Effect of Inhibition of Lipolysis on Infarct Size After Experimental Coronary Artery Occlusion

Abstract

A B S T R A C T Recent studies have demonstrated a depressant effect of increased delivery of FFA to the hypoxic heart. Because catecholamines are released in acute myocardial infarction, it is likely that lipolytic activity is increased. The purpose of this study was to determine whether inhibition of hormone-sensitive lipases influence the extent and severity of myocardial ischemic injury produced by coronary occlusion. Myocardial infarction was produced by occlusion of the left anterior descending coronary artery in open-chest dogs. 15 min later a surface map of S-T segments was obtained with the use of 10-14 epicardial leads in the distribution area of the occluded artery. Average S-T segment elevation of all sites was used as an index of myocardial ischemic injury. Before coronary occlusion, the average S-T segment elevation was 0.340.2, which increased to 4.1+0.7 mV (SEM, 12 dogs) after occlusion. Inhibition of lipolytic activity by P-pyridyl-carbinol before repeated coronary occlusion reduced the occlusion-induced S-T segment elevation to 2.1+0.6 mV (P <0.001). When arterial concentrations of FFA were raised by i.v. infusion of a triglyceride emulsion and heparin, average S-T segment elevation after coronary occlusion increased from 1.2±0.7 to 2.2±0.8 mV (P < 0.05) in animals treated with P-pyridyl-carbinol, which suggests an unfavorable effect of circulating FFA in this setting. Isoproterenol given before a repeated occlusion increased the severity and extent of the ischemic injury. The effect of isoproterenol on the occlusion-induced S-T segment elevation was reduced, however, when the lipolytic effect of the drug was inhibited by P-pyridyl-carbinol.Our study suggests that P-pyridyl-carbinol during acute coronary artery occlusion may be of importance in reducing the extent and severity of myocardial ischemic injury.

Lipid-membrane interactions and the pathogenesis of ischemic damage in the myocardium.

“…As in the case of a putative negative inotropic effect of these substances, however, negative reports have appeared (Opie et al, 1971;Kostis and Horstmann, 1972;Kostis et al, 1973;Opie and Lubbe, 1975;Most et al, 1977;Ravens and Ravens, 1976). Antilipolytic agents have been reported to reduce the extent and severity of ischemic changes in the epicardial electrocardiogram following acute coronary occlusion (Kjekshus and Mj0s, 1973;Smith and Duce, 1974;Rowe et al, 1974;Russell and Oliver, 1978). Persistent abnormalities in the electrophysiological properties of surviving subendocardial Purkinje fibers after experimental myocardial infarction have been correlated with the appearance of lipid deposits in these cells (Friedman et al, 1975), and lipid accumulation has been implicated in the production of arrhythmias after administration of catecholamines (Mating and Highman, 1958).…”

Effect of Dopamine and Calcium on Lipolysis and Myocardial Ischemic Injury following Acute Coronary Occlusion in the Dog

“…Catecholamine-induced lipolysis is effectively inhibited by nicotinic acid (8,13), and the quantitative importance of excessive myocardial consumption of FFA on the extent of ischemic injury during dopamine infusion was tested in experiments in which coronary artery occlusions were performed before and after inhibition of lipolysis.…”

Importance of Free Fatty Acids as a Determinant of Myocardial Oxygen Consumption and Myocardial Ischemic Injury during Norepinephrine Infusion in Dogs

“…S-T segment elevation has been shown to be reproducible after reocclusion of the vessel after a recovery period of 30 min. It is therefore possible to compare ischemic electrocardiographic changes during different interventions (6,7).…”

“…Thus, isoproterenol has been shown to increase the extent and magnitude of the ischemic injury (6,7), probably due to raised myocardial oxygen demand out of proportion to oxygen supply. The hemodynamic effects of the naturally occurring catecholamine, norepinephrine, are not, however, comparable with those of isoproterenol in that norepinephrine is also a pressor agent.…”

“…Secondly, we proposed to investigate whether the raised oxygen demand of norepinephrine infusion would lead to increased myocardial ischemic injury after acute coronary occlusion as evidenced by epicardial S-T segment elevation (6), and furthermore, whether norepinephrine-induced ischemic changes could be reduced 1 Abbreviations used in this paper: AP, mean aortic blood pressure; CO, cardiac output; dP/dt; maximal value of first derivative of LVP; HR, heart rate; LV'EDP, by inhibition of lipolysis, as shown for isoproterenol (7). If this should be the case, part of a mechanism by which sustained norepinephrine infusion exerts myocardial damage might be explained, and could be pertinent in evaluating its value in the treatment of cardiogenic hypotension in man pretreated with antilipolytic agents.…”