GLUTATHIONE DISULFIDE AS AN INDEX OF OXIDATIVE STRESS DURING POSTISCHEMIC REPERFUSION IN ISOLATED RAT HEARTS

The objectives of this study were to determine 1) whether reactive oxy gen species generated upon postischemic reperfusion lead to oxidative stress in rat hearts, and 2) whether an exogenous prooxidant present i n the early phase of reperfusion causes additional injury. isolated bu ffer-perfused rat hearts were subjected to 30 min of hypothermic no-fl ow ischemia followed by 30 min of reperfusion. Increased myocardial co ntent of glutathione disulfide (GSSG) and increased active transport o f GSSG were used as indices of oxidative stress. To impose a prooxidan t load, cumene hydroperoxide (20 mu M) was administered during the fir st 10 min of reperfusion to a separate group of postischemic hearts. R eperfusion after 30 min of hypothermic ischemia resulted in a recovery of myocardial ATP from 28% at end-ischemia to 50-60%, a release of 5% of total myocardial LDH, and an almost complete recovery of both coro nary flow rate and left ventricular developed pressure. After 5 and 30 min of reperfusion, neither myocardial content of GSSG nor active tra nsport of GSSG were increased. These indices were increased, however, if cumene hydroperoxide was administered during early reperfusion. Aft er stopping the administration of cumene hydroperoxide, myocardial GSS G content returned to control values and GSH content increased, indica ting an unimpaired glutathione reductase reaction. Despite the inducti on of oxidative stress, reperfusion with cumene hydroperoxide did not cause additional metabolic, structural, or functional injury when comp ared to reperfusion without cumene hydroperoxide. We conclude that rea ctive oxygen species generated upon postischemic reperfusion did not l ead to oxidative stress in isolated rat hearts. Moreover, even a super imposed prooxidant load during early reperfusion did not cause additio nal injury.