Localization by autoradiography of tritiated isoproterenol in "infarct-like" lesions of rat myocardium.

A number of physiopathogenic mechanisms have been outlined to explain the "infarct-like" lesions produced by isoproterenol (ISP) in the hearts of various animals: Excess of oxygen consumption and inotropic effect, coronary vasoconstriction, deleterious action on glucose and lipid metabolism, direct cardiotoxic effect, platelet aggregation in the small cardiac vessels and formation of microclots, excessive mobilization of fatty acids, fluid and electrolytic imbalances, loss of high-energy intracellular coupling, and inadequate activation of the "calcium pump." For this reason, localization of the tritiated ISP in the normal myocardial fibers and in the induced lesions was studied. The first control group (G-1), consisted of 40 Wistar rats, weighing from 180 to 200 grams; they were injected intraperitoneally with ISP sulfate (10 mg. per kilogram) and were killed under ether anesthesia after periods of 5, 30, and 120 minutes, and 12 and 24 hours. A similar group (G-2) was injected intraperitoneally with an equal dose of ISP plus 5 muCi of tritiated ISP sulfate (3H). In this group animals were killed at the same periods as above. In rats treated with ISP-3H an abundant amount of the labeled drug was observed on the sarcolemma surface and a smaller quantity was noted inside the myocardial fibers. This observation was noted in the autoradiographs obtained 5 minutes after the injection and persisted in all subsequent observation times. In those animals which were killed 5 and 30 minutes after injection, the deposit was noted in "grooves" along the edge of the sarcolemma, strongly suggesting a primary action on the cellular membrane. These findings and the peculiar topography suggest that (1) myocardial necrosis induced by ISP is probably due to an increased activation of the "calcium pump"; the early presence of contracture bands and the positivity of the ischemia test further emphasize this statement; (2) the ISP effect is rapid; (3) the morphologic alterations are similar to those recently described as "coagulation myocytolysis" and present in human infarctions or following sudden death.