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 overwhelm 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 postischemic hearts. However, demonstration that GSSG release is due to oxygen radicals and not to other consequences of ischemia/reperfusion is lacking. To address this issue, isolated rabbit hearts underwent 30 min of global ischemia at 37 degrees C. At reflow, control hearts were perfused with standard buffer for 45 min (n = 8); treated hearts received the oxygen radical scavenger superoxide dismutase (hSOD) for 15 min, followed by 30 min of standard perfusion (n = 8). During reperfusion control hearts showed a prominent release of GSSG, which peaked 5 min after 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 negligible. Prevention of oxidative stress was also associated with significantly greater recovery of function. Thus, GSSG release occurs in postischemic hearts as a direct consequence of oxygen radical generation, and it may outlast the initial oxidant load.
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Division of Cardiology, University of Perugia School of Medicine, Italy.
Duilio
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C
Santoro
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Elia
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PP
Cirillo
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P
De Simone
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C
Chiariello
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Ambrosio
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G
D000818:Animals; D001794:Blood Pressure; D003326:Coronary Circulation; D005260:Female; D005609:Free Radicals; D005978:Glutathione / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D007700:Kinetics; D017202:Myocardial Ischemia / Q000378:metabolism*; D015425:Myocardial Reperfusion; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011817:Rabbits; D013482:Superoxide Dismutase / Q000494:pharmacology; D016277:Ventricular Function, Left
D005609:Free Radicals; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005978:Glutathione