Canine myocardial reperfusion injury. Its reduction by the combined administration of superoxide dismutase and catalase.

Abstract

SUMMARY. Therapy directed against the toxic effects of reactive oxygen species may reduce the final extent of ischemic injury in otherwise viable tissue irreversibly injured by the abrupt reoxygenation of reperfusion. In four groups of dogs, superoxide dismutase plus catalase (groups I-III) or saline (controls) (group IV) was infused into the left atrium. Group I received the infusion for 2 hours, beginning 15 minutes before occlusion of the left circumflex coronary artery (90 minutes) and ending 15 minutes after reperfusion. Group II received the infusion for 1 hour starring 15 minutes before reperfusion. Group III received the infusion for 1 hour beginning 40 minutes after reperfusion. Dogs were killed the next day, and infarct size was determined by dissection and weighing, and confirmed histologically. Infarct size expressed as percent of the anatomic area at risk was: group I, 19.4 ± 5.0; group II, 21.8 ± 3.3; group III, 47.6 ± 10.3; group IV, 43.6 ± 3.5 (mean ± SEM). Analysis of variance followed by Duncan's multiple range test showed that ultimate infarct size as assessed in groups I and II differed significantly (P < 0.05) from that observed in the control animals in group IV, whereas infarct size between groups III and IV did not differ significantly (P > 0.05). The percent of left ventricle at risk did not differ between the four groups. The beneficial effects of superoxide dismutase plus catalase could not be explained by hemodynamic differences. Similar protection of jeopardized myocardium in groups I and II suggest that potentially viable tissue is salvaged by scavenging free radicals during early reperfusion. Lack of protection in group III suggests that injury has occurred within the first 40 minutes of reperfusion. The results of this investigation demonstrate that the '"primary' myqcardial cellular damage due to ischemia is additive to the cardiac cell damage during the phase of reperfusion, and that the "secondary" effects are mediated by toxic metabolites of oxygen. (Che Res 54: 277-285, 1984)

Myocardial reperfusion: a double-edged sword?

“…The demonstration by Jolly et al (46) that the administration of superoxide dismutase and catalase to dogs with coronary occlusion prior to the onset of reperfusion reduces infarct size, while the failure of these substances to do so when they are administered following the onset of reperfusion, supports the suggestion that reperfusion damage occurs when the previously ischemic heart is reexposed to oxygen.…”

“…Studies in a variety of tissues, including the central nervous system (44), the intestine (45), and the myocardium (46) suggest that oxygen-derived free radicals do contribute importantly to ischemic injury. Severe swelling and lysis of mitochondria in cardiac myocytes and vascular endothelial cells have been demonstrated when isolated cardiac tissue was exposed to solutions capable of generating free radicals (38,40,43).…”

Superoxide dismutase and glutathione peroxidase activities are increased by enalapril and captopril in mouse liver

“…In a model of cardiac ischemia-reperfusion the augmentation of the activities of total SOD and Se-GPx protects from reactive oxygen species-mediated injury [311. SOD and catalase exogenously administered, reduce the cellular lesions caused by myocardial ischemia-reperfusion in dogs [32]. Ldpez-Torres et al found that enhanced levels of CuZn-SOD, glutathione reductase, glutathione and ascorbate, are correlated with higher survival of catalase-inhibited frogs [5].…”

The immune system and cardiac repair

“…Most of the evidence implicating ROS in the pathophysiology of myocardial infarction is derived from investigations using free radical scavengers. Jolly and coworkers [62] demonstrated that the combination of the antioxidant enzymes superoxide dismutase (SOD) and catalase significantly reduced infarct size in dogs undergoing experimental coronary occlusion and reperfusion, when the infusion started before ischemia or 15 min prior to reperfusion. In contrast, no effect was noted when antioxidant infusion was started 40 min after reperfusion, suggesting that free radical-mediated injury is an early event [62].…”

“…Jolly and coworkers [62] demonstrated that the combination of the antioxidant enzymes superoxide dismutase (SOD) and catalase significantly reduced infarct size in dogs undergoing experimental coronary occlusion and reperfusion, when the infusion started before ischemia or 15 min prior to reperfusion. In contrast, no effect was noted when antioxidant infusion was started 40 min after reperfusion, suggesting that free radical-mediated injury is an early event [62]. Other investigators found similar beneficial effects of antioxidant interventions in experimental models of myocardial infarction.…”