Role of free fatty acids in catecholamine-induced cardiac necrosis.
Previous studies have demonstrated that catecholamines produce massiive disseminated cardiac necrosis closely resembling experimental myocardial infarction. Since catecholamine-induced lipolysis increases myocardial oxygen demand and increased levels of FFA are associated with a depression of myocardial function during myocardial hypoxia, the effect of inhibition of lipolysis on myocardial necrosis induced by isoproterenol was studied. Measurements of creatine phosphokinase (CPK) activity in extracts of whole heart homogenates provide a sensitive and relatively specific index of cellular necrosis. Accordingly, CPK activity was measured in rat hearts 48 hours after the animals had received either isoproterenol, given s.c., 3 times at hourly intervals, or isoproterenol after prior administration of nicotinic acid. Control animals were given saline. With increasing doses of isoproterenol, CPK activity in whole heart homogenates was depressed from 21.7 +/- 0.40 in untreated animals (N = 36) to 14.9 +/- 0.46 in animals given the highest dose of isoproterenol (N = 47). In animals in which isoproterenol-induced lipolysis was inhibited by nicotinic acid, CPK was less depressed (16.3 +/- 0.36, N = 47) than with isoproterenol alone (p less 0.02). Nicotinic acid given alone did not interfere with CPK activity. This study suggests that part of the necrosis induced by isoproterenol is due to increased release and oxidation of FFA in the rat heart.
D000818:Animals; D001794:Blood Pressure; D003402:Creatine Kinase / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007545:Isoproterenol / Q000037:antagonists & inhibitors; D008297:Male; D009203:Myocardial Infarction / Q000097:blood / Q000139:chemically induced* / Q000473:pathology; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D009336:Necrosis; D009539:Nicotinic Acids / Q000494:pharmacology; D051381:Rats
D005230:Fatty Acids, Nonesterified; D009539:Nicotinic Acids; D003402:Creatine Kinase; D007545:Isoproterenol