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The consequences of sublingual and intravenous nitroglycerin treatment after acute coronary occlusion were studied in 18 closed chest dogs. Intravenous (0.1 mg/min) or sublingual (0.4 mg/15 min) nitroglycerin therapy was instituted 1 hour after occlusion and the effects were observed over a period of 2 hours. Hemodynamics and global and regional cardiac function were measured in both the coronary occluded and nonoccluded segments of the left ventricle before and during coronary occlusion, and after administration of nitroglycerin. A similar nine dog control series was used to establish the significance of the measured effects of nitroglycerin. Intravenous nitroglycerin therapy after 1 hour of occlusion resulted in a marked increase in heart rate (37 ± 12 [mean ± standard error of the mean] percent), reduction of systolic blood pressure (9 ± 3 percent), decrease in left ventricular end-diastolic and end-systolic volumes (32 ± 5 percent and 34 ± 5 percent), increase in coronary sinus flow (64 ± 24 percent) and decrease in left ventricular stroke work (29 ± 8 percent). Sublingually administered nitroglycerin produced similar trends but much less pronounced effects. However, intravenous or sublingual administration of nitroglycerin provided no improvement or caused further deterioration in ischemic region lactate extraction and potassium loss. The left ventricular ejection fraction, which was severely depressed after 1 hour of occlusion, changed minimally after administration of nitroglycerin, and there was no evidence of any correction of regional left ventricular akinesia or dyskinesia. Whereas mean systemic vascular resistance changed minimally as a result of nitroglycerin therapy, it increased 19 ± 8 percent during a corresponding period of an untreated coronary occlusion series suggesting that nitroglycerin prevented an anticipated increase. Postocclusion S-T segment elevation in the electrocardiogram persisted after treatment. Our data corroborated that nitroglycerin reduced left ventricular volumes and increased coronary sinus flow; however, these improvements were accompanied by persisting metabolic and mechanical derangements in the ischemic region.

Hemodynamic and regional metabolic measurements were obtained in seven closed chest dogs during a control period, 3 hours of coronary occlusion and 5 hours of reperfusion. Reperfusion resulted in intermittent ectopic arrhythmias in five dogs and severe shock in two. It usually caused increases in heart rate, coronary sinus flow and maximal isovolumetric rate of rise in left ventricular pressure (dP/dt), which were associated with a decrease in systemic pressure, left ventricular end-diastolic pressure, systemic vascular resistance and stroke work. A transitory increase in cardiac output occurred. Global myocardial oxygen consumption, which was reduced during occlusion, increased with reperfusion. Reperfusion induced abnormal lactate metabolism and myocardial potassium loss in the previously occluded area and often in the nonoccluded segment as well. Histopathologic changes of accelerated necrosis, reactive hyperemia and hemorrhage were often noted after reperfusion. These studies indicate that reperfusion after 3 hours of occlusion caused serious abnormalities in hemodynamic states, metabolic function and morphologic features of the heart.

Two experimental series of closed chest dogs were compared: Group A (five dogs with 7 days of continuous occlusion of the proximal left anterior descending coronary artery); and Group B (six dogs with 7 days of reperfusion after 3 hours of acute occlusion of the same artery). Hemodynamic measurements, ventricular wall motion, coronary sinus blood flow and regional metabolism in both coronary occluded and nonoccluded segments of the left ventricle were measured sequentially. The infarct size was characterized by detailed histopathologic analysis. In the control dogs (Group A), mechanical and metabolic function remained severely depressed after 7 days of occlusion, and mean infarct size was 31.6 percent. In Group B, significant mechanical and metabolic dysfunction developed during 3 hours of occlusion and did not improve during the 1st hour of reperfusion. However, after 7 days of reperfusion, function returned to near preocclusion level. Mean infarct size was 14.2 percent, but in two of the six dogs infarct size was 43 percent and 23 percent, respectively. The study confirmed the unstable character of the early phase of reperfusion, attributed to cell swelling, edema and hemorrhages that resulted in inadequate coronary reflow, arrhythmias and functional derangements. Prolonged reperfusion for 7 days reduced mean infarct size and improved cardiac function.

Focal necrosis (microinfarcts) and regional lactate derangements were observed in closed chest dogs in the nonoccluded (remote) posterior segments of the left and right ventricles after acute occlusion of the proximal left anterior descending coronary artery. Focal infarcts in the remote areas were observed in five of the six dogs with 7 days of occlusion of the left anterior descending artery and in six of seven dogs with 7 days of reperfusion after 3 hours of occlusion. There was a good correlation between the finding of microinfarcts and myocardial lactate derangements in the corresponding remote myocardium. No significant lactate derangements or microinfarcts were found in sham experiments. These findings suggest that ischemia of the remote myocardium frequently accompanies an acute coronary occlusion and may result in irreversible focal lesions.