A SHORT BURST OF OXYGEN RADICALS AT REFLOW INDUCES SUSTAINED-RELEASE OF OXIDIZED GLUTATHIONE FROM POSTISCHEMIC HEARTS

Oxygen radical generation induced by postischemic reperfusion can over whelm endogenous radical scavenging systems, resulting in ''oxidative stress.'' Release of oxidized glutathione (GSSG) upon reflow has been taken as evidence for the occurrence of oxidative stress in postischem ic hearts. However, demonstration that GSSG release is due to oxygen r adicals and not to other consequences of ischemia/reperfusion is lacki ng. To address this issue, isolated rabbit hearts underwent 30 min of global ischemia at 37 degrees C. At reflow, control hearts were perfus ed with standard buffer for 45 min (n = 8); treated hearts received th e oxygen radical scavenger superoxide dismutase (hSOD) for 15 min, fol lowed by 30 min of standard perfusion (n = 8). During reperfusion cont rol hearts showed a prominent release of GSSG, which peaked 5 min afte r reflow. Interestingly, GSSG release was still significantly elevated 45 min into reperfusion, at a time when oxygen radical generation has long ceased. In contrast, in hSOD-treated hearts GSSG release was neg ligible, Prevention of oxidative stress was also associated with signi ficantly greater recovery of function. Thus, GSSG release occurs in po stischemic hearts as a direct consequence of oxygen radical generation , and it may outlast the initial oxidant load. (C) 1998 Elsevier Scien ce Inc.