New theory on the pathogenesis of acute myocardial infarction

Autopsy studies of hearts from 140 patients who had suffered acute myocardial infarction (AMI) and 26 cases of sudden coronary death revealed two distinct types of myocardial cell death: "kinetic cell death" (KD) and "static cell death" (SD). In KD, the predominant type of cell death in AMI-myofibrils disintegrated through alternating overcontraction and overextension. KD was found not only in patients having died after some time had elapsed from the onset of AMI, but also in cases of sudden coronary death. Muscle fibers in SD, which by contrast began to appear at least seven hours after the onset of AMI, characteristically preserved cross striations, while their nuclei were pyknotic or had already disappeared. Such fibers were observed only in territories peripheral to occlusive coronary thrombus, a secondary rather than a primary event that takes place during the course of AMI. As a result of the above observations, we were able to produce a new experimental model of AMI using mongrel dogs. As a preparatory procedure we first injected them intravenously with 2% calcium chloride at a constant rate for 90 or 120 minutes, and then with a sudden injection of caffeine, calcium chloride and catecholamine in order to induce KD. In contrast, ligation of the intraventricular coronary artery near its origin caused SD of myocardial fibers in the dependent territories. Overall results led us to conclude that AMI is initiated by instantaneous overcontraction of myocardial fibers, resulting in their KD, a phenomenon that could be called "myocardial self-destruction."