Evidence for Free Radical Generation in Vivo during Cardiac Ischemia and Reperfusion
Myocardial stunning results from reperfusion of a zone of heart muscle that has been subjected to ischemia for a period of less than 20 min (10). Although stunning usually results in temporary disruption of heart function, it does not appear to result in death of myocytes which is characteristic of longer periods of ischemia followed by reperfusion (21). Recovery of viable tissue in the reperfused zone after more extensive periods of ischemia is a function of the time of coronary occlusion. Based on the observation of a number of investigators, it became apparent that reoxygenation of anoxic tissues was detrimental to those tissues, but not as detrimental as would be the case if there were no reoxygenation at all. The oxygen paradox concept was set forth by Hearse and colleagues (8) who determined that there were ultra-structural changes in myocytes which occurred as a result of reoxygenation of ischemic heart tissue (9). Other investigations suggested that oxygen free radicals might be involved in reperfusion injury to tissues in general due to the conversion of xanthine dehydrogenase to xanthine oxidase during ischemia (7). In addition, other possible sources of radical production have been implicated, including activated neutrophils (22,23) and cellular redox functions such as the mitochondrial transport system (17) and eicosanoid metabolism (5,24). Factors which inhibit or modulate the in vitro activities of these various sources of radical production and which have been reported to provide some protection against reperfusion tissue injury when administered in vivo constitute the basis for the implications (prostaglandin synthesis inhibitors, superoxide dismutase (15), oxypurinol (19), free radical scavengers (16), iron chelators (3), etc.).
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