Can superoxide dismutase alter myocardial infarct size?

R eperfusion therapy for acute myocardial infarction reduces myocardial dysfunction and mortality. However, reperfusion can also injure myocardium,' and adjunctive agents have been sought to limit reperfusion injury. After laboratory reports of successful reduction in infarct size by superoxide dismutase (SOD) after ischemia and reperfusion,2-7 SOD became the first of these agents to be used in clinical trials in patients undergoing reperfusion by thrombolysis or percutaneous transluminal angioplasty of acute myocardial infarction. Because of recent conflicting results in laboratory animals,8-13 it seemed appropriate to review the available preclinical studies involving SOD and the rationale for its use during acute myocardial infarction. SOD, discovered by McCord and Fridovitch,14 is an enzyme that catalyzes the conversion of superoxide (univalently reduced oxygen) to the less toxic hydrogen peroxide. Hearse et al'5 described the paradoxical sudden release of enzymes from isolated, perfused hearts triggered by the restoration of oxygen after hypoxia. Granger et al16 and McCord17 proposed that this oxygen paradox was due to the formation of superoxide anion or other partially reduced oxygen species by xanthine oxidase. Xanthine oxidase uses oxygen as an electron acceptor to produce two superoxide anions upon conversion of hypoxanthine to uric acid. The normal endothelial enzyme xanthine dehydrogenase, which uses NAD+ as an electron acceptor, undergoes proteolytic conversion to xanthine oxidase by activation of a calcium-dependent protease upon reperfusion. The superoxide, formed by the catabolism of ATP to hypoxanthine and then to uric acid, could generate the more toxic hydroxyl radical and lead to lipid peroxidation, membrane damage, and cell death.'8 In isolated, buffer-perfused hearts, reperfusion with fluid containing oxygen, but not with anoxic fluid, caused creatine kinase release. SOD and catalase attenuated this injury, and the major source of