Do oxygen-derived free radicals, generated at the time of reperfusion, lethally injure viable, previously ischemic myocardium, damage vascular endothelium, and impair recovery of postischemic contractile function? To address these issues, 23 anesthetized open-chest dogs underwent 2 hours of left anterior descending coronary artery occlusion followed by 4 hours of reperfusion. Immediately prior to reflow, each dog was randomized to receive either the free radical scavenging agents superoxide dismutase (SOD) + catalase, or saline alone. SOD + catalase had no significant beneficial effect on infarct size measured by triphenyltetrazolium staining: area of necrosis averaged 38.5 +/- 6.1% vs. 46.3 +/- 6.2% of the area at risk in treated compared with control animals respectively (p = NS). Furthermore, infusion of SOD + catalase did not alter contractile function of the viable subepicardium: mean segment shortening (measured using sonomicrometry) at 4 hours postreperfusion was -23 +/- 5% of baseline, preocclusion values in controls dogs and -24 +/- 9% of preocclusion values in animals that received the scavenging agents. However, SOD + catalase treatment preserved the endocardial microvasculature (assessed by semiquantitative electron microscopic analysis) and enhanced regional myocardial blood flow after reperfusion. Specifically, mean score for microvascular injury was 0.41 +/- 0.14 vs. 0.10 +/- 0.08 (p less than 0.05) in control compared with SOD + catalase treated groups, and blood flow averaged 0.56 +/- 0.11 vs. 1.27 +/- 0.33 ml/min/g tissue (p less than 0.05), respectively, in the previously ischemic endocardium at 2 hours postreflow. Thus, SOD + catalase given at the time of reperfusion had no acute beneficial effect on either the extent of myocyte necrosis or postischemic contractile function in this canine model. SOD + catalase did, however, attenuate both endocardial vascular injury and the "low reflow" phenomenon. These data suggest that microvascular injury and low reflow following prolonged (2 hour) but transient coronary occlusion may be mediated by oxygen-derived free radicals generated at the time of reperfusion.