REPERFUSION IN ACUTE MYOCARDIAL-INFARCTION - EFFECT OF TIMING AND MODULATING FACTORS IN EXPERIMENTAL-MODELS

Timely reperfusion of Ischemic myocardium in experimental animals halts the advancing trans mural ''wavefront'' of ischemic cell death and thereby limits myocardial infarct she by limiting its transmural extent. The time window of opportunity for such salvage in most experimental models of regional ischemia is the first 3 hours. The number of myocytes that can be salvaged by reperfusion decreases exponentially during this period, such that at 3 hours, reperfusion limits infarct size by only about 10%. The rate of lethal ischemic cell injury and therefore the amount of myocardium that can be salvaged by reperfusion after a particular duration of ischemia is dependent both on the degree of blood flow deficit and the rate of ischemic metabolism. In experimental animal models, several interventions, including hypothermia, calcium antagonists, and ''ischemic preconditioning,'' have been shown to reduce the rate of ischemic metabolism and to limit myocardial infarct size when assessed after a defined period of ischemia and reperfusion. Hypothetically; interventions that could prevent additional myocyte necrosis caused by some deleterious aspects of reperfusion (''lethal reperfusion injury'') also could serve as valuable adjunctive therapy. However, studies of therapies designed to prevent lethal reperfusion injury have produced conflicting results. Thus, the concept that lethal reperfusion injury occurs remains controversial. Experimental evidence indicates that reperfusion accelerates both the initial inflammatory response and later process of infarct repair. Late reperfusion of infarcts in dogs, which does not limit myocardial infarct Size, appears to accelerate the replacement of necrotic myocardium by scar without altering the size of the final scar.