[Protective effects of inhibitors of oxygen free radicals on the ischemic and reperfused heart. Applications to cardioplegia]

Abstract

Oxygen free radicals play an important role in the induction of myocardial lesions by the sequence ischaemic-reperfusion. The aim of this study was to determine whether the protection afforded by a cardioplegic solution could be improved by the addition of different anti-oxygen free radical agents. Forty isolated, perfused, rat hearts' isovolumic contraction systems were divided into 5 groups of 8. In 4 groups, cardioplegia was stopped for 90 minutes in normothermia and then reperfused for 45 minutes. These hearts received a single initial injection of either standard cardioplegic solution or a solution enriched with dismutase peroxide (200,000 U/l), reduced glutathione (0.1 mM) or peroxidase (6,000 U/l). The fifth group of hearts was continually aerobically reperfused and served as a non-ischaemic control group. Based on post-ischaemic values of the pressure developed (maximal systolic-diastolic pressure), LVdP/dt, diastolic pressure and coronary flow, the best myocardial protection was observed in those hearts given cardioplegic solution enriched with peroxidase, the haemodynamic indices being comparable to those of the non-ischaemic controls. These results confirm that myocardial protection with cardioplegic solutions can be improved by the addition of anti-oxygen free radical agents, especially peroxidase which inactivates both hydrogen peroxide (precursor of the very cytotoxic hydroxyl radical) and some hydroperoxides, so interrupting the self-sustaining chain of lipidoperoxidation and limiting the damaging effects of this reaction on the cardiac cell membranes.