Effect of inhibition of lipolysis on infarct size after experimental coronary artery occlusion.
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 0.3+/-0.2, which increased to 4.1+/-0.7 mV (SEM, 12 dogs) after occlusion. Inhibition of lipolytic activity by beta-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 beta-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 beta-pyridyl-carbinol. Our study suggests that beta-pyridyl-carbinol during acute coronary artery occlusion may be of importance in reducing the extent and severity of myocardial ischemic injury.
D000818:Animals; D001794:Blood Pressure; D003326:Coronary Circulation / Q000187:drug effects*; D003402:Creatine Kinase / Q000032:analysis; D004285:Dogs; D004562:Electrocardiography; D005230:Fatty Acids, Nonesterified / Q000097:blood; D006339:Heart Rate; D006493:Heparin / Q000494:pharmacology; D007545:Isoproterenol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000432:Methanol / Q000494:pharmacology*; D009203:Myocardial Infarction; D009206:Myocardium / Q000201:enzymology; D011725:Pyridines / Q000494:pharmacology*; D014280:Triglycerides / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects
D005230:Fatty Acids, Nonesterified; D011725:Pyridines; D014280:Triglycerides; D006493:Heparin; D003402:Creatine Kinase; D007545:Isoproterenol; D000432:Methanol