SUMMARY. Previous studies demonstrated a significant reduction of ultimate infarct size in the canine heart by the combined administration of superoxide dismutase plus catalase. This study was performed to assess the independent effects of each enzyme on ultimate infarct size due to ischemia/reperfusion. Dogs received 2-hour infusions of superoxide dismutase, catalase, or albumin (controls) via the left atrium beginning 15 minutes before and ending 15 minutes after a 90-minute occlusion of the left circumflex coronary artery. The dogs were killed 6 hours after reperfusion. After histochemical staining, infarct and risk area masses were calculated by gravimetric and planimetric analysis. Infarct size expressed as a percentage of the area at risk was: superoxide dismutase, 19 ± 5; catalase, 30 ± 5; and controls, 40 ± 3. Infarct size in the superoxide dismutase group, but not the catalase group, was significantly less than in controls (P < 0.05). No significant differences in hemodynamics or area at risk were observed that could explain the differences in infarct size. The results indicate that superoxide dismutase alone protects reperfused ischemic myocardium as well as does the combination of superoxide dismutase and catalase. The beneficial effect of superoxide dismutase and insignificant effect of catalase suggest that tissue damage during ischemia and reperfusion may be mediated largely by superoxide anion but not by hydrogen peroxide. (Circ Res 56: 895-898, 1985) TISSUE injury resulting from a variety of causes is attributable to the toxic effects upon biological systems of reactive oxygen species, such as superoxide anion (-C^"), hydrogen peroxide (H 2 O 2 ), and hydroxyl radical (OH) (Freeman and Crapo, 1982). Studies of intestinal (Parks et al., 1982), cerebral (Demopoulous et al., 1980), and global cardiac (Shlafer et al., 1982;Gardner et al., 1983) ischemia implicate oxygen-free radicals in the development of ischemic tissue injury.Previous experiments reported by this laboratory investigated the effects upon regional myocardial ischemia of the combined administration of superoxide dismutase (superoxide oxidoreductase EC 1.15.1.1) and catalase (H 2 O 2 :H 2 O 2 oxidoreductase EC 1.11.1.6), enzymes which are endogenous scavengers of O 2~ and hhO^ respectively. In a canine model of myocardial infarction, the combination achieved a 50% reduction of infarct size assessed 24 hours after a 90-minute circumflex coronary artery (LCX) occlusion followed by reperfusion. Although the results suggest that myocardial necrosis due to coronary occlusion and reperfusion may be limited by free radical scavengers, the relative importance of -O 2~ and H 2 O 2 in the pathophysiological process could not be deduced. Therefore, this study was performed to determine the effect of either enzyme on the extent of myocardial injury after ischemia and reperfusion.
MethodsDetailed methods have been published previously (Romson et al., 1983). Briefly, male mongrel dogs (12-15 kg) were anesthetized with Dial-urethane (0.6 ml/kg, i...