Effects of vitamin E on prostacyclin release and lipid composition of the ischemic rat heart

Free radical-mediated reperfusion injury has been established as an important mechanism leading to post-ischemic reperfusion myocardial damage. The present study was undertaken to determine the protective role of vitamin E, a membrane-bound free-radical scavenger, on ischemia-reperfusion myocardial injury. After 4 months of feeding a semipurified diet containing 0, 30, and 3000 ppm of R,R,R,-alpha-tocopherol acetate, rat hearts were subjected to Langendorff perfusion. Myocardial damage was judged by the release of creatine phosphokinase (CPK) after 45 min of global ischemia followed by 20 min of reperfusion. Effluent CPK was significantly lowered in the two tocopherol-supplemented groups, although increasing dietary vitamin E by 100-fold above requirement did not confer further protection. However, effluent prostacyclin, detected as the stable metabolite 6-keto-PGF1 alpha by radioimmunoassay, was potentiated by dietary vitamin E in a dose-dependent manner. Analysis of lipids in cardiac subcellular fractions showed considerable enrichment of tocopherol in these membranes by diets, but the levels of polyunsaturated fatty acids, phospholipids, and cholesterol were essentially unchanged by dietary treatment or ischemia-reperfusion. These data demonstrated that requirement level of tocopherol (30 ppm) in the diet is sufficient to protect against reperfusion injury of the myocardium and suggests that tocopherol is important in maintaining cardiac prostacyclin synthesis under conditions of oxygen stress.