Thallium-201 Redistribution Transient Myocardial...

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Time Course of Thallium-201 Redistribution After Transient Myocardial Ischemia GEORGE A. BELLER, M.D., DENNY D. WATSON, PH.D., PETER ACKELL, B.A., AND GERALD M. POHOST, M.D. SUMMARY The mechanism and time course of thallium-201 (201T1) redistribution after transient myocar- dial ischemia was investigated in 27 anesthetized dogs given 1.5 mCi of 201Tl intravenously 10 minutes after occlusion of the left anterior descending coronary artery. Coronary reperfusion (RP) was accomplished 10 minutes after 2`TI administration. Transmural myocardial biopsies were obtained in situ from normal (N) and ischemic (IS) regions during occlusion and 5 minutes (four dogs), 20 minutes (eight dogs), 90 minutes (six dogs), 4 hours (five dogs) and 6 hours (four dogs) after RP. There was a twofold rise in 201T1 activity (counts/10 min/mg) in the IS region after only 5 minutes of reflow with as yet no detectable change in 201T1 concentration in the N zone. In dogs undergoing 90 minutes of RP, 201T1 activity was 700 i 150 (SEM) in the IS zone during occlusion and markedly increased (p < 0.001) to 3200 ± 100 at 90 minutes of reflow. During this period 20'TI activity in the N region decreased only slightly, from 7000 ± 800 to 6000 ± 450 (NS). In dogs that underwent 6 hours of RP, 20'TI activity in the IS zone increased from 1700 ± 500 during occlusion to 3300 ± 200 (p < 0.001) after RP. In this group, 20'T1 activity in the N zone significantly decreased, from 6400 ± 1200 to 3900 ± 400 over the 6 hours of reflow, reflecting the magnitude of thallium washout after ischemia. This near- equalization of 201TI activity between N and IS zones was already apparent by 4 hours of RP. These data indicate that 201Tl redistribution after transient myocardial ischemia is related to both delayed accumulation of 203T1 into ischemic myocardial segments and to a more rapid washout of the radionuclide from normal segments. Qualitatively, the serial changes in myocardial 201T1 activity in ischemic and normal myocar- dium before and after flow restoration in this study, and the time course of thallium redistribution, are similar to the serial scintigraphic changes in patients who receive thallium during exercise stress or spontaneous rest angina. DEFECTS in thallium-201 (201T1) uptake appear in myocardial scintigrams in patients during exercise stress,1-7 during pain accompanying spontaneous angina8 9 and in the presence of acute10 or prior myocardial infarction.3 The initial myocardial dis- tribution of i.v. 201T1 is dependent on regional blood flow and the myocardial extraction fraction for T.3 11 Originally, 201T1 was thought to remain fixed in myocardial cells for several hours after initial uptake and that subsequently there was little change in dis- tribution. This assumption was based upon the obser- vation that the half-time for net myocardial Tl clearance after intravenous injections was found to be approximately 7 hours.'2 More recently, however, in anesthetized dogs, early TI defects appeared to fill in with 20'Tl activity after 2 hours of reperfusion after the radionuclide was administered during transient left anterior descending coronary artery (LAD) occlu- sion.3 Clinical studies have demonstrated that this redistribution of Tl is observed on delayed images after exercise in patients with stress-induced myocar- dial perfusion defects.3 7 In the presence of myocar- From the Cardiology and Nuclear Medicine Divisions, Univer- sity of Virginia School of Medicine, Charlottesville, Virginia, and the Cardiac Unit, Massachusetts General Hospital, Boston, Massa- chusetts. Supported in part by USPHS grants HL 21751 and HL 176665, and grant-in-aid 76-942 from the American Heart Association. Address for correspondence: George A. Beller, M.D., Cardiology Division, Department of Internal Medicine, Box 158, Charlottes- ville, Virginia 22908. Received April 2, 1979; revision accepted October 8, 1979. Circulation 61, No. 4, 1980. dial infarction or scar, initial defects on myocardial scintigrams persist on delayed images and no signifi- cant redistribution is evident. From these preliminary observations, it appeared that serial imaging after a single dose of 201Tl might be useful in differentiating transient ischemia and/or underperfusion from myocardial infarction or scar. The purpose of this investigation was to determine both the mechanism and time course of TI redistribu- tion after transient myocardial ischemia in an animal model in which absolute TI concentration in ischemic and nonischemic regions could be serially measured with an in vivo biopsy technique. In prior studies of the kinetics of TI uptake and redistribution during acute ischemia, only relative TI activity, expressed as percent normal activity, was measured. Little infor- mation is available about what causes "filling in" of defects on delayed images. Equalization of activity between ischemic and normal myocardial zones could result from delayed accumulation of 20'Tl in the previously ischemic regions, more rapid washout of 201T1 from normal myocardium or a combination of both mechanisms. Methods Canine Experimental Ischemic Model The canine model used in these experiments has been described in detail.3 In these experiments, tran- sient ischemia was produced in 127 open-chest dogs. The dogs were anesthetized with i.v. pentobarbital (30 mg/kg) and ventilated with a Harvard respirator. By using a mixture of room air and 40% oxygen, the arterial Po2 in all dogs was maintained between 791 by guest on May 26, 2018 http://circ.ahajournals.org/ Downloaded from

Transcript of Thallium-201 Redistribution Transient Myocardial...

Time Course of Thallium-201 RedistributionAfter Transient Myocardial Ischemia

GEORGE A. BELLER, M.D., DENNY D. WATSON, PH.D., PETER ACKELL, B.A.,AND GERALD M. POHOST, M.D.

SUMMARY The mechanism and time course of thallium-201 (201T1) redistribution after transient myocar-dial ischemia was investigated in 27 anesthetized dogs given 1.5 mCi of 201Tl intravenously 10 minutes afterocclusion of the left anterior descending coronary artery. Coronary reperfusion (RP) was accomplished 10minutes after 2`TI administration. Transmural myocardial biopsies were obtained in situ from normal (N) andischemic (IS) regions during occlusion and 5 minutes (four dogs), 20 minutes (eight dogs), 90 minutes (sixdogs), 4 hours (five dogs) and 6 hours (four dogs) after RP. There was a twofold rise in 201T1 activity (counts/10min/mg) in the IS region after only 5 minutes of reflow with as yet no detectable change in 201T1 concentrationin the N zone. In dogs undergoing 90 minutes of RP, 201T1 activity was 700 i 150 (SEM) in the IS zone duringocclusion and markedly increased (p < 0.001) to 3200 ± 100 at 90 minutes of reflow. During this period 20'TIactivity in the N region decreased only slightly, from 7000 ± 800 to 6000 ± 450 (NS). In dogs that underwent6 hours of RP, 20'TI activity in the IS zone increased from 1700 ± 500 during occlusion to 3300 ± 200(p < 0.001) after RP. In this group, 20'T1 activity in the N zone significantly decreased, from 6400 ± 1200 to3900 ± 400 over the 6 hours of reflow, reflecting the magnitude of thallium washout after ischemia. This near-equalization of 201TI activity between N and IS zones was already apparent by 4 hours of RP.

These data indicate that 201Tl redistribution after transient myocardial ischemia is related to both delayedaccumulation of 203T1 into ischemic myocardial segments and to a more rapid washout of the radionuclide fromnormal segments. Qualitatively, the serial changes in myocardial 201T1 activity in ischemic and normal myocar-dium before and after flow restoration in this study, and the time course of thallium redistribution, are similarto the serial scintigraphic changes in patients who receive thallium during exercise stress or spontaneous restangina.

DEFECTS in thallium-201 (201T1) uptake appear inmyocardial scintigrams in patients during exercisestress,1-7 during pain accompanying spontaneousangina8 9 and in the presence of acute10 or priormyocardial infarction.3 The initial myocardial dis-tribution of i.v. 201T1 is dependent on regional bloodflow and the myocardial extraction fraction for T.3 11

Originally, 201T1 was thought to remain fixed inmyocardial cells for several hours after initial uptakeand that subsequently there was little change in dis-tribution. This assumption was based upon the obser-vation that the half-time for net myocardial Tlclearance after intravenous injections was found to beapproximately 7 hours.'2 More recently, however, inanesthetized dogs, early TI defects appeared to fill inwith 20'Tl activity after 2 hours of reperfusion after theradionuclide was administered during transient leftanterior descending coronary artery (LAD) occlu-sion.3

Clinical studies have demonstrated that thisredistribution of Tl is observed on delayed imagesafter exercise in patients with stress-induced myocar-dial perfusion defects.3 7 In the presence of myocar-

From the Cardiology and Nuclear Medicine Divisions, Univer-sity of Virginia School of Medicine, Charlottesville, Virginia, andthe Cardiac Unit, Massachusetts General Hospital, Boston, Massa-chusetts.

Supported in part by USPHS grants HL 21751 and HL 176665,and grant-in-aid 76-942 from the American Heart Association.Address for correspondence: George A. Beller, M.D., Cardiology

Division, Department of Internal Medicine, Box 158, Charlottes-ville, Virginia 22908.

Received April 2, 1979; revision accepted October 8, 1979.Circulation 61, No. 4, 1980.

dial infarction or scar, initial defects on myocardialscintigrams persist on delayed images and no signifi-cant redistribution is evident. From these preliminaryobservations, it appeared that serial imaging after asingle dose of 201Tl might be useful in differentiatingtransient ischemia and/or underperfusion frommyocardial infarction or scar.The purpose of this investigation was to determine

both the mechanism and time course of TI redistribu-tion after transient myocardial ischemia in an animalmodel in which absolute TI concentration in ischemicand nonischemic regions could be serially measuredwith an in vivo biopsy technique. In prior studies ofthe kinetics of TI uptake and redistribution duringacute ischemia, only relative TI activity, expressed aspercent normal activity, was measured. Little infor-mation is available about what causes "filling in" ofdefects on delayed images. Equalization of activitybetween ischemic and normal myocardial zones couldresult from delayed accumulation of 20'Tl in thepreviously ischemic regions, more rapid washout of201T1 from normal myocardium or a combination ofboth mechanisms.

Methods

Canine Experimental Ischemic Model

The canine model used in these experiments hasbeen described in detail.3 In these experiments, tran-sient ischemia was produced in 127 open-chest dogs.The dogs were anesthetized with i.v. pentobarbital (30mg/kg) and ventilated with a Harvard respirator. Byusing a mixture of room air and 40% oxygen, thearterial Po2 in all dogs was maintained between

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Occlusion LAD in 27 Dogs

10 min

1.5mC* 201 TI Iv

10 min

Myocardial Biopsy andCoronary Reperfusion

5 min (n=4)20 min (n=8)90 min (n=6)4 hrs (n=5)6 hrs (n=4)

Myocardial Biopsy

Myocardial201 TI Activity byGamma Well Counting

FIGURE 1. Experimental protocol. Duplicate biopsies ofischemic and normal regions were obtained before and aftercoronary reperfusion. LAD = left anterior descending cor-

onary artery.

80-120 mm Hg. Arterial blood pressure was con-tinuously monitored after a catheter was inserted intothe central aorta via a cutdown on one of the femoralarteries. Lead 2 of the ECG was continuouslyrecorded.The experimental protocol is summarized in figure

1. After a left thoracotomy, the mid-left anteriordescending coronary artery (LAD) was dissected freeof the epicardial surface and occluded by a snareplaced around the vessel. After 10 minutes of LADocclusion, 1.5 mCi of 201T1 chloride were injected in-travenously. Ten minutes after 201T1 injection,duplicate transmural myocardial specimens were ob-tained from the biopsy drill (24.0 X 2.0 mm) from thecenter of the regions of myocardium perfused by theoccluded vessel and from normal myocardial regionsperfused by the left circumflex coronary artery. Thedrill bit was attached to a Sears Rotary-Tool (model758-25161) and samples were obtained at a rotaryspeed of 2400 rpm. In no dog in this study werearrhythmias produced by this technique, and the

arterial blood pressure remained stable during thebiopsy procedure. Bleeding from the biopsy site wascontained by gentle pressure over the site of entry.Within several minutes, bleeding from the area usuallyceased.

In all 27 dogs, coronary reperfusion was institutedby release of the occluding snare, 10 minutes after Tladministration (20 minutes after occlusion). The dura-tion of reperfusion was 5 minutes in four dogs, 20minutes in eight dogs, 90 minutes in six dogs, 4 hoursin five dogs, and 6 hours in four dogs.

Serial venous blood specimens were withdrawn dur-ing both occlusion and reperfusion periods in all dogsto determine blood clearance curves for theradionuclide. At the end of the reperfusion periods, asecond set of duplicate transmural biopsies were ob-tained from ischemic and normal myocardium. Aswith the postocclusion specimens, all myocardialspecimens were blotted dry on filter paper, weighedand counted in a multichannel gamma well scintilla-tion counter (Packard Instrument Company, Chicago,Illinois). Thallium activity was expressed as counts/10min/mg of wet weight. The myocardial samplesweighed 10-25 mg. Blood 201T1 activity was expressedas counts/10 min/mg of blood.

Statistical AnalysisAll data are presented as mean ± SEM. The

significance of differences was assessed by the paired ttest using a two-tailed distribution.

Results

Figures 2-5 show the changes in myocardial 201T1activity in ischemic and normal zones in the dogs un-dergoing 5 minutes, 20 minutes, 90 minutes or 6 hoursof coronary reperfusion after a 20-minute period ofLAD occlusion. Thallium was injected intravenously10 minutes before reperfusion. Values for the 4-hourreperfusion group were comparable to the vailuesobserved in the 6-hour group and are only shown infigure 6, which normalizes and summarizes the ex-perimental data for all 27 dogs.The change in myocardial TI concentration from

the end of the 20-minute occlusion period to 5 minutesof reperfusion for four dogs are shown in figure 2.There was almost a twofold rise in Tl activity in theischemic zone over this brief period of reflow. Therewas no detectable change in TI concentration in thenormal region at 5 minutes of reflow. In the eight dogsthat underwent 20 minutes of reperfusion (fig. 3), Tlactivity was 500 ± 200 (SEM) counts/ 10 min/mg in theischemic zone during occlusion and markedly in-creased (p < 0.001) to 1750 ± 450 counts/ 10 min/mgat 20 minutes of reflow. As was observed in the 5-minute group, there still was no detectable change inTI concentration in the normal zone at this time.Thallium activity was 4200 ± 800 and 4150 ± 700counts/10 min/mg in the normal zone at 20 minutesof occlusion and 20 minutes of reperfusion, respec-tively.

Qualitatively similar changes appeared in the dogs

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Mean ± SEN=4

* Ischemic1 Normal

FIGURE 2. Myocardial thallium-201 (20177)activity (mean ± SEM), expressed as counts/10 min/mg in four dogs after 20 minutes ofleft anterior descending coronary arteryocclusion and after 5 minutes of reflow.

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occluded for 20 minutes and reperfused for 90 minutes(fig. 4). Thallium concentration in the ischemic zonerose from 700 ± 150 counts/10 min/mg to3200 ± 100 from occlusion to 90 minutes of reflow(p < 0.001). This change was significantly greaterthan that observed in the 5- or 20-minute groups.Thallium concentration in the normal zone fell from

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7000 ± 800 to 6000 ± 450 counts/10 min/mg by 90minutes of reperfusion (NS).

In contrast to these early reflow periods, changes inmyocardial TI concentration in ischemic and non-ischemic myocardium in the 6-hour reperfused dogsdemonstrated a significantly greater decrease in Tl ac-tivity in the normal zone. In this group (fig. 5), near-

Mean ± SEN=8* IschemicO Normal

FIGURE 3. Myocardial thallium-201 (201TI)activity (mean ± SEM) in ischemic and nor-mal regions after 20 minutes of left anteriordescending coronary artery occlusion andafter 20 minutes of reflow.

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FIGURE 4. Myocardial thallium-201 (201T1)activity in ischemic and normal regionsafter 20 minutes of left anterior descendingcoronary artery occlusion and after 90minutes of reflow.

li l30 40 50 60 70 80 90 100 110 120

ow

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equalization of activity between ischemic and normalzones can be observed and is related to a significantearly accumulation of TI into the ischemic region andthe more rapid washout of Tl from normal myocar-dium. Myocardial TI activity increased from1700 ± 500 counts/10 min/mg after 20 minutes of

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ATReflow201 Tl

Occlusion Time (min)FIGURE 5. Myocardial thallium-201 (201T1) activity in is-chemic and normal regions after 20 minutes of left anteriordescending coronary artery occlusion and after 360 minutesof reflow.

occlusion to 3300 ± 200 counts/10 min/mg at 6 hoursof reperfusion (fig. 5). During this period, 201T1 activityin the normal region fell from 6400 ± 1200 to3900 ± 400 counts/10 min/mg.

Figure 6 combines the data from all five groups ofdogs. Values for each group were normalized by ex-pressing T1 concentration in ischemic regions as per-cent of initial normal values. Thallium concentrationsfor normal myocardium before reflow was designatedas 100%. Changes in TI concentrations in both normaland ischemic regions are represented as percentages ofthis initial normal activity. Normalizing values for allgroups of dogs in this manner allows for a better ap-preciation of the pattern and time course of Tlredistribution after transient myocardial ischemia.The half-time for net Tl washout from normalmyocardium for these groups of dogs was 7.2 hours, avalue similar to that reported previously.12 From 5-90minutes of reperfusion the rate of Tl accumulation inthe ischemic zone is rapid, with little washout in nor-mal regions (fig. 6). However, from 90 minutes to 6hours of reperfusion, the difference in TI activitybetween ischemic and normal zones narrows moregradually and is predominantly due to a more rapidwashout of TI from the normal zone compared withthe ischemic zone. By 3 hours, the difference in TI con-centration between ischemic zones and normal zonesis sufficiently decreased so that an in vivo scintigramobtained at this time and including the effects ofbackground and imperfect sampling of the ischemiczone would probably have shown disappearance of theinitial myocardial defect.

Figure 7 is a typical blood clearance curve for 201T1after i.v. administration in a representative dog fromthis study. There is a rapid decline in blood TI activitysoon after tracer injection, and a plateau is ap-

Oli 10

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_T ~~~~~~~~~~~~~~moonI bea g ~~~~~~~~~~~~~N=27

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Z 100

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FIGURE 6. Serial determination of myocardial thallium-201 (201TI) activity, expressed as percent of initial(before reflow) normal 201Tl activity in allfive groups ofdogs occludedfor 20 minutes and reperfusedfor 5,20, 90, 240 and 360 minutes. The initial value of 201Tl activity in the ischemic region was obtained beforereflow and represents the mean ± SEMfor all 27 dogs. Near-equalization of 201T1 concentration in normaland previously ischemic myocardial regions appears by 4 hours.

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minutes after injection. Redistribution of between ischemic and normal zones appears. In thisover a 6-hour postischemic period in this study, there was more than a fivefold decrease in TIed in the presence of sustained low blood concentration 20 minutes after coronary occlusion intions. ischemic myocardium. This decrease in initial TI con-

Discussion centration reflects the relative diminution in bloodflow as demonstrated by an early study3 that demon-

a demonstrate that when 201T1 is ad- strated a linear correlation between myocardial TIintravenously during coronary artery concentration and relative regional myocardial bloodlarge gradient in TI concentration flow as determined by the microsphere technique. In

the present study, when blood flow was restored tonormal after 20 tninutes of transient LAD occlusion,TI redistribution occurred so that over a period oftime, normalization of TI activity appeared in thepreviously ischemic zone. From 5-90 minutes ofreperfusion, the rate of Tl accumulation in ischenlicmyocardium was relatively rapid, whereas the TI con-centration in the normally perfused regions decreasedquite slowly. By 90 minutes after flow restoration, theTI concentration in the normal myocardium decreasedby 10%; however, there was more than a 300% in-crease in activity in the previously ischemic zone. Dur-ing the period from 2-4 hours, the concentration of TIin the ischemic zone was approaching that of the nor-mal myocardium at a slower rate, and by 4-6 hoursthe TI concentrations in both previously ischemic andnormal zones were comparable.

( )- i 23 4 5 6 7 8 These data are consistent with a compartmentalmodel to explain the redistribution phenomena.'3 In

Time Hrs. this model, it is recognized that immediately after i.v.lood clearance curve for intravenously in- injection, TI is distributed throughout the body rough-i-201 (0` Tl) in a representative dog reperfused ly in proportion to the distribution of cardiac output,Fre hours. A plateau in blood 201T1 concentra- with approximately 4% of the TI accumulated by the'by 20 minutes after radionuclide administra- myocardium and more than 90% by extracardiac

organs. After the initial distribution of TI, continual

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exchange of TI occurs between the extracardiac organsand the myocardium. Myocardial regions that wereinitially deprived of TI but have restored perfusion andthat still have viable cell membrane function will con-tinue to extract Tl, which is being recirculated throughthe blood from the extracardiac compartment so as toeventually normalize the intracellular TI concentra-tion. After enough time has passed, all of the viablemyocardial cells will reach a stable value of in-tracellular TI concentration. This delayed myocardialconcentration thus reflects an exchange equilibriumthat will be the same for all viable myocardial cellsthat later have equal perfusion regardless of the un-equal initial concentration that reflected the unequalperfusion at the time of injection. The data from thisstudy suggest that significant redistribution would oc-cur within 30 minutes to 1 hour after injection and thatnormalization of activity would be observed 2-4 hoursafter injection.The findings of this present study are comparable to

those described by Schwartz et al., who showed thatredistribution of TI occurred in significant proportionbeginning 5 minutes after reflow in pigs that un-derwent temporary occlusion of the circumflex cor-onary artery.`4 In this latter study, however, coronaryflow was reestablished after only 4 minutes of occlu-sion. At this time, our blood clearance data indicatedthat the blood concentration of TI after injection wasstill high, so that much of the TI accumulation in thetransiently ischemic region occurred during the initialdistribution phase. In the present study, TI redistribu-tion occurred even though 10 minutes elapsed betweenTl administration and reperfusion at a time whenblood levels of the tracer were markedly lower (fig. 7).Additionally, in the study by Schwartz et al., changesin TI activity were only assessed up to 105 minutes ofreperfusion, and longer periods were not examined;therefore, the time course of redistribution could notbe accurately assessed.The clinical relevance of these experimental data

pertain to the redistribution of Ti after theradionuclide is administered intravenously during ex-ercise stress3 7 or during an episode of variant anginapectoris.8 9 In these clinical situations, there isheterogeneous perfusion of the left ventricularmyocardium when Tl is injected. In the instance of ex-ercise stress, flow is significantly enhanced to regionsof myocardium supplied by nonobstructed coronaryvessels, but areas perfused by arteries with significantstenoses demonstrate little or no increase in flow.Since myocardial TI uptake is proportional to flow,more Tl will be delivered to normal than to underper-fused regions, causing a relative defect. After cessationof exercise and restoration of the resting flow state, therelative defect may normalize within 2-4 hours afterexercise and redistribution is considered to have oc-curred, presumably by the mechanism describedabove. In the presence of prior infarction and scar, in-itial defects remain persistent in the postexerciseperiod.

In conclusion, this study demonstrates that when

sion in dogs, near-equalization of activity between nor-mal and ischemic zones occurs by 4 hours, althoughsignificant redistribution occurs by 20 minutes afterflow restoration. The mechanism of TI redistributionin this model is related both to delayed accumulationof TI into previously ischemic myocardial segmentsand to more rapid net Tl washout from normalsegments. In this model, the differing rates of ac-cumulation and/or washout are observed at a timewhen perfusion has been restored to its normal level,and are therefore presumed to be caused by thedifferent concentration gradients between previouslyischemic and normal zones that favor net influx or netefflux. The changes in regional myocardial TI activityin ischemic myocardium before and after flow restora-tion in this canine study, and the time course of TIredistribution, are similar to the serial scintigraphicchanges observed in patients with coronary artery dis-ease who undergo exercise stress or spontaneous restangina.

AcknowledgmentThe authors cite the superb technical assistance of Jack Irving

and Beth Essington in these studies.

References1. Bailey IK, Griffith LSC, Rouleau J, Strauss HW, Pitt B:

Thallium-201 myocardial perfusion imaging at rest and duringexercise. Comparative sensitivity to electrocardiography in cor-onary artery disease. Circulation 55: 80, 1977

2. Ritchie JL, Trobaugh GB, Hamilton GW, Gould KL,Narahara KA, Murray JA, Williams DL: Myocardial imagingwith thallium-201 at rest and during exercise: comparison withcoronary arteriography and resting and stress electrocar-diography. Circulation 56: 66, 1977

3. Pohost GM, Zir LM, Moore RH, McKusick KA, Guiney TE,Beller GA: Differentiation of transiently ischemic from in-farcted myocardium by serial imaging after a single dose ofthallium-201. Circulation 55: 294, 1977

4. Carrillo AP, Marks DS, Pickard SD, Khaja F, Goldstein S:Correlation of exercise 201thalliurn myocardial scan with cor-onary arteriograms and the maximal exercise test. Chest 73:321, 1978

5. Botvinick EH, Taradash MR, Shames DM, Parmley WW:Thallium-201 myocardial perfusion scintigraphy for the clinicalclarification of normal, abnormal and equivocal electrocar-diographic stress test. Am J Cardiol 41: 43, 1978

6. Ritchie JL, Zaret BL, Strauss HW, Pitt B, Berman DS,Schelbert HR, Ashburn WL, Berger HJ, Hamilton J: Myocar-dial imaging with thallium-201: a multicenter study in patientswith angina pectoris or acute myocardial infarction. Am J Car-diol 42: 345, 1978

7. Blood DK, McCarthy DM, Sciacca RR, Cannon PJ: Com-parison of single-dose and double-dose thallium-201 myocar-dial perfusion scintigraphy for the detection of coronary arterydisease and prior myocardial infarction. Circulation 58: 777,1978

8. Maseri A, Parodi 0, Severi S, Pesola A: Transient transmuralreduction of myocardial blood flow, demonstrated by thallium-201 scintigraphy, as a cause of variant angina. Circulation 54:280, 1976

9. McLaughlin PR, Doherty PW, Martin RP, Goris ML,Harrison DC: Myocardial imaging in a patient with reproduci-ble angina. Am J Cardiol 39: 126, 1977

10. Wackers FJTh, Sokole EB, Samson G, Schoot JB, VD, Lie KI,Leim KL, Wellens HJJ: Value and limitations of thallium-201scintigraphy in the acute phase of myocardial infarction. NEngl J Med 295: 1, 1976

11. Strauss HW, Harrison K, Langan JK, Lebowitz E, Pitt B:201T1 is administered during transient coronary occlu-

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to regional myocardial perfusion. Circulation 51: 641, 197512. Bradley-Moore PR, Lebowitz E, Greene MW, Atkins HL, An-

sari AN: Thallium-201 for medical use. II. Biologic behavior. JNucl Med 16: 156, 1975

13. Beller GA, Watson DD, Pohost GM: Kinetics of thallium dis-tribution and redistribution: clinical applications in sequential

myocardial imaging. In Cardiovascular Nuclear Medicine, 2nded, edited by Strauss HW, Pitt B. St. Louis, CV Mosby, 1979,pp 225-242

14. Schwartz JS, Ponto R, Carlyle P, Forstrom L, Cohn JN: Earlyredistribution of thallium-201 after temporary ischemia. Cir-culation 57: 332, 1978

Linear Relationship Between the Distributionof Thallium-201 and Blood Flow in Ischemic

and Nonischemic Myocardium During ExerciseANTON P. NIELSEN, M.D., KENNETH G. MORRIS, M.D., ROBERT MURDOCK, B.S.,

FREDERICK P. BRUNO, M.S., AND FREDERICK R. COBB, M.D.

SUMMARY The purpose of this study was to compare the myocardial distribution of thallium-201 andregional myocardial blood flow during ischemia and the physiologic stress of exercise. Studies were carried outin six dogs with chronically implanted catheters in the atrium and aorta and a snare on the circumflex coronary

artery distal to the first marginal branch. Regional myocardial blood flow was measured during quiet, restingconditions using 7-10 , of radioisotope-labeled microspheres. Each dog was then exercised on a treadmill atspeeds of 5-9 mph at a 50 incline. After 1 minute of exercise the circumflex coronary artery was occluded andthallium-201 and a second label of microspheres were injected. Exercise was continued for 5 minutes. The dogswere then sacrificed and the left ventricle was sectioned into approximately 80 1-2-g samples to comparethallium-201 activity and regional myocardial blood flow.The maximum increase in blood flow ranged from 3.3-7.2 times resting control values. Each dog had

myocardial samples in which blood flow was markedly reduced, to less than 0.10 ml/min/g. In each dog therewas a close linear relationship between thallium-201 distribution and direct measurements of regional myocar-dial blood flow. Linear regression analyses demonstrated a correlation coefficient of 0.98 or greater in eachdog. These data indicate that during the physiologic stress of exercise, the myocardial distribution of thalliumactivity is linearly related to regional myocardial blood flow in both the ischemic and nonischemic regions.

THALLIUM-201 is the most frequently usedradioisotope tracer to evaluate regional myocardialperfusion. Although thallium-201 scintigrams of theheart during rest and exercise stress testing have beenuseful for diagnosing coronary artery disease, anumber of patients with significant coronary arterydisease by cardiac catheterization do not demonstratedeficits on thallium scintigrams. -3 This apparent in-sensitivity to significant disease may be related toseveral variables, including limitation of available im-aging equipment,4 inability to resolve small perfusiondeficits,4 early redistribution of radioisotope,5 variableinterpretation of signlficant anatomic disease, variablerelationship between anatomic disease and clinical

From the Departments of Medicine, Division of Cardiology andRadiology, Duke University Medical Center and the Veterans Ad-ministration Medical Center, Durham, North Carolina.

Supported in part by USPHS grant HL 18537, SCOR grant HL17670 from the NHLBI, and the Medical Research Service of theVeterans Administration Medical Center.

Address for correspondence: Frederick R. Cobb, M.D., Divisionof Cardiology, Veterans Administration Medical Center, 508Fulton Street, Durham, North Carolina 27705.

Received May 29, 1979; revision accepted October 10, 1979.Circulation 61, No. 4, 1980.

manifestation of ischemia,6 and inconsistent re-lationship between thallium-201 distribution and myo-cardial blood flow.6, 8' Although experimental studieshave demonstrated a close linear relationship betweenthallium-20 1 activity and direct measurements ofregional myocardial blood flow after acute coronaryartery occlusion,4 7 certain studies have indicated thatthe thallium-20 1 distribution may not be linearlyrelated to myocardial perfusion when blood flow is in-creased above control values.6 8, 9 The relationshipbetween the myocardial distribution of thallium-201and regional myocardial perfusion during ischemiaand the physiologic stress of exercise has not beenreported.

In this study we compared the myocardial distribu-tion of thallium-201 and regional myocardial bloodflow during exercise and ischemia. Directmeasurements of regional myocardial blood flow weremade using the radioisotope-labeled microspheretechnique.10, X1

MethodsSix mongrel dogs were trained to run on a

motorized treadmill using positive reinforcement tech-niques. Each dog was anesthetized with thiamylal

797

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G A Beller, D D Watson, P Ackell and G M PohostTime course of thallium-201 redistribution after transient myocardial ischemia.

Print ISSN: 0009-7322. Online ISSN: 1524-4539 Copyright © 1980 American Heart Association, Inc. All rights reserved.

is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231Circulation doi: 10.1161/01.CIR.61.4.791

1980;61:791-797Circulation. 

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