VITAMIN-E AND OXIDATIVE STRESS IN THE HEART OF THE CARDIOMYOPATHIC SYRIAN-HAMSTER

Myocardial deterioration is relentlessly progressive in almost all pat ients who develop overt symptoms, Many dilated cardiomyopathies are as sociated with a marked increase in cardiac sympathetic tone which may be toxic to myocytes. Microvascular spasm, leading to diffuse, focal r eperfusion injury, also appears to be an important mechanism of cardio myocyte loss in many models of dilated cardiomyopathy. Free radicals m ay mediate both catecholamine-induced damage and reperfusion injury, W e hypothesized that myocardial antioxidant reserve may be significantl y reduced in dilated cardiomyopathy and that alpha-tocopheryl acetate may be of benefit. The enzymes superoxide dismutase, catalase and glut athione peroxidase were measured in the myocardial tissue of control a nd cardiomyopathic hamsters in early (25-50 days) and late (275-320 da ys) stages of the cardiomyopathy. In another study, myocardial glutath ione peroxidase activity and protein oxidation was measured in control and late stage cardiomyopathic hamsters receiving alpha-tocopheryl (7 0 mg/kg/day) or vehicle for 1 month. There were no significant differe nces in glutathione peroxidase activity between control and cardiomyop athic hamsters in the early stage of the cardiomyopathy. Superoxide di smutase and catalase activities did not change with aging; however, gl utathione peroxidase decreased over 30%, alpha-tocopherol was reduced by approximately 50% and protein oxidation increased more than 2-fold in the hearts of late stage cardiomyopathic hamsters. alpha-Tocopheryl acetate administration restored alpha-tocopherol levels, glutathione peroxidase activity and protein oxidation to normal. We conclude that the decompensating heart has significantly limited antioxidant reserve and that this reserve is sensitive to the intake of antioxidant suppl ements. (C) 1998 Elsevier Science Inc.