Sustained Limitation by Superoxide Dismutase of Canine Myocardial Injury Due to Regional Ischemia Followed by Reperfusion

Abstract

Summary: This study was performed to evaluate the effects of superoxide dismutase, a scavenger of superoxide anions, on leukocyte accumulation and myocardial injury in a canine preparation of myocardial infarction. Dogs underwent occlusion of the left circumflex coronary artery for 90 min, followed by a reperfusion for 6 or 24 h. The dogs received either saline or superoxide dismutase (5 mg/kg), beginning 15 min before coronary occlusion and ending 15 min after coronary reflow. Myocardial infarct size, expressed as a percentage of the area at risk, was significantly less in superoxide-dismutase-treated dogs that underwent reperfusion for 6 h, 17.5 ± 1.7, or 24 h, 25.8 ± 3.6, compared to saline-treated dogs that underwent reperfusion for 6 h, 42.7 ± 4.4 (p < 0.05), or 24 h, 53.0 ± 6.1 (p < 0.05). The differences in infarct size were not due to differences in myocardial oxygen demand. Superoxide dismutase had no effect on regional myocardial perfusion of the ischemic bed. Accumulation of ¹¹¹indium (In)-labeled autologous leukocytes within the area at risk was similar in control and superoxide-dismutase-treated dogs (p > 0.05). The results suggest that oxygen radicals play a role in the extent of injury due to regional myocardial ischemia followed by reperfusion, and the protective effect of free radical scavengers may be sustained beyond the expected plasma half-life of the administered agent.