Pharmacology and Therapeutics, Faculty of Medicine,
A progressive impairment in antioxidant status of rabbit hearts was observed when a fixed period (40 mins) of ischemia produced by coronary artery ligation was followed by increasing periods of reperfusion. This was reflected in a reduction in myocardial glutathione levels and an increase in glutathione depletion and production of thiobarbituric acid-reactive substances following in vitro oxidative challenge with t-butylhydroperoxide. Correlation analysis, in which activities of antioxidant enzymes were viewed in relation to biochemical indices of antioxidant status, indicated the functionally relevant suppression of Cu,Zn-superoxide dismutase and glutathione reductase activities in ischemic/reperfused tissues. These results and the demonstration of significant decreases in the activity of glutathione-dependent antioxidant enzymes under acidotic conditions suggest that transient impairment in the functioning of antioxidant enzymes may be involved in the triggering of irreversible myocardial ischemia-reperfusion injury.