OXIDATIVE INJURY IN REOXYGENATED AND REPERFUSED HEARTS

In this study, we separated the effects of low oxygen supply and low c oronary flow in isolated perfused rat hearts to focus on the genesis o f free radicals-induced reperfusion injury. Hearts were exposed to eit her hypoxemia/reoxygenation or ischemia/reperfusion in various sequenc es, with hypoxemia and ischemia matched for duration (20 min), tempera ture (37 degrees C), and oxygen supply (10% of baseline). Hypoxemia/re oxygenation (n = 7) resulted in lower (developed pressure) X (heart ra te) (p <0.001) and higher end-diastolic pressure (p <0.001) than ische mia/reperfusion (n = 9). The presence of 40 IU/ml superoxide dismutase and 104 IU/ml catalase nearly blunted the rise of the end-diastolic p ressure (p = 0.02 vs. baseline), but could only partially prevent the depression of myocardial contractility (p <0.001 vs. baseline, n = 7). Similar patterns were observed when hearts were made ischemic after h ypoxemia, eliminating the intermediate reoxygenation step. We conclude that the major determinant of the reperfusion injury is associated wi th low oxygen supply rather than low coronary flow. Part of the injury is mediated by oxygen-derived free radicals, but a substantial portio n of it is associated with energetic processes.