Myocardial sulfhydryl (SH)-containing compounds, including reduced glutathione (GSH), are both defenses against and potential markers of reactive oxygen metabolite injury during ischemia and reperfusion. We examined the alterations in GSH and other myocardial SH pools during reperfusion in anesthetized dogs exposed to brief (15 minutes, n=7) or prolonged (90 minutes, n=6) regional ischemia caused by occlusion of the left anterior descending artery. Ninety minutes of ischemia followed by 5 hours

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... of reperfusion, which resulted in myocardial necrosis of 43.9±4.0% of the area at risk, caused a 22% reduction in total myocardial SH groups (p<0.01), a 57% decrease in nonprotein myocardial SH groups (p<0.01), a 56% decrease in GSH (p<0.01), and a 62% decrease in non-GSH, nonprotein SH groups (p<0.02). However, protein SH groups were not significantly reduced (12% decrease, p=NS). Also, myocardial release of GSH and oxidized glutathione (GSSG) into the coronary venous effluent occurred during early reperfusion. In contrast, 15 minutes of ischemia, followed by 30 minutes of reperfusion, did not alter myocardial total SH groups, protein SH groups, or GSH (9% decrease, p=NS); nor was there reperfusion release of GSH or GSSG. However, even with brief ischemia, nonprotein SH groups decreased 23% (p<0.05), due mainly to a 59% decrease in the non-GSH, nonprotein SH pool (p<0.05). These changes after brief ischemia occurred without alterations in myocardial GSSG or the GSH/GSSG ratio. Thus, the pattern of depletion of myocardial SH pools during reperfusion differs depending on the duration of the preceding ischemia. The decreases in nonprotein SH and in non-GSH, nonprotein SH pools did not occur (9% decrease and 3% decrease, respectively; both p =NS) in dogs subjected to brief occlusion (n =6) that were treated before coronary occlusion with 500 mg/kg i.v. dimethylthiourea, an intracellular scavenger of H202 and *OH. Since only the non-GSH, nonprotein SH pool decreased significantly after brief ischemia and since this decrease could be prevented by antioxidant intervention, this pool appears to be the most sensitive SH indicator of reactive oxygen metabolite-induced myocardial ischemia/ reperfusion injury. (Circulation Research 1991:68:605-613) From the defenses against injury caused by reactive oxygen metabolites,7-10 and alterations in myocardial SH pools may be markers of this injury. The most frequently studied SH pool is glutathione (GSH), the cofactor for the enzyme glutathione peroxidase. GSH is oxidized to GSSG during metabolism of hydrogen peroxide7 and lipid peroxides"1 by glutathione peroxidase. GSH also decreases membrane lipid peroxide formation,.1213 reacts with superoxide'4 and other free radicals,15 and maintains protein SH groups in their reduced state.16-18 Thus, GSH can protect against reactive oxygen metabolite-induced myocardial injury by several mechanisms. Although previous investigation9'19-21 has focused on the role of GSH, changes in other myocardial SH pools could occur, either in concert with or independent of changes in GSH. The role of other SH pools by guest on