocardial

Protection In Salerno TA and

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1718

Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

27

Ricci M (editors) MyocardialProtection 1st editionBlackwell publishing 2004207-29

3 Allen BS Pediatricmyocardial protection acardioplegic stra-tegy is the

solution Semin Thorac

Cardiovasc Surg Pediatr CardSurg Annu 2004 7 141-54

4 Bull C Cooper J and

Stark J Cardioplegicprotection of the childrsquos

heart J Thorac Cardio-vasc

Surg 1984 88(2) 287-93

5 Caputo M Dihmis WC

Bryan AJ Suleiman MS

and Angelini GD Warmblood hyperkalaemicreperfusion (hot shot)prevents myocardial substratederangement in patients

undergoing coronary arterybypass surgery Eur J

Cardiothorac Surg 199813(5) 559-64

6 Follette DM Fey K

Buckberg GD Helly JJ Jr

Steed DL Foglia RP and

Maloney JV Jr Reducingpostischemic damage by

temporary modifi-cation ofreperfusate calcium

potassium pH and

osmolarity J ThoracCardiovasc Surg 1981 82 (2)

221-38

7 Hammon JW Jr Myocardialprotection in the immatureheart Ann Thorac Surg 1995

60 (3) 839-842

8 Immer FF Stocker FP

Seiler AM Pfammatter JP

Printzen G and Carrel TP

Comparison of troponin-I and

troponin-T after pediatriccardiovascular opera-tion

Ann Thorac Surg 1998 66 (6)2073-7

9 Krause EG Pfeiffer D

Wollen-berger U and

Wollert HG Lactatemonitoring during and aftercardiopulmonary bypass an

approach implicating a peri-

operative measure for cardiacenergy metabolism In PiperHM Preusse CJ (editors)

Ischemia-reperfusion in

cardiac surgery 1st editionKluwer Academic 1993 317-33

10 Kronon MT Allen BS

Rahman S Wang T

Tayyab NA Bolling KS and

Ilbawi MN Reducingpostischemic reper-fusion

damage in neonates using a

terminal warm substrate-enriched blood cardioplegicreperfusate Ann Thorac Surg2000 70(3) 765-770

11 Modi P Suleiman MS

Reeves B Pawade A Parry

AJ Angelini GD and

Caputo M Myocardial

metabolic changes during ped-iatric cardiac surgery arando-mized study of 3cardioplegic techniques JThorac Cardiovasc Surg2004 128(1) 67-75

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1818

Comparison of cardioprotective effects Hussein Sabri et al

28

12 Nomura F Forbess JM

and Mayer EJ Effects ofHot shot on recovery afterhypothermic ischemia in

neonatal lamb heart JCardiovasc Surg (Torino)2001 42(1) 1-7

13 Teoh KH Christakis GT

Weisel RD Fremes SE

Mickle DA Romaschin AD

Harding RS Ivanov J

Madonik MM Ross IM et

al Accelerated myocardial

metabolic recovery with

terminal warm bloodcardioplegia J ThoracCardiovasc Surg 1986 91(6)

888-95

14 Toyoda Y Yamaguchi M

Yoshimura N Oka S and

Okita Y Cardioprotectiveeffects and the mechanisms of

terminal warm bloodcardioplegia in pediatriccardiac surgery J ThoracCardiovasc Surg 2003 125

(6) 1242-51

15 Wernovsky G Wypij D

Jonas RA Mayer JE Jr

Hanley FL Hickey PR

Walsh AZ Chang AC

Castaneda AR NewburgerJW et al Postoperativecourse and hemodynamicprofile after the arterial

switch operation in neo-natesand infants A comparison of

low-flow cardiopulmonarybypass and circulatory arrestCirculation 1995 92(8) 2226-

35

16 Young JN Choy IO SilvaNK Obayashi DY and

Barkan HE Antegrade cold

blood cardioplegia is not

demonstrably advan-tageousover cold crystalloidcardioplegia in surgery forcongenital heart disease J

Thorac Cardiovasc Surg1997 114(6) 1002-9

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1018

Comparison of cardioprotective effects Hussein Sabri et al

20

Table 5 Postoperative clinical outcome parametersControl

group

No =30

Hot-shot

group

No =30

P

value

Requirement of postoperative inotrope n () 24 (80) 14 (467) 0015

Inotrope score in ICU Meanplusmn SD 1225plusmn1032 754plusmn612 0036

Inotrope duration (h) Mean plusmn SD 149plusmn118 95plusmn72 0039

Duration of mechanical ventilation (h) Mean plusmn SD 88plusmn 44 67plusmn 38 0053

Duration of ICU stay (h) Mean plusmn SD 603 plusmn 231 511plusmn 188 0099

Mortality n () 3 (10) 0 (0) 0237

n () Number (percentage) of patients Mean plusmnSD P-value is significant when Plt005

unpaired t-test for inotrope score in ICU inotrope duration duration of mechanical Ventilation and duration of ICU stay P-value is significant when Plt005 Fisherrsquos exact test

for requirement of postoperative inotrope and mortality

Myocardial oxygen and lactate

extraction ratio As regards myo-

cardial oxygen extraction ratiothere was no significant differencebetween hot-shot group and

control group at the different

studied time intervals throughout

the initial sixty minutes ofreperfusion (P-value was gt005)(Table 6 Fig 1)

Table 6 Myocardial oxygen extraction ratio (MO2 ER)

Time interval after declamping of the aorta

Control

group

No =30

Hot-shot

group

No =30

P

value

M O2 ER immediately after declamping 529plusmn 62 512 plusmn 66 0308

M O2 ER 15 min after declamping 505plusmn 58 494 plusmn 61 0477

M O2 ER 30 min after declamping 492plusmn 55 480 plusmn 58 0414

M O2 ER 45 min after declamping 485plusmn 52 472 plusmn 55 0351

M O2 ER 60 min after declamping 476plusmn 51 468 plusmn 53 0554Mean plusmnSD P value is significant when P lt 005 unpaired t-test

983091983088

983091983093

983092983088

983092983093

983093983088

983093983093

983094983088

983088 983149983145983150 983089983093 983149983145983150 983091983088 983149983145983150 983092983093 983149983145983150 983094983088 983149983145983150

983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137

983117 983161 983151 983139 983137 983154 983140 983145 983137

983148 983151 983160 983161 983143 983141 983150 983141 983160 983156 983154 983137 983139 983156 983145 983151 983150 983154 983137 983156 983145 983151 983077 983139983151983150983156983154983151983148 983143983154983151983157983152

983144983151983156983085983155983144983151983156 983143983154983151983157983152

Fig 1 Myocardial oxygen extraction ratio Data are presented as mean Error bars represent

95 confidence interval

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1118

Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

21

As regards myocardial lactateextraction ratio there was signi-ficant difference between hot-shotgroup and control group at the

different studied time intervals

throughout the initial sixtyminutes of reperfusion (P-valueswere 0027 0042 0024 lt0001lt0001 respectively) (Table 7

Fig 2)

Table 7 Myocardial lactate extraction ratio (M lactate ER)

Time interval after declamping of the aorta

Control

group

No =30

Hot-shot

group

No =30

P-

value

M lactate ER immediately after declamping -222plusmn 59 -190plusmn 50 0027

M lactate ER 15 min after declamping -136plusmn 50 -111plusmn 42 0042

M lactate ER 30 min after declamping -75plusmn 54 -44plusmn 49 0024

M lactate ER 45 min after declamping -48plusmn 40 00plusmn 46 lt0001

M lactate ER 60 min after declamping -26plusmn 34 59plusmn 41 lt0001

Mean plusmn SD P value is significant when Plt005 unpaired t-test

983085983091983088

983085983090983093

983085983090983088

983085983089983093

983085983089983088

983085983093

983088

983093

983089983088

983089983093

983090983088

983088 983149983145983150 983089983093 983149983145983150 983091983088 983149983145983150 983092983093 983149983145983150 983094983088 983149983145983150

983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137

983117 983161 983151 983139 983137 983154 983140 983145 983137 983148 983148 983137 983139 983156 983137 983156 983141 983141 983160 983156 983154 983137 983139 983156

983145 983151 983150 983154 983137 983156 983145 983151 983077

983139983151983150983156983154983151983148 983143983154983151983157983152

983144983151983156983085983155983144983151983156 983143983154983151983157983152

Fig 2 Myocardial lactate extraction ratio Data are presented as mean Error bars

represent 95 confidence interval P-value is significant when Plt005

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1218

Comparison of cardioprotective effects Hussein Sabri et al

22

Serum level of cardiac troponinI (cTnI) There was no significantdifference between both studygroups as regards baseline values of

serum troponin I (P-value was0146) There was significantdifference between both study

groups in serum troponin I level at4 and 8 hours after declamping of

the aorta Serum troponin I level at

4 hours after declamping was132plusmn80ngml in hot-shot groupversus 313plusmn231ngml in controlgroup (P value was lt0001) Serum

troponin I level at 8 hours afterdeclamping was 100plusmn58ngml inhot-shot group versus 191plusmn115ngml in control group (P value waslt0001) (Table 8 Fig 3)

Table 8 Serum level of cardiac troponin I (cTnI)Control

group

No =30

Hot-shot

group

No =30

P

value

Baseline (ngml) 08plusmn

04 07plusmn

04 01464 hrs after declamping of the aorta (ngml) 313plusmn 231 132 plusmn 80 lt0001

8 hrs after declamping of the aorta (ngml) 191plusmn 115 100 plusmn 58 lt0001

Mean plusmn SD P-value is significant when P lt 005 unpaired t test

983088

983093

983089983088

983089983093

983090983088

983090983093

983091983088

983091983093

983092983088

983092983093

983138983137983155983141983148983145983150983141 983092 983144983154983155 983096 983144983154983155

983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137

983124 983154 983151 983152 983151 983150 983145 983150 983113 983080 983150 983143 983087 983149 983148 983081

983139983151983150983156983154983151983148 983143983154983151983157983152

983144983151983156983085983155983144983151983156 983143983154983151983157983152

Fig 3 Serum level of cardiac troponin I (cTnI) Data are presented as mean Errorbars represent 95 confidence interval P value is significant when P lt 005

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1318

Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

23

Discussion

Low cardiac output aftersurgically induced ischemia andreperfusion continues to be a major

contributor to morbidity andmortality after pediatric cardiacsurgery and in more than 50 of

cases has been attributed toinadequate myocardial protection(Bull et al 1984 Hammon

1995)

Careful control of theconditions of reperfusion and the

composition of the reperfusate can

optimize postischemic recovery ofmyocardial function (Follette et

al 1981 Allen et al 1986)

The current study wasdesigned to evaluate the cardio-protective effect of using inter-mittent antegrade cold bloodcardioplegia versus intermittent

cold blood cardioplegia with ter-minal warm blood cardioplegia

(hot-shot) in pediatric cardiacpatients

The result of the current

study demonstrated significantdecrease in blood pressure at 5and 15 minutes interval in thecontrol group compared with the

hot-shot group after weaning ofthe cardiopulmonary bypass

Intermittent cold blood

cardioplegia with terminal warmblood cardioplegia offers favorable

effect on the clinical outcomeparameters This was demon-strated in this study as asignificant higher percentage ofspontaneous defibrillation into

sinus rhythm in hot-shot group

than control group (767 versus333 respectively)

The percentage of patientsrequiring inotropic support after

weaning from cardiopulmonarybypass was significantly higher incontrol group than hot-shot group

(80 versus 467 respectively)

By adopting the inotropic scoredescribed by Wernovsky et al

(1995) the level of inotropic

support was significantly lower inhot-shot group than control group

(44plusmn55 versus 105plusmn65 respec-

tively)

The improved clinical outcomerevealed the role of intermittent

cold blood cardioplegia withterminal warm blood cardioplegia inenhancement of myocardialprotection which was manifested asa reduction in myocardial arrhyth-

mia associated with ischemiareperfusion and a better myocardial

functionThe myocardial protective effect

of terminal warm blood cardioplegia

extended into the postoperativeperiod This was manifested as asignificant higher percentage ofpatients in control group than hot-

shot group who required inotropicsupport in the intensive care (80

versus 467 respectively) The

maximum dose of inotropic support(calculated by a modification of

inotropic score) was significantlyhigher in control group than hot-shot group (1225plusmn1032 versus754plusmn612 respectively) Theduration of inotropic support was

significantly higher in control group

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1418

Comparison of cardioprotective effects Hussein Sabri et al

24

than hot-shot group (149plusmn118versus 95plusmn72 respectively)

In the postoperative periodresults were comparable as

regards duration of mechanicalventilation and stay in theintensive care unit in addition to

comparable mortality rate

Myocardial oxygen extraction

ratio reflects balance betweenmyocardial oxygen supply anddemand Myocardial oxygenextraction ratio was similar

between the two studied groups

This similarity may reflect theaerobic metabolic state of the

myocardium provided by the coldblood cardioplegia in both groups

Lactate release from theischemic myocytes is considered asa reflection of anaerobic metabolism(Krause et al 1993)

A negative myocardial lactateextraction ratio indicates that

amount of lactate productionthrough anaerobic glycolysis washigher than the amount of lactate

consumption for aerobic energy pro-duction with continuing anaerobicmetabolism and impairment ofnormal aerobic energy production

While a positive myocardial

lactate extraction ratio indicatesthat amount of lactate production

through anaerobic glycolysis wasless than the amount of lactate

consumption for aerobic energyproduction and that myocardiumstarts to use lactate as a substratevia oxidative phosphorylation

Myocardial lactate extractionratio in control group stayednegative value all through the sixtyminutes of studied period which

indicates impairment of aerobicmyocardial metabolism during thisperiod In hot-shot group myo-cardial lactate extraction ratioremained negative value till 45min

after declamping of the aorta when

it becomes a positive value

This point is considered a turnfrom anaerobic to aerobic meta-

bolism and it resembles the equilib-

rium between lactate consumptionand production At this point themyocardium starts to use lactate as

a substrate via oxidative phosphor-rylation (Krause et al 1993)

The results of this studydemonstrate the recovery of aerobicmetabolism afforded by inter-

mittent cold blood cardioplegia withterminal warm blood cardioplegiaTroponin I is a myocyte-contractileapparatus protein released follo-

wing myocardial damage Troponin

I Level is considered sensitivemarker of myocardial injuryassociated with cardiac surgery

(Immer et al 1998)

In this study we demonstrated

a significant increase in post-operative troponin I at 4 8 hoursafter declamping of the aorta in

control group compared to hot-shotgroup (P value was lt0001) Thisreflects the beneficial effect of warmcardioplegic reperfusion on myo-cardial outcome in reducing themyocardial damage following

ischemiareperfusion injury

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1518

Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

25

In this study the composition ofterminal warm blood cardioplegiawas made to resemble the compo-sition of cold blood cardioplegia

used The point was to provide asolution with adequate potassiumconcentration to produce electro-mechanical arrest during reper-fusion This solution differs from the

conventional blood reperfusate in

presence of high potassiumconcentration (20mmolL-1) ahigher pH and a higher osmolarity

Thus cardioprotective effect ofterminal warm blood cardioplegia is

expected to be achieved byprolongation of electromechanicalarrest which reduces the energy

demands and counteracting tissueacidosis and edema therefore it

reduces the myocardial injury bypreservation and resynthesis ofhigh energy phosphates

There were small number ofclinical studies that have

examined specific myocardialprotection strategy in pediatric

population Utilizing an isolatedblood perfused neonatal heartpreparation Nomura et al

(2001) assessed the effects of

terminal warm blood cardioplegiaterminal warm oxygenated crys-talloid cardioplegia in comparisonwith conventional reperfusion(without any kind of terminal

cardioplegia) through assessmentrecovery of left ventricularfunction They demonstrated that

reperfusion with either terminalwarm blood cardioplegia or ter-

minal warm oxygenated crys-talloid cardioplegia resulted in

better recovery of myocardialfunction with slightly betterfunction in terminal warm bloodcardioplegia

In a clinically relevant intactanimal model that simulated theclinical condition of hypoxic

neonatal myocardium exposed toischemic stress Kronon et al

(2000) investigated the cardio-

protective effects of terminalwarm blood cardioplegic reper-fusion versus conventional reper-

fusion through assessment reco-

very of left ventricular systolicfunction and diastolic complianceThey showed that A warm cardio-

plegic reperfusion helps reduce

the reperfusion injury resultingin improved myocardial functionand metabolic recovery in hypoxicneonatal myocardium

Toyoda et al (2003) examined

the cardioprotective effect ofterminal warm blood cardioplegia inpediatric cardiac patients Blood

cardioplegia solution was composed

by mixing a hyperkalemic solutionwith oxygenated blood in 12dilutions with temperature 9oCThe terminal warm blood

cardioplegia had a finalconcentration of potassium 18mmolL-1 The results of Toyoda et alshowed beneficial effect of terminal

warm blood cardioplegia inreduction of myo-cardial injury Inagreement with Toyoda the

protocol of cardioplegiaadministered is almost similar asregard the concentration of pota-

ssium in terminal warm bloodcardioplegia (20mmolL-1) in 11

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1618

Comparison of cardioprotective effects Hussein Sabri et al

26

dilution (1 crystalloid 1 blood) withsimilar result in myocardial pro-tection and improvement in aerobicenergy metabolism As a marker of

myocardial necrosis the currentstudy used troponin I whichprovides comparable information astroponin T used in the study ofToyoda

The current study is inagreement with Modi et al

(2004) who compared the use of

crystalloid cardioplegia cold blood

cardioplegia and cold blood

cardioplegia with hot-shot incyanotic and acyanotic pediatricpatients undergoing surgical

correction The efficacy of the 3

techniques was assessed byexamination right ventricularbiopsy specimen before and afterreperfusion analysis of cellular

metabolites and assessment oftroponin I level Their resultdemonstrated that for cyanotic

patients blood cardioplegia withhot-shot reduced metabolic injury

compared with cold crystalloidcardioplegia They also showed

that cold blood cardioplegia wason its own better than crystalloid

but not as good as cold bloodcardioplegia with hot-shot

Young et al (1997) failed to

demonstrate statistical advantage

for blood cardioplegia over crys-talloid cardioplegia in surgery forcongenital heart The most impor-

tant aspect of the study of Younget al is that no obvious benefitcan be anticipated by use of blood

cardioplegia in congenital heartsurgery when only antegrade

hypothermia dosing technique isused The integrated cardioplegicapproach using warm cold ante-grade and retrograde technique

with substrate enrichment may bebeneficial for pediatric population

As conclusion the result of

the current study showed that theuse of cardioplegia with hot-shot

provides the criteria that mayimprove myocardial protectionand reduce myocardial injury inpediatric population

These criteria include warm

blood accelerates recovery oftemperature-dependent enzymatic

and metabolic function highpotassium concentration prolongs

electromechanical arrest to decreaseenergy demands alkaloid solutionwhich counteracts tissue acidosisand high osmolarity which coun-teracts tissue edema

References

1 Allen BS Okamoto F

Buckberg GD Bugyi H

Young H Leaf J

Beyersdorf F Sjostrand F

and Maloney JV Jr

Studies of controlledreperfusion after ischemiaXV Immediate functional

recovery after six hours of

regional ischemia by careful

control of conditions ofreperfusion and compositionof reperfusate J Thorac

Cardiovasc Surg 1986 92(3Pt 2) 621-35

2 Allen BS Current Conceptsin Pediatric Myocardial

Protection In Salerno TA and

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1718

Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

27

Ricci M (editors) MyocardialProtection 1st editionBlackwell publishing 2004207-29

3 Allen BS Pediatricmyocardial protection acardioplegic stra-tegy is the

solution Semin Thorac

Cardiovasc Surg Pediatr CardSurg Annu 2004 7 141-54

4 Bull C Cooper J and

Stark J Cardioplegicprotection of the childrsquos

heart J Thorac Cardio-vasc

Surg 1984 88(2) 287-93

5 Caputo M Dihmis WC

Bryan AJ Suleiman MS

and Angelini GD Warmblood hyperkalaemicreperfusion (hot shot)prevents myocardial substratederangement in patients

undergoing coronary arterybypass surgery Eur J

Cardiothorac Surg 199813(5) 559-64

6 Follette DM Fey K

Buckberg GD Helly JJ Jr

Steed DL Foglia RP and

Maloney JV Jr Reducingpostischemic damage by

temporary modifi-cation ofreperfusate calcium

potassium pH and

osmolarity J ThoracCardiovasc Surg 1981 82 (2)

221-38

7 Hammon JW Jr Myocardialprotection in the immatureheart Ann Thorac Surg 1995

60 (3) 839-842

8 Immer FF Stocker FP

Seiler AM Pfammatter JP

Printzen G and Carrel TP

Comparison of troponin-I and

troponin-T after pediatriccardiovascular opera-tion

Ann Thorac Surg 1998 66 (6)2073-7

9 Krause EG Pfeiffer D

Wollen-berger U and

Wollert HG Lactatemonitoring during and aftercardiopulmonary bypass an

approach implicating a peri-

operative measure for cardiacenergy metabolism In PiperHM Preusse CJ (editors)

Ischemia-reperfusion in

cardiac surgery 1st editionKluwer Academic 1993 317-33

10 Kronon MT Allen BS

Rahman S Wang T

Tayyab NA Bolling KS and

Ilbawi MN Reducingpostischemic reper-fusion

damage in neonates using a

terminal warm substrate-enriched blood cardioplegicreperfusate Ann Thorac Surg2000 70(3) 765-770

11 Modi P Suleiman MS

Reeves B Pawade A Parry

AJ Angelini GD and

Caputo M Myocardial

metabolic changes during ped-iatric cardiac surgery arando-mized study of 3cardioplegic techniques JThorac Cardiovasc Surg2004 128(1) 67-75

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1818

Comparison of cardioprotective effects Hussein Sabri et al

28

12 Nomura F Forbess JM

and Mayer EJ Effects ofHot shot on recovery afterhypothermic ischemia in

neonatal lamb heart JCardiovasc Surg (Torino)2001 42(1) 1-7

13 Teoh KH Christakis GT

Weisel RD Fremes SE

Mickle DA Romaschin AD

Harding RS Ivanov J

Madonik MM Ross IM et

al Accelerated myocardial

metabolic recovery with

terminal warm bloodcardioplegia J ThoracCardiovasc Surg 1986 91(6)

888-95

14 Toyoda Y Yamaguchi M

Yoshimura N Oka S and

Okita Y Cardioprotectiveeffects and the mechanisms of

terminal warm bloodcardioplegia in pediatriccardiac surgery J ThoracCardiovasc Surg 2003 125

(6) 1242-51

15 Wernovsky G Wypij D

Jonas RA Mayer JE Jr

Hanley FL Hickey PR

Walsh AZ Chang AC

Castaneda AR NewburgerJW et al Postoperativecourse and hemodynamicprofile after the arterial

switch operation in neo-natesand infants A comparison of

low-flow cardiopulmonarybypass and circulatory arrestCirculation 1995 92(8) 2226-

35

16 Young JN Choy IO SilvaNK Obayashi DY and

Barkan HE Antegrade cold

blood cardioplegia is not

demonstrably advan-tageousover cold crystalloidcardioplegia in surgery forcongenital heart disease J

Thorac Cardiovasc Surg1997 114(6) 1002-9

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1118

Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

21

As regards myocardial lactateextraction ratio there was signi-ficant difference between hot-shotgroup and control group at the

different studied time intervals

throughout the initial sixtyminutes of reperfusion (P-valueswere 0027 0042 0024 lt0001lt0001 respectively) (Table 7

Fig 2)

Table 7 Myocardial lactate extraction ratio (M lactate ER)

Time interval after declamping of the aorta

Control

group

No =30

Hot-shot

group

No =30

P-

value

M lactate ER immediately after declamping -222plusmn 59 -190plusmn 50 0027

M lactate ER 15 min after declamping -136plusmn 50 -111plusmn 42 0042

M lactate ER 30 min after declamping -75plusmn 54 -44plusmn 49 0024

M lactate ER 45 min after declamping -48plusmn 40 00plusmn 46 lt0001

M lactate ER 60 min after declamping -26plusmn 34 59plusmn 41 lt0001

Mean plusmn SD P value is significant when Plt005 unpaired t-test

983085983091983088

983085983090983093

983085983090983088

983085983089983093

983085983089983088

983085983093

983088

983093

983089983088

983089983093

983090983088

983088 983149983145983150 983089983093 983149983145983150 983091983088 983149983145983150 983092983093 983149983145983150 983094983088 983149983145983150

983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137

983117 983161 983151 983139 983137 983154 983140 983145 983137 983148 983148 983137 983139 983156 983137 983156 983141 983141 983160 983156 983154 983137 983139 983156

983145 983151 983150 983154 983137 983156 983145 983151 983077

983139983151983150983156983154983151983148 983143983154983151983157983152

983144983151983156983085983155983144983151983156 983143983154983151983157983152

Fig 2 Myocardial lactate extraction ratio Data are presented as mean Error bars

represent 95 confidence interval P-value is significant when Plt005

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1218

Comparison of cardioprotective effects Hussein Sabri et al

22

Serum level of cardiac troponinI (cTnI) There was no significantdifference between both studygroups as regards baseline values of

serum troponin I (P-value was0146) There was significantdifference between both study

groups in serum troponin I level at4 and 8 hours after declamping of

the aorta Serum troponin I level at

4 hours after declamping was132plusmn80ngml in hot-shot groupversus 313plusmn231ngml in controlgroup (P value was lt0001) Serum

troponin I level at 8 hours afterdeclamping was 100plusmn58ngml inhot-shot group versus 191plusmn115ngml in control group (P value waslt0001) (Table 8 Fig 3)

Table 8 Serum level of cardiac troponin I (cTnI)Control

group

No =30

Hot-shot

group

No =30

P

value

Baseline (ngml) 08plusmn

04 07plusmn

04 01464 hrs after declamping of the aorta (ngml) 313plusmn 231 132 plusmn 80 lt0001

8 hrs after declamping of the aorta (ngml) 191plusmn 115 100 plusmn 58 lt0001

Mean plusmn SD P-value is significant when P lt 005 unpaired t test

983088

983093

983089983088

983089983093

983090983088

983090983093

983091983088

983091983093

983092983088

983092983093

983138983137983155983141983148983145983150983141 983092 983144983154983155 983096 983144983154983155

983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137

983124 983154 983151 983152 983151 983150 983145 983150 983113 983080 983150 983143 983087 983149 983148 983081

983139983151983150983156983154983151983148 983143983154983151983157983152

983144983151983156983085983155983144983151983156 983143983154983151983157983152

Fig 3 Serum level of cardiac troponin I (cTnI) Data are presented as mean Errorbars represent 95 confidence interval P value is significant when P lt 005

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1318

Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

23

Discussion

Low cardiac output aftersurgically induced ischemia andreperfusion continues to be a major

contributor to morbidity andmortality after pediatric cardiacsurgery and in more than 50 of

cases has been attributed toinadequate myocardial protection(Bull et al 1984 Hammon

1995)

Careful control of theconditions of reperfusion and the

composition of the reperfusate can

optimize postischemic recovery ofmyocardial function (Follette et

al 1981 Allen et al 1986)

The current study wasdesigned to evaluate the cardio-protective effect of using inter-mittent antegrade cold bloodcardioplegia versus intermittent

cold blood cardioplegia with ter-minal warm blood cardioplegia

(hot-shot) in pediatric cardiacpatients

The result of the current

study demonstrated significantdecrease in blood pressure at 5and 15 minutes interval in thecontrol group compared with the

hot-shot group after weaning ofthe cardiopulmonary bypass

Intermittent cold blood

cardioplegia with terminal warmblood cardioplegia offers favorable

effect on the clinical outcomeparameters This was demon-strated in this study as asignificant higher percentage ofspontaneous defibrillation into

sinus rhythm in hot-shot group

than control group (767 versus333 respectively)

The percentage of patientsrequiring inotropic support after

weaning from cardiopulmonarybypass was significantly higher incontrol group than hot-shot group

(80 versus 467 respectively)

By adopting the inotropic scoredescribed by Wernovsky et al

(1995) the level of inotropic

support was significantly lower inhot-shot group than control group

(44plusmn55 versus 105plusmn65 respec-

tively)

The improved clinical outcomerevealed the role of intermittent

cold blood cardioplegia withterminal warm blood cardioplegia inenhancement of myocardialprotection which was manifested asa reduction in myocardial arrhyth-

mia associated with ischemiareperfusion and a better myocardial

functionThe myocardial protective effect

of terminal warm blood cardioplegia

extended into the postoperativeperiod This was manifested as asignificant higher percentage ofpatients in control group than hot-

shot group who required inotropicsupport in the intensive care (80

versus 467 respectively) The

maximum dose of inotropic support(calculated by a modification of

inotropic score) was significantlyhigher in control group than hot-shot group (1225plusmn1032 versus754plusmn612 respectively) Theduration of inotropic support was

significantly higher in control group

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1418

Comparison of cardioprotective effects Hussein Sabri et al

24

than hot-shot group (149plusmn118versus 95plusmn72 respectively)

In the postoperative periodresults were comparable as

regards duration of mechanicalventilation and stay in theintensive care unit in addition to

comparable mortality rate

Myocardial oxygen extraction

ratio reflects balance betweenmyocardial oxygen supply anddemand Myocardial oxygenextraction ratio was similar

between the two studied groups

This similarity may reflect theaerobic metabolic state of the

myocardium provided by the coldblood cardioplegia in both groups

Lactate release from theischemic myocytes is considered asa reflection of anaerobic metabolism(Krause et al 1993)

A negative myocardial lactateextraction ratio indicates that

amount of lactate productionthrough anaerobic glycolysis washigher than the amount of lactate

consumption for aerobic energy pro-duction with continuing anaerobicmetabolism and impairment ofnormal aerobic energy production

While a positive myocardial

lactate extraction ratio indicatesthat amount of lactate production

through anaerobic glycolysis wasless than the amount of lactate

consumption for aerobic energyproduction and that myocardiumstarts to use lactate as a substratevia oxidative phosphorylation

Myocardial lactate extractionratio in control group stayednegative value all through the sixtyminutes of studied period which

indicates impairment of aerobicmyocardial metabolism during thisperiod In hot-shot group myo-cardial lactate extraction ratioremained negative value till 45min

after declamping of the aorta when

it becomes a positive value

This point is considered a turnfrom anaerobic to aerobic meta-

bolism and it resembles the equilib-

rium between lactate consumptionand production At this point themyocardium starts to use lactate as

a substrate via oxidative phosphor-rylation (Krause et al 1993)

The results of this studydemonstrate the recovery of aerobicmetabolism afforded by inter-

mittent cold blood cardioplegia withterminal warm blood cardioplegiaTroponin I is a myocyte-contractileapparatus protein released follo-

wing myocardial damage Troponin

I Level is considered sensitivemarker of myocardial injuryassociated with cardiac surgery

(Immer et al 1998)

In this study we demonstrated

a significant increase in post-operative troponin I at 4 8 hoursafter declamping of the aorta in

control group compared to hot-shotgroup (P value was lt0001) Thisreflects the beneficial effect of warmcardioplegic reperfusion on myo-cardial outcome in reducing themyocardial damage following

ischemiareperfusion injury

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1518

Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

25

In this study the composition ofterminal warm blood cardioplegiawas made to resemble the compo-sition of cold blood cardioplegia

used The point was to provide asolution with adequate potassiumconcentration to produce electro-mechanical arrest during reper-fusion This solution differs from the

conventional blood reperfusate in

presence of high potassiumconcentration (20mmolL-1) ahigher pH and a higher osmolarity

Thus cardioprotective effect ofterminal warm blood cardioplegia is

expected to be achieved byprolongation of electromechanicalarrest which reduces the energy

demands and counteracting tissueacidosis and edema therefore it

reduces the myocardial injury bypreservation and resynthesis ofhigh energy phosphates

There were small number ofclinical studies that have

examined specific myocardialprotection strategy in pediatric

population Utilizing an isolatedblood perfused neonatal heartpreparation Nomura et al

(2001) assessed the effects of

terminal warm blood cardioplegiaterminal warm oxygenated crys-talloid cardioplegia in comparisonwith conventional reperfusion(without any kind of terminal

cardioplegia) through assessmentrecovery of left ventricularfunction They demonstrated that

reperfusion with either terminalwarm blood cardioplegia or ter-

minal warm oxygenated crys-talloid cardioplegia resulted in

better recovery of myocardialfunction with slightly betterfunction in terminal warm bloodcardioplegia

In a clinically relevant intactanimal model that simulated theclinical condition of hypoxic

neonatal myocardium exposed toischemic stress Kronon et al

(2000) investigated the cardio-

protective effects of terminalwarm blood cardioplegic reper-fusion versus conventional reper-

fusion through assessment reco-

very of left ventricular systolicfunction and diastolic complianceThey showed that A warm cardio-

plegic reperfusion helps reduce

the reperfusion injury resultingin improved myocardial functionand metabolic recovery in hypoxicneonatal myocardium

Toyoda et al (2003) examined

the cardioprotective effect ofterminal warm blood cardioplegia inpediatric cardiac patients Blood

cardioplegia solution was composed

by mixing a hyperkalemic solutionwith oxygenated blood in 12dilutions with temperature 9oCThe terminal warm blood

cardioplegia had a finalconcentration of potassium 18mmolL-1 The results of Toyoda et alshowed beneficial effect of terminal

warm blood cardioplegia inreduction of myo-cardial injury Inagreement with Toyoda the

protocol of cardioplegiaadministered is almost similar asregard the concentration of pota-

ssium in terminal warm bloodcardioplegia (20mmolL-1) in 11

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Comparison of cardioprotective effects Hussein Sabri et al

26

dilution (1 crystalloid 1 blood) withsimilar result in myocardial pro-tection and improvement in aerobicenergy metabolism As a marker of

myocardial necrosis the currentstudy used troponin I whichprovides comparable information astroponin T used in the study ofToyoda

The current study is inagreement with Modi et al

(2004) who compared the use of

crystalloid cardioplegia cold blood

cardioplegia and cold blood

cardioplegia with hot-shot incyanotic and acyanotic pediatricpatients undergoing surgical

correction The efficacy of the 3

techniques was assessed byexamination right ventricularbiopsy specimen before and afterreperfusion analysis of cellular

metabolites and assessment oftroponin I level Their resultdemonstrated that for cyanotic

patients blood cardioplegia withhot-shot reduced metabolic injury

compared with cold crystalloidcardioplegia They also showed

that cold blood cardioplegia wason its own better than crystalloid

but not as good as cold bloodcardioplegia with hot-shot

Young et al (1997) failed to

demonstrate statistical advantage

for blood cardioplegia over crys-talloid cardioplegia in surgery forcongenital heart The most impor-

tant aspect of the study of Younget al is that no obvious benefitcan be anticipated by use of blood

cardioplegia in congenital heartsurgery when only antegrade

hypothermia dosing technique isused The integrated cardioplegicapproach using warm cold ante-grade and retrograde technique

with substrate enrichment may bebeneficial for pediatric population

As conclusion the result of

the current study showed that theuse of cardioplegia with hot-shot

provides the criteria that mayimprove myocardial protectionand reduce myocardial injury inpediatric population

These criteria include warm

blood accelerates recovery oftemperature-dependent enzymatic

and metabolic function highpotassium concentration prolongs

electromechanical arrest to decreaseenergy demands alkaloid solutionwhich counteracts tissue acidosisand high osmolarity which coun-teracts tissue edema

References

1 Allen BS Okamoto F

Buckberg GD Bugyi H

Young H Leaf J

Beyersdorf F Sjostrand F

and Maloney JV Jr

Studies of controlledreperfusion after ischemiaXV Immediate functional

recovery after six hours of

regional ischemia by careful

control of conditions ofreperfusion and compositionof reperfusate J Thorac

Cardiovasc Surg 1986 92(3Pt 2) 621-35

2 Allen BS Current Conceptsin Pediatric Myocardial

Protection In Salerno TA and

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httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1718

Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

27

Ricci M (editors) MyocardialProtection 1st editionBlackwell publishing 2004207-29

3 Allen BS Pediatricmyocardial protection acardioplegic stra-tegy is the

solution Semin Thorac

Cardiovasc Surg Pediatr CardSurg Annu 2004 7 141-54

4 Bull C Cooper J and

Stark J Cardioplegicprotection of the childrsquos

heart J Thorac Cardio-vasc

Surg 1984 88(2) 287-93

5 Caputo M Dihmis WC

Bryan AJ Suleiman MS

and Angelini GD Warmblood hyperkalaemicreperfusion (hot shot)prevents myocardial substratederangement in patients

undergoing coronary arterybypass surgery Eur J

Cardiothorac Surg 199813(5) 559-64

6 Follette DM Fey K

Buckberg GD Helly JJ Jr

Steed DL Foglia RP and

Maloney JV Jr Reducingpostischemic damage by

temporary modifi-cation ofreperfusate calcium

potassium pH and

osmolarity J ThoracCardiovasc Surg 1981 82 (2)

221-38

7 Hammon JW Jr Myocardialprotection in the immatureheart Ann Thorac Surg 1995

60 (3) 839-842

8 Immer FF Stocker FP

Seiler AM Pfammatter JP

Printzen G and Carrel TP

Comparison of troponin-I and

troponin-T after pediatriccardiovascular opera-tion

Ann Thorac Surg 1998 66 (6)2073-7

9 Krause EG Pfeiffer D

Wollen-berger U and

Wollert HG Lactatemonitoring during and aftercardiopulmonary bypass an

approach implicating a peri-

operative measure for cardiacenergy metabolism In PiperHM Preusse CJ (editors)

Ischemia-reperfusion in

cardiac surgery 1st editionKluwer Academic 1993 317-33

10 Kronon MT Allen BS

Rahman S Wang T

Tayyab NA Bolling KS and

Ilbawi MN Reducingpostischemic reper-fusion

damage in neonates using a

terminal warm substrate-enriched blood cardioplegicreperfusate Ann Thorac Surg2000 70(3) 765-770

11 Modi P Suleiman MS

Reeves B Pawade A Parry

AJ Angelini GD and

Caputo M Myocardial

metabolic changes during ped-iatric cardiac surgery arando-mized study of 3cardioplegic techniques JThorac Cardiovasc Surg2004 128(1) 67-75

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1818

Comparison of cardioprotective effects Hussein Sabri et al

28

12 Nomura F Forbess JM

and Mayer EJ Effects ofHot shot on recovery afterhypothermic ischemia in

neonatal lamb heart JCardiovasc Surg (Torino)2001 42(1) 1-7

13 Teoh KH Christakis GT

Weisel RD Fremes SE

Mickle DA Romaschin AD

Harding RS Ivanov J

Madonik MM Ross IM et

al Accelerated myocardial

metabolic recovery with

terminal warm bloodcardioplegia J ThoracCardiovasc Surg 1986 91(6)

888-95

14 Toyoda Y Yamaguchi M

Yoshimura N Oka S and

Okita Y Cardioprotectiveeffects and the mechanisms of

terminal warm bloodcardioplegia in pediatriccardiac surgery J ThoracCardiovasc Surg 2003 125

(6) 1242-51

15 Wernovsky G Wypij D

Jonas RA Mayer JE Jr

Hanley FL Hickey PR

Walsh AZ Chang AC

Castaneda AR NewburgerJW et al Postoperativecourse and hemodynamicprofile after the arterial

switch operation in neo-natesand infants A comparison of

low-flow cardiopulmonarybypass and circulatory arrestCirculation 1995 92(8) 2226-

35

16 Young JN Choy IO SilvaNK Obayashi DY and

Barkan HE Antegrade cold

blood cardioplegia is not

demonstrably advan-tageousover cold crystalloidcardioplegia in surgery forcongenital heart disease J

Thorac Cardiovasc Surg1997 114(6) 1002-9

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1218

Comparison of cardioprotective effects Hussein Sabri et al

22

Serum level of cardiac troponinI (cTnI) There was no significantdifference between both studygroups as regards baseline values of

serum troponin I (P-value was0146) There was significantdifference between both study

groups in serum troponin I level at4 and 8 hours after declamping of

the aorta Serum troponin I level at

4 hours after declamping was132plusmn80ngml in hot-shot groupversus 313plusmn231ngml in controlgroup (P value was lt0001) Serum

troponin I level at 8 hours afterdeclamping was 100plusmn58ngml inhot-shot group versus 191plusmn115ngml in control group (P value waslt0001) (Table 8 Fig 3)

Table 8 Serum level of cardiac troponin I (cTnI)Control

group

No =30

Hot-shot

group

No =30

P

value

Baseline (ngml) 08plusmn

04 07plusmn

04 01464 hrs after declamping of the aorta (ngml) 313plusmn 231 132 plusmn 80 lt0001

8 hrs after declamping of the aorta (ngml) 191plusmn 115 100 plusmn 58 lt0001

Mean plusmn SD P-value is significant when P lt 005 unpaired t test

983088

983093

983089983088

983089983093

983090983088

983090983093

983091983088

983091983093

983092983088

983092983093

983138983137983155983141983148983145983150983141 983092 983144983154983155 983096 983144983154983155

983124983145983149983141 983145983150983156983141983154983158983137983148 983137983142983156983141983154 983140983141983139983148983137983149983152983145983150983143 983151983142 983156983144983141 983137983151983154983156983137

983124 983154 983151 983152 983151 983150 983145 983150 983113 983080 983150 983143 983087 983149 983148 983081

983139983151983150983156983154983151983148 983143983154983151983157983152

983144983151983156983085983155983144983151983156 983143983154983151983157983152

Fig 3 Serum level of cardiac troponin I (cTnI) Data are presented as mean Errorbars represent 95 confidence interval P value is significant when P lt 005

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1318

Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

23

Discussion

Low cardiac output aftersurgically induced ischemia andreperfusion continues to be a major

contributor to morbidity andmortality after pediatric cardiacsurgery and in more than 50 of

cases has been attributed toinadequate myocardial protection(Bull et al 1984 Hammon

1995)

Careful control of theconditions of reperfusion and the

composition of the reperfusate can

optimize postischemic recovery ofmyocardial function (Follette et

al 1981 Allen et al 1986)

The current study wasdesigned to evaluate the cardio-protective effect of using inter-mittent antegrade cold bloodcardioplegia versus intermittent

cold blood cardioplegia with ter-minal warm blood cardioplegia

(hot-shot) in pediatric cardiacpatients

The result of the current

study demonstrated significantdecrease in blood pressure at 5and 15 minutes interval in thecontrol group compared with the

hot-shot group after weaning ofthe cardiopulmonary bypass

Intermittent cold blood

cardioplegia with terminal warmblood cardioplegia offers favorable

effect on the clinical outcomeparameters This was demon-strated in this study as asignificant higher percentage ofspontaneous defibrillation into

sinus rhythm in hot-shot group

than control group (767 versus333 respectively)

The percentage of patientsrequiring inotropic support after

weaning from cardiopulmonarybypass was significantly higher incontrol group than hot-shot group

(80 versus 467 respectively)

By adopting the inotropic scoredescribed by Wernovsky et al

(1995) the level of inotropic

support was significantly lower inhot-shot group than control group

(44plusmn55 versus 105plusmn65 respec-

tively)

The improved clinical outcomerevealed the role of intermittent

cold blood cardioplegia withterminal warm blood cardioplegia inenhancement of myocardialprotection which was manifested asa reduction in myocardial arrhyth-

mia associated with ischemiareperfusion and a better myocardial

functionThe myocardial protective effect

of terminal warm blood cardioplegia

extended into the postoperativeperiod This was manifested as asignificant higher percentage ofpatients in control group than hot-

shot group who required inotropicsupport in the intensive care (80

versus 467 respectively) The

maximum dose of inotropic support(calculated by a modification of

inotropic score) was significantlyhigher in control group than hot-shot group (1225plusmn1032 versus754plusmn612 respectively) Theduration of inotropic support was

significantly higher in control group

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1418

Comparison of cardioprotective effects Hussein Sabri et al

24

than hot-shot group (149plusmn118versus 95plusmn72 respectively)

In the postoperative periodresults were comparable as

regards duration of mechanicalventilation and stay in theintensive care unit in addition to

comparable mortality rate

Myocardial oxygen extraction

ratio reflects balance betweenmyocardial oxygen supply anddemand Myocardial oxygenextraction ratio was similar

between the two studied groups

This similarity may reflect theaerobic metabolic state of the

myocardium provided by the coldblood cardioplegia in both groups

Lactate release from theischemic myocytes is considered asa reflection of anaerobic metabolism(Krause et al 1993)

A negative myocardial lactateextraction ratio indicates that

amount of lactate productionthrough anaerobic glycolysis washigher than the amount of lactate

consumption for aerobic energy pro-duction with continuing anaerobicmetabolism and impairment ofnormal aerobic energy production

While a positive myocardial

lactate extraction ratio indicatesthat amount of lactate production

through anaerobic glycolysis wasless than the amount of lactate

consumption for aerobic energyproduction and that myocardiumstarts to use lactate as a substratevia oxidative phosphorylation

Myocardial lactate extractionratio in control group stayednegative value all through the sixtyminutes of studied period which

indicates impairment of aerobicmyocardial metabolism during thisperiod In hot-shot group myo-cardial lactate extraction ratioremained negative value till 45min

after declamping of the aorta when

it becomes a positive value

This point is considered a turnfrom anaerobic to aerobic meta-

bolism and it resembles the equilib-

rium between lactate consumptionand production At this point themyocardium starts to use lactate as

a substrate via oxidative phosphor-rylation (Krause et al 1993)

The results of this studydemonstrate the recovery of aerobicmetabolism afforded by inter-

mittent cold blood cardioplegia withterminal warm blood cardioplegiaTroponin I is a myocyte-contractileapparatus protein released follo-

wing myocardial damage Troponin

I Level is considered sensitivemarker of myocardial injuryassociated with cardiac surgery

(Immer et al 1998)

In this study we demonstrated

a significant increase in post-operative troponin I at 4 8 hoursafter declamping of the aorta in

control group compared to hot-shotgroup (P value was lt0001) Thisreflects the beneficial effect of warmcardioplegic reperfusion on myo-cardial outcome in reducing themyocardial damage following

ischemiareperfusion injury

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1518

Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

25

In this study the composition ofterminal warm blood cardioplegiawas made to resemble the compo-sition of cold blood cardioplegia

used The point was to provide asolution with adequate potassiumconcentration to produce electro-mechanical arrest during reper-fusion This solution differs from the

conventional blood reperfusate in

presence of high potassiumconcentration (20mmolL-1) ahigher pH and a higher osmolarity

Thus cardioprotective effect ofterminal warm blood cardioplegia is

expected to be achieved byprolongation of electromechanicalarrest which reduces the energy

demands and counteracting tissueacidosis and edema therefore it

reduces the myocardial injury bypreservation and resynthesis ofhigh energy phosphates

There were small number ofclinical studies that have

examined specific myocardialprotection strategy in pediatric

population Utilizing an isolatedblood perfused neonatal heartpreparation Nomura et al

(2001) assessed the effects of

terminal warm blood cardioplegiaterminal warm oxygenated crys-talloid cardioplegia in comparisonwith conventional reperfusion(without any kind of terminal

cardioplegia) through assessmentrecovery of left ventricularfunction They demonstrated that

reperfusion with either terminalwarm blood cardioplegia or ter-

minal warm oxygenated crys-talloid cardioplegia resulted in

better recovery of myocardialfunction with slightly betterfunction in terminal warm bloodcardioplegia

In a clinically relevant intactanimal model that simulated theclinical condition of hypoxic

neonatal myocardium exposed toischemic stress Kronon et al

(2000) investigated the cardio-

protective effects of terminalwarm blood cardioplegic reper-fusion versus conventional reper-

fusion through assessment reco-

very of left ventricular systolicfunction and diastolic complianceThey showed that A warm cardio-

plegic reperfusion helps reduce

the reperfusion injury resultingin improved myocardial functionand metabolic recovery in hypoxicneonatal myocardium

Toyoda et al (2003) examined

the cardioprotective effect ofterminal warm blood cardioplegia inpediatric cardiac patients Blood

cardioplegia solution was composed

by mixing a hyperkalemic solutionwith oxygenated blood in 12dilutions with temperature 9oCThe terminal warm blood

cardioplegia had a finalconcentration of potassium 18mmolL-1 The results of Toyoda et alshowed beneficial effect of terminal

warm blood cardioplegia inreduction of myo-cardial injury Inagreement with Toyoda the

protocol of cardioplegiaadministered is almost similar asregard the concentration of pota-

ssium in terminal warm bloodcardioplegia (20mmolL-1) in 11

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1618

Comparison of cardioprotective effects Hussein Sabri et al

26

dilution (1 crystalloid 1 blood) withsimilar result in myocardial pro-tection and improvement in aerobicenergy metabolism As a marker of

myocardial necrosis the currentstudy used troponin I whichprovides comparable information astroponin T used in the study ofToyoda

The current study is inagreement with Modi et al

(2004) who compared the use of

crystalloid cardioplegia cold blood

cardioplegia and cold blood

cardioplegia with hot-shot incyanotic and acyanotic pediatricpatients undergoing surgical

correction The efficacy of the 3

techniques was assessed byexamination right ventricularbiopsy specimen before and afterreperfusion analysis of cellular

metabolites and assessment oftroponin I level Their resultdemonstrated that for cyanotic

patients blood cardioplegia withhot-shot reduced metabolic injury

compared with cold crystalloidcardioplegia They also showed

that cold blood cardioplegia wason its own better than crystalloid

but not as good as cold bloodcardioplegia with hot-shot

Young et al (1997) failed to

demonstrate statistical advantage

for blood cardioplegia over crys-talloid cardioplegia in surgery forcongenital heart The most impor-

tant aspect of the study of Younget al is that no obvious benefitcan be anticipated by use of blood

cardioplegia in congenital heartsurgery when only antegrade

hypothermia dosing technique isused The integrated cardioplegicapproach using warm cold ante-grade and retrograde technique

with substrate enrichment may bebeneficial for pediatric population

As conclusion the result of

the current study showed that theuse of cardioplegia with hot-shot

provides the criteria that mayimprove myocardial protectionand reduce myocardial injury inpediatric population

These criteria include warm

blood accelerates recovery oftemperature-dependent enzymatic

and metabolic function highpotassium concentration prolongs

electromechanical arrest to decreaseenergy demands alkaloid solutionwhich counteracts tissue acidosisand high osmolarity which coun-teracts tissue edema

References

1 Allen BS Okamoto F

Buckberg GD Bugyi H

Young H Leaf J

Beyersdorf F Sjostrand F

and Maloney JV Jr

Studies of controlledreperfusion after ischemiaXV Immediate functional

recovery after six hours of

regional ischemia by careful

control of conditions ofreperfusion and compositionof reperfusate J Thorac

Cardiovasc Surg 1986 92(3Pt 2) 621-35

2 Allen BS Current Conceptsin Pediatric Myocardial

Protection In Salerno TA and

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1718

Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

27

Ricci M (editors) MyocardialProtection 1st editionBlackwell publishing 2004207-29

3 Allen BS Pediatricmyocardial protection acardioplegic stra-tegy is the

solution Semin Thorac

Cardiovasc Surg Pediatr CardSurg Annu 2004 7 141-54

4 Bull C Cooper J and

Stark J Cardioplegicprotection of the childrsquos

heart J Thorac Cardio-vasc

Surg 1984 88(2) 287-93

5 Caputo M Dihmis WC

Bryan AJ Suleiman MS

and Angelini GD Warmblood hyperkalaemicreperfusion (hot shot)prevents myocardial substratederangement in patients

undergoing coronary arterybypass surgery Eur J

Cardiothorac Surg 199813(5) 559-64

6 Follette DM Fey K

Buckberg GD Helly JJ Jr

Steed DL Foglia RP and

Maloney JV Jr Reducingpostischemic damage by

temporary modifi-cation ofreperfusate calcium

potassium pH and

osmolarity J ThoracCardiovasc Surg 1981 82 (2)

221-38

7 Hammon JW Jr Myocardialprotection in the immatureheart Ann Thorac Surg 1995

60 (3) 839-842

8 Immer FF Stocker FP

Seiler AM Pfammatter JP

Printzen G and Carrel TP

Comparison of troponin-I and

troponin-T after pediatriccardiovascular opera-tion

Ann Thorac Surg 1998 66 (6)2073-7

9 Krause EG Pfeiffer D

Wollen-berger U and

Wollert HG Lactatemonitoring during and aftercardiopulmonary bypass an

approach implicating a peri-

operative measure for cardiacenergy metabolism In PiperHM Preusse CJ (editors)

Ischemia-reperfusion in

cardiac surgery 1st editionKluwer Academic 1993 317-33

10 Kronon MT Allen BS

Rahman S Wang T

Tayyab NA Bolling KS and

Ilbawi MN Reducingpostischemic reper-fusion

damage in neonates using a

terminal warm substrate-enriched blood cardioplegicreperfusate Ann Thorac Surg2000 70(3) 765-770

11 Modi P Suleiman MS

Reeves B Pawade A Parry

AJ Angelini GD and

Caputo M Myocardial

metabolic changes during ped-iatric cardiac surgery arando-mized study of 3cardioplegic techniques JThorac Cardiovasc Surg2004 128(1) 67-75

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1818

Comparison of cardioprotective effects Hussein Sabri et al

28

12 Nomura F Forbess JM

and Mayer EJ Effects ofHot shot on recovery afterhypothermic ischemia in

neonatal lamb heart JCardiovasc Surg (Torino)2001 42(1) 1-7

13 Teoh KH Christakis GT

Weisel RD Fremes SE

Mickle DA Romaschin AD

Harding RS Ivanov J

Madonik MM Ross IM et

al Accelerated myocardial

metabolic recovery with

terminal warm bloodcardioplegia J ThoracCardiovasc Surg 1986 91(6)

888-95

14 Toyoda Y Yamaguchi M

Yoshimura N Oka S and

Okita Y Cardioprotectiveeffects and the mechanisms of

terminal warm bloodcardioplegia in pediatriccardiac surgery J ThoracCardiovasc Surg 2003 125

(6) 1242-51

15 Wernovsky G Wypij D

Jonas RA Mayer JE Jr

Hanley FL Hickey PR

Walsh AZ Chang AC

Castaneda AR NewburgerJW et al Postoperativecourse and hemodynamicprofile after the arterial

switch operation in neo-natesand infants A comparison of

low-flow cardiopulmonarybypass and circulatory arrestCirculation 1995 92(8) 2226-

35

16 Young JN Choy IO SilvaNK Obayashi DY and

Barkan HE Antegrade cold

blood cardioplegia is not

demonstrably advan-tageousover cold crystalloidcardioplegia in surgery forcongenital heart disease J

Thorac Cardiovasc Surg1997 114(6) 1002-9

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1318

Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

23

Discussion

Low cardiac output aftersurgically induced ischemia andreperfusion continues to be a major

contributor to morbidity andmortality after pediatric cardiacsurgery and in more than 50 of

cases has been attributed toinadequate myocardial protection(Bull et al 1984 Hammon

1995)

Careful control of theconditions of reperfusion and the

composition of the reperfusate can

optimize postischemic recovery ofmyocardial function (Follette et

al 1981 Allen et al 1986)

The current study wasdesigned to evaluate the cardio-protective effect of using inter-mittent antegrade cold bloodcardioplegia versus intermittent

cold blood cardioplegia with ter-minal warm blood cardioplegia

(hot-shot) in pediatric cardiacpatients

The result of the current

study demonstrated significantdecrease in blood pressure at 5and 15 minutes interval in thecontrol group compared with the

hot-shot group after weaning ofthe cardiopulmonary bypass

Intermittent cold blood

cardioplegia with terminal warmblood cardioplegia offers favorable

effect on the clinical outcomeparameters This was demon-strated in this study as asignificant higher percentage ofspontaneous defibrillation into

sinus rhythm in hot-shot group

than control group (767 versus333 respectively)

The percentage of patientsrequiring inotropic support after

weaning from cardiopulmonarybypass was significantly higher incontrol group than hot-shot group

(80 versus 467 respectively)

By adopting the inotropic scoredescribed by Wernovsky et al

(1995) the level of inotropic

support was significantly lower inhot-shot group than control group

(44plusmn55 versus 105plusmn65 respec-

tively)

The improved clinical outcomerevealed the role of intermittent

cold blood cardioplegia withterminal warm blood cardioplegia inenhancement of myocardialprotection which was manifested asa reduction in myocardial arrhyth-

mia associated with ischemiareperfusion and a better myocardial

functionThe myocardial protective effect

of terminal warm blood cardioplegia

extended into the postoperativeperiod This was manifested as asignificant higher percentage ofpatients in control group than hot-

shot group who required inotropicsupport in the intensive care (80

versus 467 respectively) The

maximum dose of inotropic support(calculated by a modification of

inotropic score) was significantlyhigher in control group than hot-shot group (1225plusmn1032 versus754plusmn612 respectively) Theduration of inotropic support was

significantly higher in control group

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1418

Comparison of cardioprotective effects Hussein Sabri et al

24

than hot-shot group (149plusmn118versus 95plusmn72 respectively)

In the postoperative periodresults were comparable as

regards duration of mechanicalventilation and stay in theintensive care unit in addition to

comparable mortality rate

Myocardial oxygen extraction

ratio reflects balance betweenmyocardial oxygen supply anddemand Myocardial oxygenextraction ratio was similar

between the two studied groups

This similarity may reflect theaerobic metabolic state of the

myocardium provided by the coldblood cardioplegia in both groups

Lactate release from theischemic myocytes is considered asa reflection of anaerobic metabolism(Krause et al 1993)

A negative myocardial lactateextraction ratio indicates that

amount of lactate productionthrough anaerobic glycolysis washigher than the amount of lactate

consumption for aerobic energy pro-duction with continuing anaerobicmetabolism and impairment ofnormal aerobic energy production

While a positive myocardial

lactate extraction ratio indicatesthat amount of lactate production

through anaerobic glycolysis wasless than the amount of lactate

consumption for aerobic energyproduction and that myocardiumstarts to use lactate as a substratevia oxidative phosphorylation

Myocardial lactate extractionratio in control group stayednegative value all through the sixtyminutes of studied period which

indicates impairment of aerobicmyocardial metabolism during thisperiod In hot-shot group myo-cardial lactate extraction ratioremained negative value till 45min

after declamping of the aorta when

it becomes a positive value

This point is considered a turnfrom anaerobic to aerobic meta-

bolism and it resembles the equilib-

rium between lactate consumptionand production At this point themyocardium starts to use lactate as

a substrate via oxidative phosphor-rylation (Krause et al 1993)

The results of this studydemonstrate the recovery of aerobicmetabolism afforded by inter-

mittent cold blood cardioplegia withterminal warm blood cardioplegiaTroponin I is a myocyte-contractileapparatus protein released follo-

wing myocardial damage Troponin

I Level is considered sensitivemarker of myocardial injuryassociated with cardiac surgery

(Immer et al 1998)

In this study we demonstrated

a significant increase in post-operative troponin I at 4 8 hoursafter declamping of the aorta in

control group compared to hot-shotgroup (P value was lt0001) Thisreflects the beneficial effect of warmcardioplegic reperfusion on myo-cardial outcome in reducing themyocardial damage following

ischemiareperfusion injury

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1518

Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

25

In this study the composition ofterminal warm blood cardioplegiawas made to resemble the compo-sition of cold blood cardioplegia

used The point was to provide asolution with adequate potassiumconcentration to produce electro-mechanical arrest during reper-fusion This solution differs from the

conventional blood reperfusate in

presence of high potassiumconcentration (20mmolL-1) ahigher pH and a higher osmolarity

Thus cardioprotective effect ofterminal warm blood cardioplegia is

expected to be achieved byprolongation of electromechanicalarrest which reduces the energy

demands and counteracting tissueacidosis and edema therefore it

reduces the myocardial injury bypreservation and resynthesis ofhigh energy phosphates

There were small number ofclinical studies that have

examined specific myocardialprotection strategy in pediatric

population Utilizing an isolatedblood perfused neonatal heartpreparation Nomura et al

(2001) assessed the effects of

terminal warm blood cardioplegiaterminal warm oxygenated crys-talloid cardioplegia in comparisonwith conventional reperfusion(without any kind of terminal

cardioplegia) through assessmentrecovery of left ventricularfunction They demonstrated that

reperfusion with either terminalwarm blood cardioplegia or ter-

minal warm oxygenated crys-talloid cardioplegia resulted in

better recovery of myocardialfunction with slightly betterfunction in terminal warm bloodcardioplegia

In a clinically relevant intactanimal model that simulated theclinical condition of hypoxic

neonatal myocardium exposed toischemic stress Kronon et al

(2000) investigated the cardio-

protective effects of terminalwarm blood cardioplegic reper-fusion versus conventional reper-

fusion through assessment reco-

very of left ventricular systolicfunction and diastolic complianceThey showed that A warm cardio-

plegic reperfusion helps reduce

the reperfusion injury resultingin improved myocardial functionand metabolic recovery in hypoxicneonatal myocardium

Toyoda et al (2003) examined

the cardioprotective effect ofterminal warm blood cardioplegia inpediatric cardiac patients Blood

cardioplegia solution was composed

by mixing a hyperkalemic solutionwith oxygenated blood in 12dilutions with temperature 9oCThe terminal warm blood

cardioplegia had a finalconcentration of potassium 18mmolL-1 The results of Toyoda et alshowed beneficial effect of terminal

warm blood cardioplegia inreduction of myo-cardial injury Inagreement with Toyoda the

protocol of cardioplegiaadministered is almost similar asregard the concentration of pota-

ssium in terminal warm bloodcardioplegia (20mmolL-1) in 11

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1618

Comparison of cardioprotective effects Hussein Sabri et al

26

dilution (1 crystalloid 1 blood) withsimilar result in myocardial pro-tection and improvement in aerobicenergy metabolism As a marker of

myocardial necrosis the currentstudy used troponin I whichprovides comparable information astroponin T used in the study ofToyoda

The current study is inagreement with Modi et al

(2004) who compared the use of

crystalloid cardioplegia cold blood

cardioplegia and cold blood

cardioplegia with hot-shot incyanotic and acyanotic pediatricpatients undergoing surgical

correction The efficacy of the 3

techniques was assessed byexamination right ventricularbiopsy specimen before and afterreperfusion analysis of cellular

metabolites and assessment oftroponin I level Their resultdemonstrated that for cyanotic

patients blood cardioplegia withhot-shot reduced metabolic injury

compared with cold crystalloidcardioplegia They also showed

that cold blood cardioplegia wason its own better than crystalloid

but not as good as cold bloodcardioplegia with hot-shot

Young et al (1997) failed to

demonstrate statistical advantage

for blood cardioplegia over crys-talloid cardioplegia in surgery forcongenital heart The most impor-

tant aspect of the study of Younget al is that no obvious benefitcan be anticipated by use of blood

cardioplegia in congenital heartsurgery when only antegrade

hypothermia dosing technique isused The integrated cardioplegicapproach using warm cold ante-grade and retrograde technique

with substrate enrichment may bebeneficial for pediatric population

As conclusion the result of

the current study showed that theuse of cardioplegia with hot-shot

provides the criteria that mayimprove myocardial protectionand reduce myocardial injury inpediatric population

These criteria include warm

blood accelerates recovery oftemperature-dependent enzymatic

and metabolic function highpotassium concentration prolongs

electromechanical arrest to decreaseenergy demands alkaloid solutionwhich counteracts tissue acidosisand high osmolarity which coun-teracts tissue edema

References

1 Allen BS Okamoto F

Buckberg GD Bugyi H

Young H Leaf J

Beyersdorf F Sjostrand F

and Maloney JV Jr

Studies of controlledreperfusion after ischemiaXV Immediate functional

recovery after six hours of

regional ischemia by careful

control of conditions ofreperfusion and compositionof reperfusate J Thorac

Cardiovasc Surg 1986 92(3Pt 2) 621-35

2 Allen BS Current Conceptsin Pediatric Myocardial

Protection In Salerno TA and

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1718

Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

27

Ricci M (editors) MyocardialProtection 1st editionBlackwell publishing 2004207-29

3 Allen BS Pediatricmyocardial protection acardioplegic stra-tegy is the

solution Semin Thorac

Cardiovasc Surg Pediatr CardSurg Annu 2004 7 141-54

4 Bull C Cooper J and

Stark J Cardioplegicprotection of the childrsquos

heart J Thorac Cardio-vasc

Surg 1984 88(2) 287-93

5 Caputo M Dihmis WC

Bryan AJ Suleiman MS

and Angelini GD Warmblood hyperkalaemicreperfusion (hot shot)prevents myocardial substratederangement in patients

undergoing coronary arterybypass surgery Eur J

Cardiothorac Surg 199813(5) 559-64

6 Follette DM Fey K

Buckberg GD Helly JJ Jr

Steed DL Foglia RP and

Maloney JV Jr Reducingpostischemic damage by

temporary modifi-cation ofreperfusate calcium

potassium pH and

osmolarity J ThoracCardiovasc Surg 1981 82 (2)

221-38

7 Hammon JW Jr Myocardialprotection in the immatureheart Ann Thorac Surg 1995

60 (3) 839-842

8 Immer FF Stocker FP

Seiler AM Pfammatter JP

Printzen G and Carrel TP

Comparison of troponin-I and

troponin-T after pediatriccardiovascular opera-tion

Ann Thorac Surg 1998 66 (6)2073-7

9 Krause EG Pfeiffer D

Wollen-berger U and

Wollert HG Lactatemonitoring during and aftercardiopulmonary bypass an

approach implicating a peri-

operative measure for cardiacenergy metabolism In PiperHM Preusse CJ (editors)

Ischemia-reperfusion in

cardiac surgery 1st editionKluwer Academic 1993 317-33

10 Kronon MT Allen BS

Rahman S Wang T

Tayyab NA Bolling KS and

Ilbawi MN Reducingpostischemic reper-fusion

damage in neonates using a

terminal warm substrate-enriched blood cardioplegicreperfusate Ann Thorac Surg2000 70(3) 765-770

11 Modi P Suleiman MS

Reeves B Pawade A Parry

AJ Angelini GD and

Caputo M Myocardial

metabolic changes during ped-iatric cardiac surgery arando-mized study of 3cardioplegic techniques JThorac Cardiovasc Surg2004 128(1) 67-75

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1818

Comparison of cardioprotective effects Hussein Sabri et al

28

12 Nomura F Forbess JM

and Mayer EJ Effects ofHot shot on recovery afterhypothermic ischemia in

neonatal lamb heart JCardiovasc Surg (Torino)2001 42(1) 1-7

13 Teoh KH Christakis GT

Weisel RD Fremes SE

Mickle DA Romaschin AD

Harding RS Ivanov J

Madonik MM Ross IM et

al Accelerated myocardial

metabolic recovery with

terminal warm bloodcardioplegia J ThoracCardiovasc Surg 1986 91(6)

888-95

14 Toyoda Y Yamaguchi M

Yoshimura N Oka S and

Okita Y Cardioprotectiveeffects and the mechanisms of

terminal warm bloodcardioplegia in pediatriccardiac surgery J ThoracCardiovasc Surg 2003 125

(6) 1242-51

15 Wernovsky G Wypij D

Jonas RA Mayer JE Jr

Hanley FL Hickey PR

Walsh AZ Chang AC

Castaneda AR NewburgerJW et al Postoperativecourse and hemodynamicprofile after the arterial

switch operation in neo-natesand infants A comparison of

low-flow cardiopulmonarybypass and circulatory arrestCirculation 1995 92(8) 2226-

35

16 Young JN Choy IO SilvaNK Obayashi DY and

Barkan HE Antegrade cold

blood cardioplegia is not

demonstrably advan-tageousover cold crystalloidcardioplegia in surgery forcongenital heart disease J

Thorac Cardiovasc Surg1997 114(6) 1002-9

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1418

Comparison of cardioprotective effects Hussein Sabri et al

24

than hot-shot group (149plusmn118versus 95plusmn72 respectively)

In the postoperative periodresults were comparable as

regards duration of mechanicalventilation and stay in theintensive care unit in addition to

comparable mortality rate

Myocardial oxygen extraction

ratio reflects balance betweenmyocardial oxygen supply anddemand Myocardial oxygenextraction ratio was similar

between the two studied groups

This similarity may reflect theaerobic metabolic state of the

myocardium provided by the coldblood cardioplegia in both groups

Lactate release from theischemic myocytes is considered asa reflection of anaerobic metabolism(Krause et al 1993)

A negative myocardial lactateextraction ratio indicates that

amount of lactate productionthrough anaerobic glycolysis washigher than the amount of lactate

consumption for aerobic energy pro-duction with continuing anaerobicmetabolism and impairment ofnormal aerobic energy production

While a positive myocardial

lactate extraction ratio indicatesthat amount of lactate production

through anaerobic glycolysis wasless than the amount of lactate

consumption for aerobic energyproduction and that myocardiumstarts to use lactate as a substratevia oxidative phosphorylation

Myocardial lactate extractionratio in control group stayednegative value all through the sixtyminutes of studied period which

indicates impairment of aerobicmyocardial metabolism during thisperiod In hot-shot group myo-cardial lactate extraction ratioremained negative value till 45min

after declamping of the aorta when

it becomes a positive value

This point is considered a turnfrom anaerobic to aerobic meta-

bolism and it resembles the equilib-

rium between lactate consumptionand production At this point themyocardium starts to use lactate as

a substrate via oxidative phosphor-rylation (Krause et al 1993)

The results of this studydemonstrate the recovery of aerobicmetabolism afforded by inter-

mittent cold blood cardioplegia withterminal warm blood cardioplegiaTroponin I is a myocyte-contractileapparatus protein released follo-

wing myocardial damage Troponin

I Level is considered sensitivemarker of myocardial injuryassociated with cardiac surgery

(Immer et al 1998)

In this study we demonstrated

a significant increase in post-operative troponin I at 4 8 hoursafter declamping of the aorta in

control group compared to hot-shotgroup (P value was lt0001) Thisreflects the beneficial effect of warmcardioplegic reperfusion on myo-cardial outcome in reducing themyocardial damage following

ischemiareperfusion injury

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1518

Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

25

In this study the composition ofterminal warm blood cardioplegiawas made to resemble the compo-sition of cold blood cardioplegia

used The point was to provide asolution with adequate potassiumconcentration to produce electro-mechanical arrest during reper-fusion This solution differs from the

conventional blood reperfusate in

presence of high potassiumconcentration (20mmolL-1) ahigher pH and a higher osmolarity

Thus cardioprotective effect ofterminal warm blood cardioplegia is

expected to be achieved byprolongation of electromechanicalarrest which reduces the energy

demands and counteracting tissueacidosis and edema therefore it

reduces the myocardial injury bypreservation and resynthesis ofhigh energy phosphates

There were small number ofclinical studies that have

examined specific myocardialprotection strategy in pediatric

population Utilizing an isolatedblood perfused neonatal heartpreparation Nomura et al

(2001) assessed the effects of

terminal warm blood cardioplegiaterminal warm oxygenated crys-talloid cardioplegia in comparisonwith conventional reperfusion(without any kind of terminal

cardioplegia) through assessmentrecovery of left ventricularfunction They demonstrated that

reperfusion with either terminalwarm blood cardioplegia or ter-

minal warm oxygenated crys-talloid cardioplegia resulted in

better recovery of myocardialfunction with slightly betterfunction in terminal warm bloodcardioplegia

In a clinically relevant intactanimal model that simulated theclinical condition of hypoxic

neonatal myocardium exposed toischemic stress Kronon et al

(2000) investigated the cardio-

protective effects of terminalwarm blood cardioplegic reper-fusion versus conventional reper-

fusion through assessment reco-

very of left ventricular systolicfunction and diastolic complianceThey showed that A warm cardio-

plegic reperfusion helps reduce

the reperfusion injury resultingin improved myocardial functionand metabolic recovery in hypoxicneonatal myocardium

Toyoda et al (2003) examined

the cardioprotective effect ofterminal warm blood cardioplegia inpediatric cardiac patients Blood

cardioplegia solution was composed

by mixing a hyperkalemic solutionwith oxygenated blood in 12dilutions with temperature 9oCThe terminal warm blood

cardioplegia had a finalconcentration of potassium 18mmolL-1 The results of Toyoda et alshowed beneficial effect of terminal

warm blood cardioplegia inreduction of myo-cardial injury Inagreement with Toyoda the

protocol of cardioplegiaadministered is almost similar asregard the concentration of pota-

ssium in terminal warm bloodcardioplegia (20mmolL-1) in 11

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1618

Comparison of cardioprotective effects Hussein Sabri et al

26

dilution (1 crystalloid 1 blood) withsimilar result in myocardial pro-tection and improvement in aerobicenergy metabolism As a marker of

myocardial necrosis the currentstudy used troponin I whichprovides comparable information astroponin T used in the study ofToyoda

The current study is inagreement with Modi et al

(2004) who compared the use of

crystalloid cardioplegia cold blood

cardioplegia and cold blood

cardioplegia with hot-shot incyanotic and acyanotic pediatricpatients undergoing surgical

correction The efficacy of the 3

techniques was assessed byexamination right ventricularbiopsy specimen before and afterreperfusion analysis of cellular

metabolites and assessment oftroponin I level Their resultdemonstrated that for cyanotic

patients blood cardioplegia withhot-shot reduced metabolic injury

compared with cold crystalloidcardioplegia They also showed

that cold blood cardioplegia wason its own better than crystalloid

but not as good as cold bloodcardioplegia with hot-shot

Young et al (1997) failed to

demonstrate statistical advantage

for blood cardioplegia over crys-talloid cardioplegia in surgery forcongenital heart The most impor-

tant aspect of the study of Younget al is that no obvious benefitcan be anticipated by use of blood

cardioplegia in congenital heartsurgery when only antegrade

hypothermia dosing technique isused The integrated cardioplegicapproach using warm cold ante-grade and retrograde technique

with substrate enrichment may bebeneficial for pediatric population

As conclusion the result of

the current study showed that theuse of cardioplegia with hot-shot

provides the criteria that mayimprove myocardial protectionand reduce myocardial injury inpediatric population

These criteria include warm

blood accelerates recovery oftemperature-dependent enzymatic

and metabolic function highpotassium concentration prolongs

electromechanical arrest to decreaseenergy demands alkaloid solutionwhich counteracts tissue acidosisand high osmolarity which coun-teracts tissue edema

References

1 Allen BS Okamoto F

Buckberg GD Bugyi H

Young H Leaf J

Beyersdorf F Sjostrand F

and Maloney JV Jr

Studies of controlledreperfusion after ischemiaXV Immediate functional

recovery after six hours of

regional ischemia by careful

control of conditions ofreperfusion and compositionof reperfusate J Thorac

Cardiovasc Surg 1986 92(3Pt 2) 621-35

2 Allen BS Current Conceptsin Pediatric Myocardial

Protection In Salerno TA and

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1718

Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

27

Ricci M (editors) MyocardialProtection 1st editionBlackwell publishing 2004207-29

3 Allen BS Pediatricmyocardial protection acardioplegic stra-tegy is the

solution Semin Thorac

Cardiovasc Surg Pediatr CardSurg Annu 2004 7 141-54

4 Bull C Cooper J and

Stark J Cardioplegicprotection of the childrsquos

heart J Thorac Cardio-vasc

Surg 1984 88(2) 287-93

5 Caputo M Dihmis WC

Bryan AJ Suleiman MS

and Angelini GD Warmblood hyperkalaemicreperfusion (hot shot)prevents myocardial substratederangement in patients

undergoing coronary arterybypass surgery Eur J

Cardiothorac Surg 199813(5) 559-64

6 Follette DM Fey K

Buckberg GD Helly JJ Jr

Steed DL Foglia RP and

Maloney JV Jr Reducingpostischemic damage by

temporary modifi-cation ofreperfusate calcium

potassium pH and

osmolarity J ThoracCardiovasc Surg 1981 82 (2)

221-38

7 Hammon JW Jr Myocardialprotection in the immatureheart Ann Thorac Surg 1995

60 (3) 839-842

8 Immer FF Stocker FP

Seiler AM Pfammatter JP

Printzen G and Carrel TP

Comparison of troponin-I and

troponin-T after pediatriccardiovascular opera-tion

Ann Thorac Surg 1998 66 (6)2073-7

9 Krause EG Pfeiffer D

Wollen-berger U and

Wollert HG Lactatemonitoring during and aftercardiopulmonary bypass an

approach implicating a peri-

operative measure for cardiacenergy metabolism In PiperHM Preusse CJ (editors)

Ischemia-reperfusion in

cardiac surgery 1st editionKluwer Academic 1993 317-33

10 Kronon MT Allen BS

Rahman S Wang T

Tayyab NA Bolling KS and

Ilbawi MN Reducingpostischemic reper-fusion

damage in neonates using a

terminal warm substrate-enriched blood cardioplegicreperfusate Ann Thorac Surg2000 70(3) 765-770

11 Modi P Suleiman MS

Reeves B Pawade A Parry

AJ Angelini GD and

Caputo M Myocardial

metabolic changes during ped-iatric cardiac surgery arando-mized study of 3cardioplegic techniques JThorac Cardiovasc Surg2004 128(1) 67-75

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1818

Comparison of cardioprotective effects Hussein Sabri et al

28

12 Nomura F Forbess JM

and Mayer EJ Effects ofHot shot on recovery afterhypothermic ischemia in

neonatal lamb heart JCardiovasc Surg (Torino)2001 42(1) 1-7

13 Teoh KH Christakis GT

Weisel RD Fremes SE

Mickle DA Romaschin AD

Harding RS Ivanov J

Madonik MM Ross IM et

al Accelerated myocardial

metabolic recovery with

terminal warm bloodcardioplegia J ThoracCardiovasc Surg 1986 91(6)

888-95

14 Toyoda Y Yamaguchi M

Yoshimura N Oka S and

Okita Y Cardioprotectiveeffects and the mechanisms of

terminal warm bloodcardioplegia in pediatriccardiac surgery J ThoracCardiovasc Surg 2003 125

(6) 1242-51

15 Wernovsky G Wypij D

Jonas RA Mayer JE Jr

Hanley FL Hickey PR

Walsh AZ Chang AC

Castaneda AR NewburgerJW et al Postoperativecourse and hemodynamicprofile after the arterial

switch operation in neo-natesand infants A comparison of

low-flow cardiopulmonarybypass and circulatory arrestCirculation 1995 92(8) 2226-

35

16 Young JN Choy IO SilvaNK Obayashi DY and

Barkan HE Antegrade cold

blood cardioplegia is not

demonstrably advan-tageousover cold crystalloidcardioplegia in surgery forcongenital heart disease J

Thorac Cardiovasc Surg1997 114(6) 1002-9

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1518

Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

25

In this study the composition ofterminal warm blood cardioplegiawas made to resemble the compo-sition of cold blood cardioplegia

used The point was to provide asolution with adequate potassiumconcentration to produce electro-mechanical arrest during reper-fusion This solution differs from the

conventional blood reperfusate in

presence of high potassiumconcentration (20mmolL-1) ahigher pH and a higher osmolarity

Thus cardioprotective effect ofterminal warm blood cardioplegia is

expected to be achieved byprolongation of electromechanicalarrest which reduces the energy

demands and counteracting tissueacidosis and edema therefore it

reduces the myocardial injury bypreservation and resynthesis ofhigh energy phosphates

There were small number ofclinical studies that have

examined specific myocardialprotection strategy in pediatric

population Utilizing an isolatedblood perfused neonatal heartpreparation Nomura et al

(2001) assessed the effects of

terminal warm blood cardioplegiaterminal warm oxygenated crys-talloid cardioplegia in comparisonwith conventional reperfusion(without any kind of terminal

cardioplegia) through assessmentrecovery of left ventricularfunction They demonstrated that

reperfusion with either terminalwarm blood cardioplegia or ter-

minal warm oxygenated crys-talloid cardioplegia resulted in

better recovery of myocardialfunction with slightly betterfunction in terminal warm bloodcardioplegia

In a clinically relevant intactanimal model that simulated theclinical condition of hypoxic

neonatal myocardium exposed toischemic stress Kronon et al

(2000) investigated the cardio-

protective effects of terminalwarm blood cardioplegic reper-fusion versus conventional reper-

fusion through assessment reco-

very of left ventricular systolicfunction and diastolic complianceThey showed that A warm cardio-

plegic reperfusion helps reduce

the reperfusion injury resultingin improved myocardial functionand metabolic recovery in hypoxicneonatal myocardium

Toyoda et al (2003) examined

the cardioprotective effect ofterminal warm blood cardioplegia inpediatric cardiac patients Blood

cardioplegia solution was composed

by mixing a hyperkalemic solutionwith oxygenated blood in 12dilutions with temperature 9oCThe terminal warm blood

cardioplegia had a finalconcentration of potassium 18mmolL-1 The results of Toyoda et alshowed beneficial effect of terminal

warm blood cardioplegia inreduction of myo-cardial injury Inagreement with Toyoda the

protocol of cardioplegiaadministered is almost similar asregard the concentration of pota-

ssium in terminal warm bloodcardioplegia (20mmolL-1) in 11

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1618

Comparison of cardioprotective effects Hussein Sabri et al

26

dilution (1 crystalloid 1 blood) withsimilar result in myocardial pro-tection and improvement in aerobicenergy metabolism As a marker of

myocardial necrosis the currentstudy used troponin I whichprovides comparable information astroponin T used in the study ofToyoda

The current study is inagreement with Modi et al

(2004) who compared the use of

crystalloid cardioplegia cold blood

cardioplegia and cold blood

cardioplegia with hot-shot incyanotic and acyanotic pediatricpatients undergoing surgical

correction The efficacy of the 3

techniques was assessed byexamination right ventricularbiopsy specimen before and afterreperfusion analysis of cellular

metabolites and assessment oftroponin I level Their resultdemonstrated that for cyanotic

patients blood cardioplegia withhot-shot reduced metabolic injury

compared with cold crystalloidcardioplegia They also showed

that cold blood cardioplegia wason its own better than crystalloid

but not as good as cold bloodcardioplegia with hot-shot

Young et al (1997) failed to

demonstrate statistical advantage

for blood cardioplegia over crys-talloid cardioplegia in surgery forcongenital heart The most impor-

tant aspect of the study of Younget al is that no obvious benefitcan be anticipated by use of blood

cardioplegia in congenital heartsurgery when only antegrade

hypothermia dosing technique isused The integrated cardioplegicapproach using warm cold ante-grade and retrograde technique

with substrate enrichment may bebeneficial for pediatric population

As conclusion the result of

the current study showed that theuse of cardioplegia with hot-shot

provides the criteria that mayimprove myocardial protectionand reduce myocardial injury inpediatric population

These criteria include warm

blood accelerates recovery oftemperature-dependent enzymatic

and metabolic function highpotassium concentration prolongs

electromechanical arrest to decreaseenergy demands alkaloid solutionwhich counteracts tissue acidosisand high osmolarity which coun-teracts tissue edema

References

1 Allen BS Okamoto F

Buckberg GD Bugyi H

Young H Leaf J

Beyersdorf F Sjostrand F

and Maloney JV Jr

Studies of controlledreperfusion after ischemiaXV Immediate functional

recovery after six hours of

regional ischemia by careful

control of conditions ofreperfusion and compositionof reperfusate J Thorac

Cardiovasc Surg 1986 92(3Pt 2) 621-35

2 Allen BS Current Conceptsin Pediatric Myocardial

Protection In Salerno TA and

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1718

Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

27

Ricci M (editors) MyocardialProtection 1st editionBlackwell publishing 2004207-29

3 Allen BS Pediatricmyocardial protection acardioplegic stra-tegy is the

solution Semin Thorac

Cardiovasc Surg Pediatr CardSurg Annu 2004 7 141-54

4 Bull C Cooper J and

Stark J Cardioplegicprotection of the childrsquos

heart J Thorac Cardio-vasc

Surg 1984 88(2) 287-93

5 Caputo M Dihmis WC

Bryan AJ Suleiman MS

and Angelini GD Warmblood hyperkalaemicreperfusion (hot shot)prevents myocardial substratederangement in patients

undergoing coronary arterybypass surgery Eur J

Cardiothorac Surg 199813(5) 559-64

6 Follette DM Fey K

Buckberg GD Helly JJ Jr

Steed DL Foglia RP and

Maloney JV Jr Reducingpostischemic damage by

temporary modifi-cation ofreperfusate calcium

potassium pH and

osmolarity J ThoracCardiovasc Surg 1981 82 (2)

221-38

7 Hammon JW Jr Myocardialprotection in the immatureheart Ann Thorac Surg 1995

60 (3) 839-842

8 Immer FF Stocker FP

Seiler AM Pfammatter JP

Printzen G and Carrel TP

Comparison of troponin-I and

troponin-T after pediatriccardiovascular opera-tion

Ann Thorac Surg 1998 66 (6)2073-7

9 Krause EG Pfeiffer D

Wollen-berger U and

Wollert HG Lactatemonitoring during and aftercardiopulmonary bypass an

approach implicating a peri-

operative measure for cardiacenergy metabolism In PiperHM Preusse CJ (editors)

Ischemia-reperfusion in

cardiac surgery 1st editionKluwer Academic 1993 317-33

10 Kronon MT Allen BS

Rahman S Wang T

Tayyab NA Bolling KS and

Ilbawi MN Reducingpostischemic reper-fusion

damage in neonates using a

terminal warm substrate-enriched blood cardioplegicreperfusate Ann Thorac Surg2000 70(3) 765-770

11 Modi P Suleiman MS

Reeves B Pawade A Parry

AJ Angelini GD and

Caputo M Myocardial

metabolic changes during ped-iatric cardiac surgery arando-mized study of 3cardioplegic techniques JThorac Cardiovasc Surg2004 128(1) 67-75

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1818

Comparison of cardioprotective effects Hussein Sabri et al

28

12 Nomura F Forbess JM

and Mayer EJ Effects ofHot shot on recovery afterhypothermic ischemia in

neonatal lamb heart JCardiovasc Surg (Torino)2001 42(1) 1-7

13 Teoh KH Christakis GT

Weisel RD Fremes SE

Mickle DA Romaschin AD

Harding RS Ivanov J

Madonik MM Ross IM et

al Accelerated myocardial

metabolic recovery with

terminal warm bloodcardioplegia J ThoracCardiovasc Surg 1986 91(6)

888-95

14 Toyoda Y Yamaguchi M

Yoshimura N Oka S and

Okita Y Cardioprotectiveeffects and the mechanisms of

terminal warm bloodcardioplegia in pediatriccardiac surgery J ThoracCardiovasc Surg 2003 125

(6) 1242-51

15 Wernovsky G Wypij D

Jonas RA Mayer JE Jr

Hanley FL Hickey PR

Walsh AZ Chang AC

Castaneda AR NewburgerJW et al Postoperativecourse and hemodynamicprofile after the arterial

switch operation in neo-natesand infants A comparison of

low-flow cardiopulmonarybypass and circulatory arrestCirculation 1995 92(8) 2226-

35

16 Young JN Choy IO SilvaNK Obayashi DY and

Barkan HE Antegrade cold

blood cardioplegia is not

demonstrably advan-tageousover cold crystalloidcardioplegia in surgery forcongenital heart disease J

Thorac Cardiovasc Surg1997 114(6) 1002-9

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1618

Comparison of cardioprotective effects Hussein Sabri et al

26

dilution (1 crystalloid 1 blood) withsimilar result in myocardial pro-tection and improvement in aerobicenergy metabolism As a marker of

myocardial necrosis the currentstudy used troponin I whichprovides comparable information astroponin T used in the study ofToyoda

The current study is inagreement with Modi et al

(2004) who compared the use of

crystalloid cardioplegia cold blood

cardioplegia and cold blood

cardioplegia with hot-shot incyanotic and acyanotic pediatricpatients undergoing surgical

correction The efficacy of the 3

techniques was assessed byexamination right ventricularbiopsy specimen before and afterreperfusion analysis of cellular

metabolites and assessment oftroponin I level Their resultdemonstrated that for cyanotic

patients blood cardioplegia withhot-shot reduced metabolic injury

compared with cold crystalloidcardioplegia They also showed

that cold blood cardioplegia wason its own better than crystalloid

but not as good as cold bloodcardioplegia with hot-shot

Young et al (1997) failed to

demonstrate statistical advantage

for blood cardioplegia over crys-talloid cardioplegia in surgery forcongenital heart The most impor-

tant aspect of the study of Younget al is that no obvious benefitcan be anticipated by use of blood

cardioplegia in congenital heartsurgery when only antegrade

hypothermia dosing technique isused The integrated cardioplegicapproach using warm cold ante-grade and retrograde technique

with substrate enrichment may bebeneficial for pediatric population

As conclusion the result of

the current study showed that theuse of cardioplegia with hot-shot

provides the criteria that mayimprove myocardial protectionand reduce myocardial injury inpediatric population

These criteria include warm

blood accelerates recovery oftemperature-dependent enzymatic

and metabolic function highpotassium concentration prolongs

electromechanical arrest to decreaseenergy demands alkaloid solutionwhich counteracts tissue acidosisand high osmolarity which coun-teracts tissue edema

References

1 Allen BS Okamoto F

Buckberg GD Bugyi H

Young H Leaf J

Beyersdorf F Sjostrand F

and Maloney JV Jr

Studies of controlledreperfusion after ischemiaXV Immediate functional

recovery after six hours of

regional ischemia by careful

control of conditions ofreperfusion and compositionof reperfusate J Thorac

Cardiovasc Surg 1986 92(3Pt 2) 621-35

2 Allen BS Current Conceptsin Pediatric Myocardial

Protection In Salerno TA and

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1718

Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

27

Ricci M (editors) MyocardialProtection 1st editionBlackwell publishing 2004207-29

3 Allen BS Pediatricmyocardial protection acardioplegic stra-tegy is the

solution Semin Thorac

Cardiovasc Surg Pediatr CardSurg Annu 2004 7 141-54

4 Bull C Cooper J and

Stark J Cardioplegicprotection of the childrsquos

heart J Thorac Cardio-vasc

Surg 1984 88(2) 287-93

5 Caputo M Dihmis WC

Bryan AJ Suleiman MS

and Angelini GD Warmblood hyperkalaemicreperfusion (hot shot)prevents myocardial substratederangement in patients

undergoing coronary arterybypass surgery Eur J

Cardiothorac Surg 199813(5) 559-64

6 Follette DM Fey K

Buckberg GD Helly JJ Jr

Steed DL Foglia RP and

Maloney JV Jr Reducingpostischemic damage by

temporary modifi-cation ofreperfusate calcium

potassium pH and

osmolarity J ThoracCardiovasc Surg 1981 82 (2)

221-38

7 Hammon JW Jr Myocardialprotection in the immatureheart Ann Thorac Surg 1995

60 (3) 839-842

8 Immer FF Stocker FP

Seiler AM Pfammatter JP

Printzen G and Carrel TP

Comparison of troponin-I and

troponin-T after pediatriccardiovascular opera-tion

Ann Thorac Surg 1998 66 (6)2073-7

9 Krause EG Pfeiffer D

Wollen-berger U and

Wollert HG Lactatemonitoring during and aftercardiopulmonary bypass an

approach implicating a peri-

operative measure for cardiacenergy metabolism In PiperHM Preusse CJ (editors)

Ischemia-reperfusion in

cardiac surgery 1st editionKluwer Academic 1993 317-33

10 Kronon MT Allen BS

Rahman S Wang T

Tayyab NA Bolling KS and

Ilbawi MN Reducingpostischemic reper-fusion

damage in neonates using a

terminal warm substrate-enriched blood cardioplegicreperfusate Ann Thorac Surg2000 70(3) 765-770

11 Modi P Suleiman MS

Reeves B Pawade A Parry

AJ Angelini GD and

Caputo M Myocardial

metabolic changes during ped-iatric cardiac surgery arando-mized study of 3cardioplegic techniques JThorac Cardiovasc Surg2004 128(1) 67-75

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1818

Comparison of cardioprotective effects Hussein Sabri et al

28

12 Nomura F Forbess JM

and Mayer EJ Effects ofHot shot on recovery afterhypothermic ischemia in

neonatal lamb heart JCardiovasc Surg (Torino)2001 42(1) 1-7

13 Teoh KH Christakis GT

Weisel RD Fremes SE

Mickle DA Romaschin AD

Harding RS Ivanov J

Madonik MM Ross IM et

al Accelerated myocardial

metabolic recovery with

terminal warm bloodcardioplegia J ThoracCardiovasc Surg 1986 91(6)

888-95

14 Toyoda Y Yamaguchi M

Yoshimura N Oka S and

Okita Y Cardioprotectiveeffects and the mechanisms of

terminal warm bloodcardioplegia in pediatriccardiac surgery J ThoracCardiovasc Surg 2003 125

(6) 1242-51

15 Wernovsky G Wypij D

Jonas RA Mayer JE Jr

Hanley FL Hickey PR

Walsh AZ Chang AC

Castaneda AR NewburgerJW et al Postoperativecourse and hemodynamicprofile after the arterial

switch operation in neo-natesand infants A comparison of

low-flow cardiopulmonarybypass and circulatory arrestCirculation 1995 92(8) 2226-

35

16 Young JN Choy IO SilvaNK Obayashi DY and

Barkan HE Antegrade cold

blood cardioplegia is not

demonstrably advan-tageousover cold crystalloidcardioplegia in surgery forcongenital heart disease J

Thorac Cardiovasc Surg1997 114(6) 1002-9

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1718

Ain Shams Journal of Anesthesiology Vol 2-2 July 2009

27

Ricci M (editors) MyocardialProtection 1st editionBlackwell publishing 2004207-29

3 Allen BS Pediatricmyocardial protection acardioplegic stra-tegy is the

solution Semin Thorac

Cardiovasc Surg Pediatr CardSurg Annu 2004 7 141-54

4 Bull C Cooper J and

Stark J Cardioplegicprotection of the childrsquos

heart J Thorac Cardio-vasc

Surg 1984 88(2) 287-93

5 Caputo M Dihmis WC

Bryan AJ Suleiman MS

and Angelini GD Warmblood hyperkalaemicreperfusion (hot shot)prevents myocardial substratederangement in patients

undergoing coronary arterybypass surgery Eur J

Cardiothorac Surg 199813(5) 559-64

6 Follette DM Fey K

Buckberg GD Helly JJ Jr

Steed DL Foglia RP and

Maloney JV Jr Reducingpostischemic damage by

temporary modifi-cation ofreperfusate calcium

potassium pH and

osmolarity J ThoracCardiovasc Surg 1981 82 (2)

221-38

7 Hammon JW Jr Myocardialprotection in the immatureheart Ann Thorac Surg 1995

60 (3) 839-842

8 Immer FF Stocker FP

Seiler AM Pfammatter JP

Printzen G and Carrel TP

Comparison of troponin-I and

troponin-T after pediatriccardiovascular opera-tion

Ann Thorac Surg 1998 66 (6)2073-7

9 Krause EG Pfeiffer D

Wollen-berger U and

Wollert HG Lactatemonitoring during and aftercardiopulmonary bypass an

approach implicating a peri-

operative measure for cardiacenergy metabolism In PiperHM Preusse CJ (editors)

Ischemia-reperfusion in

cardiac surgery 1st editionKluwer Academic 1993 317-33

10 Kronon MT Allen BS

Rahman S Wang T

Tayyab NA Bolling KS and

Ilbawi MN Reducingpostischemic reper-fusion

damage in neonates using a

terminal warm substrate-enriched blood cardioplegicreperfusate Ann Thorac Surg2000 70(3) 765-770

11 Modi P Suleiman MS

Reeves B Pawade A Parry

AJ Angelini GD and

Caputo M Myocardial

metabolic changes during ped-iatric cardiac surgery arando-mized study of 3cardioplegic techniques JThorac Cardiovasc Surg2004 128(1) 67-75

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1818

Comparison of cardioprotective effects Hussein Sabri et al

28

12 Nomura F Forbess JM

and Mayer EJ Effects ofHot shot on recovery afterhypothermic ischemia in

neonatal lamb heart JCardiovasc Surg (Torino)2001 42(1) 1-7

13 Teoh KH Christakis GT

Weisel RD Fremes SE

Mickle DA Romaschin AD

Harding RS Ivanov J

Madonik MM Ross IM et

al Accelerated myocardial

metabolic recovery with

terminal warm bloodcardioplegia J ThoracCardiovasc Surg 1986 91(6)

888-95

14 Toyoda Y Yamaguchi M

Yoshimura N Oka S and

Okita Y Cardioprotectiveeffects and the mechanisms of

terminal warm bloodcardioplegia in pediatriccardiac surgery J ThoracCardiovasc Surg 2003 125

(6) 1242-51

15 Wernovsky G Wypij D

Jonas RA Mayer JE Jr

Hanley FL Hickey PR

Walsh AZ Chang AC

Castaneda AR NewburgerJW et al Postoperativecourse and hemodynamicprofile after the arterial

switch operation in neo-natesand infants A comparison of

low-flow cardiopulmonarybypass and circulatory arrestCirculation 1995 92(8) 2226-

35

16 Young JN Choy IO SilvaNK Obayashi DY and

Barkan HE Antegrade cold

blood cardioplegia is not

demonstrably advan-tageousover cold crystalloidcardioplegia in surgery forcongenital heart disease J

Thorac Cardiovasc Surg1997 114(6) 1002-9

7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip

httpslidepdfcomreaderfullcomparative-study-between-cardioprotective-effects-of-intermitternt-antegrade 1818

Comparison of cardioprotective effects Hussein Sabri et al

28

12 Nomura F Forbess JM

and Mayer EJ Effects ofHot shot on recovery afterhypothermic ischemia in

neonatal lamb heart JCardiovasc Surg (Torino)2001 42(1) 1-7

13 Teoh KH Christakis GT

Weisel RD Fremes SE

Mickle DA Romaschin AD

Harding RS Ivanov J

Madonik MM Ross IM et

al Accelerated myocardial

metabolic recovery with

terminal warm bloodcardioplegia J ThoracCardiovasc Surg 1986 91(6)

888-95

14 Toyoda Y Yamaguchi M

Yoshimura N Oka S and

Okita Y Cardioprotectiveeffects and the mechanisms of

terminal warm bloodcardioplegia in pediatriccardiac surgery J ThoracCardiovasc Surg 2003 125

(6) 1242-51

15 Wernovsky G Wypij D

Jonas RA Mayer JE Jr

Hanley FL Hickey PR

Walsh AZ Chang AC

Castaneda AR NewburgerJW et al Postoperativecourse and hemodynamicprofile after the arterial

switch operation in neo-natesand infants A comparison of

low-flow cardiopulmonarybypass and circulatory arrestCirculation 1995 92(8) 2226-

35

16 Young JN Choy IO SilvaNK Obayashi DY and

Barkan HE Antegrade cold

blood cardioplegia is not

demonstrably advan-tageousover cold crystalloidcardioplegia in surgery forcongenital heart disease J

Thorac Cardiovasc Surg1997 114(6) 1002-9