PROTECTIVE EFFECTS OF THE SOD-MIMETIC SC-52608 AGAINST ISCHEMIA REPERFUSION DAMAGE IN THE RABBIT ISOLATED HEART/

An experimental model of myocardial ischemia/reperfusion injury was us ed to assess the cardioprotective effects of SC-52608, a low molecular weight superoxide dismutase mimetic. Langendorff perfused rabbit isol ated hearts were subjected to 30 min of global ischemia followed by 45 min of reperfusion. Hearts perfused in the presence of 20 mu M SC-526 08 exhibited a decrease in the release of creatine kinase and intracel lular potassium compared to hearts receiving vehicle (control). A prog ressive increase in left ventricular end-diastolic pressure developed upon reperfusion in all hearts, but was significantly greater in contr ol hearts when compared to hearts treated with SC-52608 (P < 0.05). In addition, results obtained with a radiolabeled monoclonal antibody to the intracellular protein myosin, indicate an increased degree of irr eversible damage in vehicle-treated hearts. Myocardial protection was not significant in an additional group of hearts treated with 10 mu M SC-52608. The hemodynamic, biochemical, morphological, as well as the antimyosin binding data, demonstrate that pretreatment with SC-52608 p rotects the myocardium from damage associated with global ischemia and reperfusion. The mechanism by which SC-52608 mediates the observed pr otective effect is most likely related to its ability to scavenge supe roxide.