Relation Between Myocardial Glutathione Content and Extent of Ischemia-Reperfusion Injury

The relation between the extent of myocardial injury sustained during reperfusion and total glutathione (GSH) content in the ischemic myocardium was examined in anesthetized open-chest pigs subjected to coronary occlusion for 45 minutes and reperfusion for 2 hours. In pigs infused with saline during reperfusion (n =6) there was a decrease in myocardial GSH content from 380±48,ug/g in normally perfused myocardium to 182±36,ug/g in the ischemic reperfused myocardium (p<0.02). Myocardial infarct size (expressed as a percentage of the ischemic area) was 12.5±0.8%. There was a delay of recovery of contractile function before returning to 60 % of preocclusion value. In pigs pretreated with buthionine sulfoximine (BSO) (n=5), an inhibitor of cellular GSH synthesis, there was reduction in GSH content to 215±25 gg/gm in normally perfused myocardium and to 77±8,ug/gm in the ischemic reperfused myocardium. The extent of injury was greater as evidenced by an increase in infarct size to 30.4±4.0 % (p<0.001), severe destructive changes in subepicardial ultrastructure, which were absent in saline-infused pigs, and persistence of dyskinesia throughout reperfusion. In pigs infused with glutathione intravenously (0.8 gm/kg) at a rate of 6.5 mg/kg/min (n=6), 5 minutes before and continuously during reperfusion, there was an increase in GSH content to 582+±6