Immature Myocardium & Fetal Circulation

Seoul National University HospitalDepartment of Thoracic & Cardiovascular Surgery

Fetal Circulation

• Is adapted to a special situation

• Depends on placenta for O2/nutrients

• Is rarely overloaded, but if overloaded little reserve

Fetal Circulation

Parallel circulation (combined output)

Communications between R and L heart

Pulmonary circulation is redundant

Flow Pathway and Distribution

• % indicates the proportion of combined output

Oxygen Saturation of Fetal Flow

Normal Fetal Circulation

• Major fetal flow patterns and blood hemoglobin oxygen saturation

Normal Fetal Circulation

• Values for percentages of cardiac output returning to and leaving the heart in normal fetal lamb

Normal Fetal Circulation

• Values for vascular pressure in normal fetal lamb

Normal Fetal Blood Gas

Transitional Circulation and CHD

• As circulation separates, TGA can not supply enough oxygen to the body

• Obstructed pathway in either side hardly tolerateright : PA or critical PS in any CHDleft : Aortic atresia or critical AS, IAA, COA mitral atresia + small PFO; obstructed TAPVR

Transitional Circulation

• Dramatic changes in circulation at the moment of birth and onwards : Air breadth - lung expansion - Rp ↓ -Qp ↑ - LA pressure ↑ - PFO ↓P O2 ↑ - ductus arteriosus and venosus ↓ Obliteration of placental circulation - Rs ↑ -IVC pressure ↓ - PFO ↓

Congenital Heart Disease in Fetus

• Often silent : TGA : has little effectHLHS : RV is slightly overloadedPA + IVS : no effect at all

• When CHD causes volume overload, heart fails and hydrops ensues

Neonatal Circulation and CHD

Neonatal circulation Potential of increased RpPotential of atrial communicationCompliance of two ventricles is nearly equal

CHD and neonatal circulationVSD, PDA : usually not symptomaticASD : usually not symptomatic

Neonatal Circulatory Physiology

1. Decreased compliance of fetal & neonatal right

& left ventricle

2. Decreased capacity for peripheral vasodilation

3. Decreased capacity for response to volume load

due to diminished preload reservoir

Characteristics of Immature Myocardium1. Greater tolerance to hypoxia & normothermic ischemia

in experimental study 1) greater capacity for anaerobic glycolysis 2) greater buffering capacity 3) decreased ATP flux secondary to lower levels of 5-

nucleotidase2. Less tolerant to ischemia based on the duration of ischemia

at the onset of contracture or intracellular accumulation of sodium and calcium, but recovery of pump function was not assessed by several reports.

3. Compromised secondary to cyanosis, volume or pressure overload with associated ventricular hypertrophy & subendocardial ischemia in clinical setting

Normal Neonatal Myocardium

Characteristics of normal myocardium• Myocardial structure Myocytes are smaller cells with single nuclei than adult and less contractile materials(30%) than adult(60%), more water, less collagen, more noncontractile protein. Small volume of mitochondria, rudimentary sarcoplasmic reticulum, fewer myofibrils, absence of T-tubules, organization of immature muscle cells in random• Function Velocity of shortening is less. Less compliant myocardium due to increased amount of noncontractile cellular element in immature myocardium

Normal Neonatal Myocardium

• Response to hypoxia Increased ability to tolerate periods of anoxia due to increased glyc

ogen storage and glycolytic acitivity• Response to ischemia Increased resistance to ischemia , but first 3-8 days of life Early onset of irreversibly injured myocardium than mature myo

cardium. More reperfusion injury, but rapid recovery without irreversible i

njury than mature myocardium • Decreased clear ability of lactate production and with stress cause

d by underlying cardiac disease, which causes high morbidity & mortality.

Structure of Neonatal Myocardium

1. Stiffer due to more water, less collagen, more contractile protein 2. Smaller cells with single nuclei, poorly developed intercalated disks, greater mitotic activity, fewer mature mitochondria, and fewer myofibrils 3. Greater storage of glycogen, enhanced rate of anaerobic glycolytic ATP production 4. Calcium homeostasis is different & more dependent on external calcium

Metabolism of Neonatal Myocardium

• Preference for glucose & glycogen over free fatty acid as energy substrates and greater concentration of glycogen in the heart • Enhanced anaerobic glycolytic ATP production capacity tha

t may represent adaptation to relative O2 deprivation during fatal condition

• Significant difference in calcium metabolism (1) Amount of calcium within cardiac cell of neonate is significantly less than that of adult. (2) Decreased ability of immature sarcoplasmic reticulum to accumulate calcium ---- the strength of contraction can be increased in neonate by increasing in extracellular calcium

Neonatal Myocardial Management

Trend of management In 1990

Equal split in the preference for crystalloid vs. blood cardioplegic solutions

In 1995 Trend toward the use of blood based solutions, with only

20% using crystalloid solutions

Neonatal Cardiac Surgery

Potential for damage duing surgery1. Preischemic stage Hypothermia

2. Ischemic stageCalcium contentMagnesiumSingle vs. multidose

3. Postischemic stage

Myocardial Protection vs. Injury

• The surgical treatment of complex congenital heart

defects in the neonate requires controlled conditions

with unimpaired exposure in a bloodless, immobile

operative field.

• The cost one pays to obtain such exposure, however,

is a period of ischemic insults to myocardium.

Effect of Hypothermia

The term, cooling contracture, rapid cooling contra

cture refers to as marked increase in resting in resp

onse to sudden decrease in temperature.

(activation of myofilaments by the release of calciu

m from intracellular stores)

Damage at Ischemic Stage1. Calcium content

o Optimal calcium concentration(?)o Calcium paradox in acalcemic solutionso PH, Na, duration of ischemia, effects(?)

-> Reduction in the ionized level of this cation in the cardioplegic solution results in better myocardial recovery

2. Magnesiumo Magnesium help maintain a negative resting membrane potential and

competitively inhibits sarcolemmal calcium influx o Superior functional recovery with solution containing magnesium in

blood perfused neonatal rabbit model o Optimal concentration is 16 mmol/l citrate calcium level temperature

3. Single-dose vs. multidose o No advantage with multiple administration

o More evident detrimental effects at infusion temperatures below 20oC and with increasing frequency of administration

Damage at Postischemic Stage After early reperfusion, the postischemic myocardial functi

onal alternation may ensue Intervention aimed at the reduction of reperfusion-mediat

ed injury1. substrate enhancement & ionic modification2. free radical scavenging3. leucocyte depletion4. reduction in perfusion pressure and temperature

Protocols for Neonatal Myocardial Protection (I)

Preischemic phaseA. Moderate hypothermic (25~28

oC) continuous CP bypass,

with intermittent periods of low flow (50ml/kg/min)B. Ionized calcium level in the range of 0.5~0.6 mmol/l * fresh frozen plasma (citrate)C. Gas flows are adjusted to maintain PCO2 level at

40~45 mmHg during cooling phase

Protocols for Neonatal Myocardial Protection (II)

Ischemic phaseA. 2:1 blood : crystalloid formulation (Hct 5%)

B. Alkalotic cardioplegic solutions may not be a as effective in the neonatal heart

C. Initial infusion is at or above room temperature bu

t is cooled to 10oC

Protocols for Neonatal Myocardial Protection (III)

Postischemic phaseA. Bypass flow rate is reduced to 50% & temperature

20~25oC for several minutes.

B. Ionized level of calcium are not normalized until

myocardial activity has returned.