Min Of Coronary Occlusion Research Articles

Coronary vascular reserve in the greyhound with left ventricular hypertrophy.

The effects of physiological left ventricular hypertrophy on coronary reactivity and reserve were examined by comparing greyhounds with their remarkable myocardial hypertrophy with mongrel dogs (left ventricular body weight ratios 7.7(0.1) and 4.4(0.1) g X kg-1 respectively). Peak reactive hyperaemia and flow debt repayment after 15 s coronary occlusions were virtually identical in both groups at baseline heart rates and paced atrial rates up to 270 beats X min-1. Furthermore, the changes in myocardial blood flow and its transmural distribution after release of a 45 s coronary occlusion both at baseline heart rate and during atrial pacing at 210 beats X min-1 were similar in both greyhounds and mongrel dogs. Collateral flow during a 1 min coronary occlusion in conscious animals and myocardial flows and distribution during treadmill exercise were also similar. To determine minimal coronary vascular resistance intracoronary adenosine (400-600 micrograms X min-1) was infused to dilate maximally the coronary vasculature without having appreciable systemic effects. In both groups of dogs adenosine increased coronary flow six to seven fold. Coronary vascular resistance per gram of left ventricle decreased equally, and the minimal resistance was 2200(147) kPa X litre-1 X min X g (RU X g-1) in greyhounds and 2360(453) RU X g-1 in mongrels, thus indicating similar maximal vascularity in each gram of the hypertrophied and mongrel left ventricles. Because of the larger greyhound heart, the minimal coronary vascular resistance for the entire left ventricle (11.7(0.7)RU) was 50% of that in mongrel dogs (24.1(0.7)RU). Thus all forms of left ventricular hypertrophy cannot be assumed to have similar effects on the coronary vasculature. Whereas the pathological hypertrophy associated with renovascular hypertension and aortic banding is accompanied by decreased coronary vascularity, the myocardial hypertrophy of the greyhound is accompanied by increased total vascularity and preserved coronary reserve.

Influence of dipyridamole on infarct size and on cardiac nucleoside content following coronary occlusion in the dog.

The effects of 3 different doses (0.02, 0.1, 0.5 mg/kg/h) of dipyridamole on myocardial infarct size were evaluated in pentobarbital anesthetized open-chest dogs following sequential coronary occlusion of two medium sized coronary arteries in the same heart. The first coronary occlusion produced a control infarct, the other a test infarct under the influence of the drug. Dipyridamole infusion was started 10 min before the second occlusion at a rate of 0.02 (group A, n = 9), 0.1 (group B, n = 10) or 0.5 (group C, n = 9) mg/kg/h respectively and continued to the end of reperfusion (90 min). Biopsy samples were obtained at the end of each occlusion period and at the end of the second reflow period. Infarct size was determined using post mortem angiography and pNBT staining. Control and treated infarct sizes, expressed as a percentage of the perfusion area, were 21.9 +/- 5.4% vs. 25.2 +/- 7.7% in group A (n = 9), 21.8 +/- 7.3% vs. 18.3 +/- 5.2% in group B (n = 9), and 22.3 +/- 7.7% vs. 16.2 +/- 4.8% in group C (n = 8). There were no significant differences between control and treated infarct sizes in the 3 groups. After 90 min coronary occlusion tissue adenosine contents in the ischemic myocardium were significantly higher (42 +/- 7 nmol/gww in group C and 40 +/- 5 nmol/gww in group B) than those in the nonischemic myocardium, and dipyridamole enhanced these levels (395 +/- 6 nmol/gww in group C: p less than 0.01, 55 +/- 10 nmol/gww in group B). Dipyridamole did not affect the tissue inosine levels in the ischemic myocardium after 90 min coronary occlusion. ATP and creatine phosphate levels were not affected by dipyridamole during ischemia or during reflow. The accumulated adenosine was not phosphorylated to AMP and on to ATP upon reperfusion.

Cardiac response to submaximal exercise in dogs susceptible to sudden cardiac death.

The hemodynamic response to submaximal exercise was investigated in 38 mongrel dogs with healed anterior wall myocardial infarctions. The dogs were chronically instrumented to measure heart rate (HR), left ventricular pressure (LVP), LVP rate of change, and coronary blood flow. A 2 min coronary occlusion was initiated during the last minute of an exercise stress test and continued for 1 min after cessation of exercise. Nineteen dogs had ventricular fibrillation (susceptible) while 19 animals did not (resistant) during this test. The cardiac response to submaximal exercise was markedly different between the two groups. The susceptible dogs exhibited a significantly higher HR and left ventricular end-diastolic pressure (LVEDP) but a significantly lower left ventricular systolic pressure (LVSP) in response to exercise than did the resistant animals. (For example, response to 6.4 kph at 8% grade; HR, susceptible 201.4 +/- 5.1 beats/min vs. resistant 176.2 +/- 5.6 beats/min; LVEDP, susceptible 19.4 +/- 1.1 mmHg vs. resistant 12.3 +/- 1.7 mmHg; LVSP, susceptible 136.9 +/- 7.9 mmHg vs. resistant 154.6 +/- 9.8 mmHg.) beta-Adrenergic receptor blockade with propranolol reduced the difference noted in the HR response but exacerbated the LVP differences (response to 6.4 kph at 8% grade; HR, susceptible 163.4 +/- 4.7 mmHg vs. resistant 150.3 +/- 6.4 mmHg; LVEDP susceptible 28.4 +/- 2.1 mmHg vs. resistant 19.6 +/- 3.0 mmHg; LVSP, susceptible 122.2 +/- 8.1 mmHg vs. resistant 142.8 +/- 10.7 mmHg). These data indicate that the animals particularly vulnerable to ventricular fibrillation also exhibit a greater degree of left ventricular dysfunction and an increased sympathetic efferent activity.

Effects of unilateral stellate ganglion stimulation and ablation on electrophysiologic changes induced by acute myocardial ischemia in dogs.

We recorded direct-current extracellular electrograms simultaneously from 60 left ventricular epicardial sites in 38 alpha-chloralose-anesthetized dogs during repeated, 5 min coronary arterial occlusions. In each dog recordings made during control occlusions were compared with those made in occlusions after, or during, the following interventions on the sympathetic nervous system: left stellate ganglion stimulation, left stellectomy, right stellectomy, and clamping the abdominal aorta with intact sympathetic nerves to induce a rise of blood pressure equal to that present during left stellate stimulation. Heart rate was kept constant. Measurements included determination of TQ segment potentials and times of local activation. After 2 min of ischemia, the degree of TQ segment depression was increased by left stellate ganglion stimulation and was decreased by both left stellectomy and clamping the aorta. Also, the area showing negative TQ potentials, indicating decreased resting membrane potentials, was enlarged by both left stellate stimulation and right stellectomy and reduced by left stellectomy. No differences were found in the results of experiments in which the left anterior descending coronary artery was occluded and those in which the circumflex branch was occluded. Left stellate stimulation significantly improved conduction within the ischemic zone. No evidence was found to suggest that the arrhythmogenic effects of left stellate stimulation and of right stellectomy, confirmed in the present study, resulted from an increased likelihood for reentry in the subepicardium of the ischemic zone.

Effect of α-adrenergic blockade on arrhythmias induced by acute myocardial ischemia and reperfusion in the dog

Studies in cats suggest α-adrenergic contributions to arrhythmias during myocardial ischemia and reperfusion. The validity of this concept in other species, however, remains uncertain. Thus, 106 chloralose-anesthetized open-chest dogs undergoing a 25 min coronary artery occlusion followed by reperfusion received saline (n=52), prazosin (1 mg/kg, n=26), phentolamine (5 mg/kg, n=18), or phentolamine (same dose)+propranolol (1 mg/kg, n=10). Alpha-blockade was, confirmed by α-agonist dose-response studies. In phentolamine-treated dogs, arterial pressure and heart rate were kept constant to prevent exacerbation of ischemia. Control and treated groups were comparable with respect to variables known to affect arrhythmias, such as size of occluded and reperfused vascular beds, coronary collateral flow, severity of ischemia estimated from intramyocardial CO2 tension, and peak reactive hyperemia. During coronary occlusion, the number of single premature ventricular complexes was reduced by phentolamine (P<0.01), but not by prazosin or phentolamine+propranolol; no treatment affected the total number of couplets, ventricular tachycardia episodes and ventricular ectopic complexes, or the incidence of ventricular tachycardia and ventricular fibrillation. During coronary reperfusion, arrhythmias did not differ in control and treated groups. Thus, selective α1-(prazosin), nonselective α1- and α2-(phentolamine), and combined α- and β-blockade (phentolamine+propranolol) failed to attenuate complex arrhythmias induced by acute myocardial ischemia and reperfusion. Alpha-adrenergic mechanisms appear unimportant in the genesis of these arrhythmias in the canine model. Studies in cats suggest α-adrenergic contributions to arrhythmias during myocardial ischemia and reperfusion. The validity of this concept in other species, however, remains uncertain. Thus, 106 chloralose-anesthetized open-chest dogs undergoing a 25 min coronary artery occlusion followed by reperfusion received saline (n=52), prazosin (1 mg/kg, n=26), phentolamine (5 mg/kg, n=18), or phentolamine (same dose)+propranolol (1 mg/kg, n=10). Alpha-blockade was, confirmed by α-agonist dose-response studies. In phentolamine-treated dogs, arterial pressure and heart rate were kept constant to prevent exacerbation of ischemia. Control and treated groups were comparable with respect to variables known to affect arrhythmias, such as size of occluded and reperfused vascular beds, coronary collateral flow, severity of ischemia estimated from intramyocardial CO2 tension, and peak reactive hyperemia. During coronary occlusion, the number of single premature ventricular complexes was reduced by phentolamine (P<0.01), but not by prazosin or phentolamine+propranolol; no treatment affected the total number of couplets, ventricular tachycardia episodes and ventricular ectopic complexes, or the incidence of ventricular tachycardia and ventricular fibrillation. During coronary reperfusion, arrhythmias did not differ in control and treated groups. Thus, selective α1-(prazosin), nonselective α1- and α2-(phentolamine), and combined α- and β-blockade (phentolamine+propranolol) failed to attenuate complex arrhythmias induced by acute myocardial ischemia and reperfusion. Alpha-adrenergic mechanisms appear unimportant in the genesis of these arrhythmias in the canine model.

Cardiac Emission Computed Tomography

Possible effects of regional wall motion abnormalities on apparent regional myocardial tracer concentrations on emission tomographic images were evaluated in six open chest dogs. Each dog was studied twice: In Run 1, 13N ammonia and microspheres were injected during a 6 min coronary occlusion, and serial images acquired by positron emission tomography during occlusion and reperfusion. In Run 2, 1 h later, 13N ammonia and microspheres were reinjected at control, and serial images recorded at control, during a repeat 6 min coronary occlusion, and after reperfusion. Segmental function was monitored with ultrasonic crystals, and 13N tissue concentrations determined in vivo from the tomographic images and postmortem by well counting. In Run 1, fractional shortening in ischemic segments fell by 89 +/- 16% SD from control. The ischemic versus control segment ratio for 13N activity concentrations averaged 0.29 +/- 0.08 and for microspheres 0.20 +/- 0.15. In Run 2 the ischemic versus control segment ratio was at control 0.77 +/- 0.12 for 13N tissue activity and 0.85 +/- 0.07 for microspheres. Fractional shortening fell during occlusion by 131 +/- 29% from control, returned to control early, and fell again by 11 +/- 16% late during reperfusion. These changes were paralleled by changes in apparent regional 13N tissue concentrations of the prelabeled myocardium. Compared with control, they were 37 +/- 9% lower during occlusion and rose to 94 +/- 20% early and to 89 +/- 16% at control late during reperfusion. In vitro determined tissue concentration ratios of ischemic to control myocardium were similar for 13N and microsphere activity (0.83 and 0.85), which ruled out loss of 13N ammonia from tissue during occlusion or reperfusion. Our results indicate that regional wall motion abnormalities cause artifactual segmental defects in tracer concentrations on emission tomographic images of the heart, which must be considered for qualitative and quantitative analysis of regional tracer tissue concentrations.

Effect of α-adrenergic blockade on arrhythmias induced byacute myocardial ischemia and reperfusion in the dog

Studies in cats suggest alpha-adrenergic contributions to arrhythmias during myocardial ischemia and reperfusion. The validity of this concept in other species, however, remains uncertain. Thus, 106 chloralose-anesthetized open-chest dogs undergoing a 25 min coronary artery occlusion followed by reperfusion received saline (n = 52), prazosin (1 mg/kg, n = 26), phentolamine (5 mg/kg, n = 18), or phentolamine (same dose) + propranolol (1 mg/kg, n = 10). Alpha-blockade was confirmed by alpha-agonist dose-response studies. In phentolamine-treated dogs, arterial pressure and heart rate were kept constant to prevent exacerbation of ischemia. Control and treated groups were comparable with respect to variables known to affect arrhythmias, such as size of occluded and reperfused vascular beds, coronary collateral flow, severity of ischemia estimated from intramyocardial CO2 tension, and peak reactive hyperemia. During coronary occlusion, the number of single premature ventricular complexes was reduced by phentolamine (P less than 0.01), but not by prazosin or phentolamine + propranolol; no treatment affected the total number of couplets, ventricular tachycardia episodes and ventricular ectopic complexes, or the incidence of ventricular tachycardia and ventricular fibrillation. During coronary reperfusion, arrhythmias did not differ in control and treated groups. Thus, selective alpha 1-(prazosin), nonselective alpha 1- and alpha 2-(phentolamine), and combined alpha- and beta-blockade (phentolamine + propranolol) failed to attenuate complex arrhythmias induced by acute myocardial ischemia and reperfusion. Alpha-adrenergic mechanisms appear unimportant in the genesis of these arrhythmias in the canine model.

The effects of daily exercise on susceptibility to sudden cardiac death.

The purpose of this study was to investigate the effects of daily exercise on susceptibility to sudden cardiac death. A 2 min coronary occlusion was initiated during the last minute of an exercise stress test and continued for 1 min after cessation of exercise in chronically instrumented dogs with a healed anterior wall myocardial infarction. Thirteen dogs developed ventricular fibrillation (VF; susceptible), while five did not (resistant). Before the exercise plus ischemia test, the baroreflex was evaluated with a bolus injection of phenylephrine (10 micrograms/kg). The changes in heart rate caused by a 30 mm Hg increase in systolic arterial pressure as well as the slopes of either heart rate or RR interval plotted against systolic arterial pressure were significantly lower in dogs that developed VR (resistant, -49.6 +/- 7.8; susceptible, -15.3 +/- 6.4 beats/min; p less than .001). Four resistant and eight susceptible animals were then placed on a 6 week daily exercise program, while eight susceptible dogs had an equal period of rest. At the end of the 6 week period the exercise plus ischemia test was repeated; no susceptible animal that performed daily exercise developed VF, and all but one of the rested animals did. Daily exercise improved baroreflex control of heart rate in the susceptible group but not in the resistant group. Rest did not alter baroreflex function (change in heart rate after 30 mm Hg increase in systolic arterial pressure: after 6 weeks of exercise, resistant -43.3 +/- 18.9 beats/min, susceptible -60.8 +/- 16.6 beats/min; after 6 weeks of rest, susceptible 27.4 +/- 11.0 beats/min). We conclude that daily exercise prevents VF induced by acute myocardial ischemia in a subpopulation of dogs that were previously identified as susceptible to sudden cardiac death. Exercise also altered the autonomic control of the heart, possibly decreasing sympathetic and/or increasing parasympathetic tone.(ABSTRACT TRUNCATED AT 250 WORDS)

Ischaemia-induced changes in canine cardiac sarcoplasmic reticulum.

Effects of myocardial ischaemia on sarcoplasmic reticulum (SR) of dog hearts were investigated. Regional ischaemia was produced by occlusion of the left circumflex artery, and a microsomal fraction enriched in vesicles of SR was isolated from subendocardium (Endo) and subepicardium (Epi) of control and ischaemic areas of the heart. No significant changes occurred in ischaemic Epi. A loss of in vitro activities (ie calcium transport and ATPase) was found for SR from ischaemic Endo which paralleled the changes in the histology of the tissue. At 5 min of coronary occlusion, Ca2+ binding and Ca2+-ATPase activities of SR from ischaemic Endo were normal. A decrease in the activities of SR was first evident at 15 min after the occlusion, decreased further at about 30 min and remained at that level at 60 min of ischaemia. The maximal rate of Ca2+ uptake did not parallel the Ca2+-binding and Ca2+-ATPase activities. The degree of cAMP-dependent phosphorylation by endogenous and exogenous protein kinase was not different between SR from control and ischaemic areas. A participatory role of SR in the ischaemic impairment of left ventricular systolic and diastolic performance is discussed.

Effects of dazoxiben on arrhythmias and ventricular fibrillation induced by coronary artery occlusion and reperfusion in anaesthetised greyhounds.

1 The effects of the thromboxane synthetase inhibitor dazoxiben (UK 37248) on haemodynamics, blood gases, thromboxane and prostacyclin release and on arrhythmias were examined in anaesthetised greyhounds subject to acute coronary artery occlusion and reperfusion. 2 Ten minutes after the administration of UK 37248 2 mg/kg intravenously, the plasma concentration of thromboxane B2 in the coronary sinus was significantly reduced whereas the 6-keto-prostaglandin F1 alpha concentration was increased. 3 UK 37248 did not significantly alter the number of arrhythmias or the incidence of ventricular fibrillation resulting from coronary artery occlusion. There was evidence, however, that in some drug-treated animals there may have been incomplete inhibition of thromboxane synthesis during coronary artery occlusion. 4 A further dose of 1 mg/kg UK 37248 was administered intravenously 5 min before the release of the 40 min coronary artery occlusion. Seven out of eight control dogs died in ventricular fibrillation following reperfusion whereas only one out of eight drug-treated animals fibrillated. 5 This latter result suggests that thromboxane may be an important factor in reperfusion induced ventricular fibrillation and that dazoxiben may be a useful drug in clinically related situations.

Evidence that thromboxane contributes to ventricular fibrillation induced by reperfusion of the ischaemic myocardium

In many victims of sudden cardiac death, resulting from ventricular fibrillation, there is no post-mortem evidence of coronary thrombosis [ 7] and it is thought that spasm of the coronary arteries or reversal of such spasm may be the cause of the ventricular fibrillation. When coronary vasospasm is reversed, either spontaneously or by other means, arrhythmias are frequently observed when perfusion of the formerly ischaemic area of the myocardium is restored. These “reperfusion arrhythmias” are particularly severe and frequently fatal since they often progress to ventricular fibrillation. They also appear to be resistant to standard antiarrhythmic therapy [ 5] suggesting that their aetiology may vary from that of arrhythmias observed during myocardial ischaemia. We have reported previously [ 3] that thromboxane A 2, a potent vasoconstrictor which promotes platelet aggregation, is released during acute myocardial ischaemia and that this release is related to the occurrence of early cardiac arrhythmias. In the present study we have extended our experiments in anaesthetized greyhounds to investigate whether thromboxane plays a role in the reperfusion arrhythmias that occur following the release of a 40 min coronary artery occlusion. Dazoxiben (UK-37, 248), a selective thromboxane synthetase inhibitor [ 6], markedly increased survival following coronary artery reperfusion suggesting that thromboxane is an important contributory factor in post-reperfusion ventricular fibrillation.

Depressed contractile function in reperfused canine myocardium: metabolism and response to pharmacological agents.

Regional myocardial function was measured with miniature ultrasonic crystals before, during, and after 10 min of coronary occlusion in anaesthetised open-chest dogs. In normal myocardium, intracoronary isoprenaline (0.1 micrograms . min-1) increased contraction velocity during the first third of systole (early systolic velocity) from 13.8 +/- 2.5 to 19.4 +/- 3.9 mm . s-1 . cm-1, (P < 0.01), and blood flow (microspheres) from 0.55 +/- 0.04 to 0.80 +/- 0.12 cm3 . min-1 . g-1 (P < 0.05); lactate extraction was unchanged. Coronary occlusion induced dyskinesia with a fall in early systolic velocity to -10.0 +/- 2.4 mm . s . -1 . cm-1 (P < 0.01). Abrupt reperfusion after 10 min of ischaemia permitted recovery towards normal, but regional function then deteriorated over 15 min. After a second infusion of isoprenaline, early systolic velocity increased from 0.8 +/- 2.2 to 14.2 +/- 2.5 mm . s-1 . cm-1 (P < 0.01), blood flow 0.44 +/- 0.03 to 0.73 +/- 0.14 cm3 . min-1 . g-1 (P < 0.01) and oxygen consumption 50 +/- 5 to 58 +/- 5 mm3 . min-1 . g-1 (P < 0.05). Lactate extraction was unchanged. In a further series of experiments, administration of nitroglycerin and methoxamine accelerated recovery from dyskinesia induced by coronary occlusion, but did not modify late deterioration during reperfusion. Similarly, neither propranolol nor hypertonic mannitol were found to modify reperfusion damage. Four agents which affect calcium ion movement were studied. Verapamil and isoprenaline, drugs which respectively diminish and enhance calcium slow current, had no effect on reperfusion damage. By contrast, ruthenium red, a non-specific calcium inhibitor reduced deterioration and calcium ionophore (A23187; Lilly) increased it. muDepressed function in reperfused myocardium is not the result of residual ischaemia per se, gut is consistent with calcium overload during the period of reperfusion.

Rapid activation of the sympathetic nervous system following coronary artery occlusion: relationship to infarct size, site, and haemodynamic impact.

In order to define the temporal and quantitative relationship between the plasma concentrations of catecholamines and the extent and location of myocardial infarction, conscious dogs underwent left anterior descending or circumflex coronary occlusion with continuous haemodynamic monitoring. Plasma noradrenaline and adrenaline concentrations were measured by the serial isotope derivative method and infarction size by the creatine kinase depletion method. Rapid increases in plasma catecholamines were seen within 1 min of coronary occlusion. Within the first hour profound elevations of plasma adrenaline (10 fold) and noradrenaline (3 fold) occurred, with peak adrenaline and noradrenaline levels correlated to infarction size determined 24 h later in anterior (r =0.71; r =0.83) and posterior (r =0.89, r =0.78) infarctions. Cardiac output and mean systemic arterial blood pressure were inversely related to adrenaline (r =0.88, r =0.73) and noradrenaline (r =0.94, r =0.73) and deterioration in haemodynamics was always noted simultaneously with or preceding increases in plasma catecholamine concentrations. There were no significant differences in plasma catecholamines dependent on location of infarction. Thus, coronary occlusion in the conscious dog results in immediate haemodynamic deterioration and activation of the sympathetic nervous system, with a strong correlation between the two suggesting that activation of the sympathetic nervous system by haemodynamic reflexes may be of importance in the conscious canine model. The degree of autonomic activation within the first hour after occlusion appears to be related to the ultimate size of infarction, possibly because of the relationship between impairment of ventricular performance and infarct size.

Ischemic-induced alterations in cardiac sensitivity to digitalis

Intravenous infusion of acetylstrophanthidin to 6 dogs, after a 60 min left anterior descending coronary artery occlusion, was associated with a 43.0 ± 10.5% decrease in the dose of digitalis needed to produce ventricular arrhythmias as compared to the pre-ischemic dose (97.5 ± 8.0 μg/kg). Reperfusion of the ischemic region for 2 h after a 90 min occlusion resulted in a 54.4 ± 6.7% decrease in the arrhythmogenic dose. Direct intracoronary infusions of digitalis into the ischemic region, after a 90 min coronary occlusion followed by 2 h of reperfusion, was associated with a 47.7 ± 6.4% decrease in the dose of digitalis needed to produce arrhythmias. The pre-ischemic (control) arrhythmogenic dose of digitalis via the intracoronary infusion method was 1.5 ± 0.3 μg/kg (ean ± S.E.M. of 7 dogs). Sodium pump activity, estimated from the ouabain-sensitive 86Rb uptake in sodium-loaded loaded ventricular slices, was significantly higher in slices obtained from the ischemic regions (6.84 ± 0.30 nmoles 86Rb/mg dry wt. (ean ± S.E.M.), than from the non-schemic regions (3.43 ± 0.64 nmoles 86 Rb/mg dry wt.) . Sensitivity of the sodium pump activity to the inhibitory effect of ouabain was also increased in the ischemic regions as indicated by a shift in the log dose-response curve to the left. Thus, it appears that there is an increase in myocardial sensitivity to the toxic efect of digitalis after temporary ischemia and it appears to be related to an increase in the sensitivity of the Na +,K +-ATPase or sodium pump to the inhibitory effect of digitalis.

Depression of regional blood flow and wall thickening after brief coronary occlusions.

The effects of a 15-min coronary occlusion and subsequent reperfusion were investigated in conscious dogs previously instrumented for measurement of left ventricular pressure, dP/dt, regional wall thickening, electrograms, and myocardial blood flow. Coronary occlussion reduced overall left ventricular function only slightly but eliminated systolic wall thickening in the ischemic zone and reduced regional myocardial blood flow in the ischemic zone from 1.04 +/- 0.04 to 0.27 +/- 0.02 ml/min per g and the endo/epi flow ratio from 1.23 +/- 0.04 to 0.44 +/- 0.04, while S-T segment elevation increased from 1.1 +/- 0.3 to 8.2 +/- 0.9 mV. After release of the occlusion, S-T segment elevation disappeared within 1 min while reactive hyperemia in the previously occluded artery and a transient increase in cardiac diastolic wall thickness occurred and then subsided by 15 min. In contrast, systolic wall thickening and the endo/epi flow ratio remained significantly depressed for more than 3 h. Thus reperfusion after a 15 minute coronary occlusion results in a prolonged period of reduced regional myocardial blood flow, particularly in the endocardial layers, which correlates with the prolonged depression of regional myocardial shortening and wall thickening.

Decreased reactive hyperemia after coronary perfusion with nonoxygenated solution.

To gain more knowledge about the factors involved in reactive hyperemia in the coronary vessels, we performed comparative studies on the reactive hyperemia occurring after coronary occlusion and after coronary perfusion with nonoxygenated Tyrode solution. The peak coronary reactive hyperemic flow following 3 min of coronary perfusion with nonoxygenated Tyrode solution increased to only 142 +/- 16% of the control in contrast to 455 +/- 75% following 3 min of coronary occlusion alone. Myocardial oxygen uptake during reactive hyperemia was also much smaller after perfusion with Tyrode solution. First, the evidence suggests that the decreased reactive hyperemia after coronary perfusion with the nonoxygenated Tyrode solution is due to "washout" of the vasodilatory metabolites from the myocardium. Second, it suggests that there is a smaller "energy debt" during perfusion with Tyrode solution, so that deterioration of myocardial function due to oxygen deficiency is less severe than in coronary occlusion alone.

Loss of regional ventricular postextrasystolic potentiation after coronary occlusion in dogs.

Postextrasystolic potentiation following coronary artery occlusion was studied serially using pairs of ultrasonic crystals to measure regional myocardial function in control, marginally ischemic, and ischemic segments of the left ventricle in dogs. Prior to coronary occlusion (CO), percent shortening in control (normal) segments increased by an average of 51.4 +/- 4.6% in the beat after a premature ventricular contraction (post-PVC beat), and this response changed little after coronary occlusion. During the 1st min after CO, in ischemic segments, systolic expansion developed but was replaced by active shortening in post-PVC beats; however, after 3 min of CO (average) and thereafter, there was no net positive shortening in post-PVC beats. In marginally ischemic segments early after CO, hypokinesia developed, but there was marked augmentation of percent shortening (208.6 +/- 32.6%) which persisted in post-PVC beats even after 2 h. It is concluded that loss of postextrasystolic potentiation occurs rapidly in ischemic regions after CO and is not indicative of irreversible damage; partially ischemic regions retain this mechanism for prolonged periods.

Rapid assessment of ventricular fibrillation thresholds during experimental infarction in the canine heart.

Sophisticated instrumentation is described which allows the rapid estimation of vulnerability of the ventricle to multiple responses and fibrillation with the classical technique described by Wiggers and Wegria. It seems particularly pertinent to the assessment of the significance of "R on T" type of ventricular extrasystoles in myocardial infarction. The thresholds to tachyarrhythmia were decreased by about 64% within 10 min of coronary occlusion and persisted at that level for 60-90 min, suggesting the usefulness of this model in assessing anti-fibrillatory drug regimes during the early evolutionary stage of myocardial infarction.

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<b>332</b> <h3><b>Objectives</b></h3> The catecholamine analogue tracers C-11 HED and radioiodine labeled MIBG are available for sympathetic nerve activity assessment with PET (HED) and SPECT (MIBG). We compared these tracers utilizing a rat model of myocardial infarction and a dual-autoradiographic technique. <h3><b>Methods</b></h3> Thoracotomy, followed by 20 min coronary occlusion and reperfusion was performed in 6 male Wistar rats (250-300g). Two months later, 3mCi of C-11 HED and 2.5µCi of I-131 MIBG were injected via tail vein into infarcted rats and 3 healthy control rats. Animals were sacrificed 5min after tracer injection; then hearts were extracted, frozen and sliced for dual tracer autoradiography and Verhoeff-Van Gieson (VVG) histological scar analysis. To assess the area at risk Evans blue dye was also injected during coronary reocclusion just before the sacrifice. <h3><b>Results</b></h3> In the healthy hearts both MIBG and HED uptake were homogeneously distributed within the myocardium (lateral, anterior, septum, inferior wall (dpm/mm2): 601±202, 554±150, 590±162, 546±152 (HED), 527±113, 551±123, 531±101, 492±118 (MIBG)) showing a gradient from the epicardial to the endocardial portion (epicardial&gt;midcardial&gt;endocardial (dpm/mm2): 699±83* &gt; 596±106* &gt; 422±173 (HED, *vs endocardial p&lt;0.05), 569±79* &gt; 549±124* &gt; 458±117 (MIBG, *vs endocardial P&lt;0.05)). In the infarcted hearts, MIBG defect localization and size were well matched with the scar (3.8±2.3% (MIBG defect) vs. 4.0±2.4% (scar)), whereas it was exceeded by the HED defect (9.1±2.2%, p&lt;0.001). Moreover the area at risk surpassed clearly the HED defect (20.3±6.8%, p&lt;0.05). <h3><b>Conclusions</b></h3> After ischemic injury in rat hearts, we found explicit discrepant uptake between HED and MIBG. The HED defect exceeds the MIBG defect in the area at risk. Although both HED and MIBG are similar catecholamine analogue tracers for sympathetic nerve imaging, they might have different uptake and retention kinetic properties in the ischemically damaged heart