Combined treatment with vitamins E and C in experimental myocardial infarction in pigs

Abstract

The effect of two different combined treatments with vitamin E acetate and vitamin C on infarct size and recovery of regional myocardial function was investigated in ischemic, reperfused porcine hearts. The left anterior descending coronary artery was distally ligated in 30 thoracotomized pigs for 45 minutes followed by 3 days of reperfusion. Infarct size was determined as the ratio of infarcted (tetrazolium stain) to ischemic (dye technique) myocardium. Regional myocardial function was assessed by sonomicrometry. Ten pigs received vitamin E acetate (12 gm intravenously three times for 1 week) before ischemia and vitamin C (4.4 gm intravenously) before reperfusion (therapy A). Another 10 pigs were treated with vitamin E acetate (12 gm intraarterially) and vitamin C (4.4 gm intravenously) during ischemia (therapy B). An additional 10 pigs served as a control group. Global hemodynamics did not differ significantly among the groups before and during ischemia. Mean plasma concentrations of vitamin E amounted to 107 μg/ml in group A, 16 μg/ml in group B, and 0.9 μg/ml in the control group at the onset of reperfusion. Therapy A reduced the size of the infarct from 73 ± 12% to 47 ± 16% of the region at risk ( p < 0.005) and improved regional systolic shortening from 0 ± 7% to 11 ± 6% at 3 days after reperfusion ( p < 0.01). Therapy B decreased the size of the infarct to 64 ± 9% of the region at risk ( p = 0.05). Regional systolic shortening was not significantly improved by this treatment protocol ( p = 0.18). We conclude that therapy A protects the ischemic, reperfused myocardium probably by scavenging free radicals formed during ischemia and/or during reperfusion. Results of this study do not indicate whether these radicals were generated by jeopardized myocytes or by activated inflammatory cells. Therapy B exhibited only borderline protection. These findings show that cell death of ischemic, reperfused myocytes can be reduced by appropriate treatment with pharmacologic doses of vitamin E acetate and vitamin C.