Factors Influencing Infarct Size Following Experimental Coronary Artery Occlusions

Abstract

The purpose of this study was the determination of whether hemodynamic and pharmacologic factors influence the extent and severity of myocardial necrosis produced by coronary occlusion. In 48 dogs, 10 to 14 epicardial leads were recorded on the anterior surface of the left ventricle in the distribution and vicinity of the site of occlusion of a branch of the left anterior descending coronary artery. The average S-T segment elevation for each animal was determined at 5-min intervals after occlusion. This elevation was used as an index of the presence and severity of myocardial ischemic injury. The number of sites showing this elevation provided an additional measure of the size of the injured area. Occlusion alone raised the average S-T segment elevation from 0.22 ± 0.04 to 3.32 ± 0.37 mv (SEM). Isoproterenol, ouabain, glucagon, bretylium, and tachycardia given prior to a repeated occlusion increased the severity and extent of ischemic injury, while propranolol decreased it. Elevation of arterial pressure with methoxamine reduced the occlusion-induced S-T segment elevation, and lowering of the mean arterial pressure by hemorrhage had the opposite effect. In 19 additional experiments, propranolol, isoproterenol, and alterations in arterial pressure produced similar alterations in S-T segment elevation when these interventions were applied as long as 3 hr after ligation. In a third group of dogs, myocardial creatine phosphokinase (CPK) activity was determined 24 hr after occlusion at the same sites at which epicardial electrocardiograms were taken. Depression of myocardial CPK activity in injured portions of the left ventricle 24 hr after coronary artery ligation correlated well with S-T segment elevation in the same sites 15 min after ligation. Moreover, isoproterenol increased and propranolol decreased the area of depression of myocardial CPK activity. We conclude that the hemodynamic status and neurohumoral background at the time of occlusion and for up to 3 hr thereafter can alter the extent and severity of myocardial ischemic injury and myocardial necrosis.

Inhalation of concentrated ambient air particles exacerbates myocardial ischemia in conscious dogs.

“…The degree of ischemic injury produced during brief coronary artery occlusion is reflected by changes in the magnitude of ST-segment elevation as well as the overall duration. Several investigators have demonstrated that ST-segment elevation measured early after coronary artery occlusion correlates with reductions in myocardial blood flow (Heng et al 1976;Irvin and Cobb 1977;Kjekshus et al 1972;Wégria et al 1949) and cellular damage as estimated by myocardial creatine phosphokinase activity (Heng et al 1976;Maroko et al 1971). It is now postulated that ST-segment changes are caused by intracellular electrical potential differences between normal and ischemic myocytes during different phases of the cardiac cycle.…”

Precordial ST-segment mapping 1. Clinical studies in the coronary care unit.

“…1 Since such failure appears to be related to the degree of damage sustained by the left ventricle,2 it becomes crucial to assess the magnitude of ischemic injury as early as possible in the clinical course. In experimental studies epicardial and precordial maps have been used to detect and quantitate ischemic damage [3][4][5][6] and to assess the effect of interventions on the degree of ischemic injury. 4 7, 8 These means of limiting the amount of necrosis have also been applied to patients with MI.9U-1 Such interventions require knowledge of natural course of ST deviations in patients.…”

The effect of intravenous nitroglycerin on coronary blood flow and infarct size during myocardial infarction in conscious dogs

“…1977), cobra venom (Maroko er al.. 1978), and reperfusion (Bresnahan et al, 1974;Vatner et al, 1978). Myocardial CK depletion also correlated with attenuation of ultrasound (Mimbs et al, 1977), myocardial IT-palmitate uptake , electrocardiographic evidence of infarction (Maroko et al, 1971), and reduction in coronary flow by the microsphere technique (Kjekshus and Sobel, 1970). We have previously shown that myocardial CK depletion, after coronary occlusion expressed as a percent of left ventricular weight, was reduced by anesthesia (Penkoske et al, 1978) and increased by isoproterenol (Penkoske et al, 1978) compared to controls but unaltered by late administration of verapamil (Karlsberg et al, 1977).…”