Hypomagnesemia and isoproterenol cardiomyopathies: Protection by probucol

Chronic magnesium deficiency is associated with injury of heart muscle, blood vessels, and neuronal tissue. Despite its clinical significance, the mechanism of magnesium deficiency-induced damage remains unclear. The myocardial necrosis induced by injecting catecholamines, which is augmented by magnesium deficiency, is thought to involve a free radical component through catecholamine autoxidation. α-tocopherol was shown to ameliorate the myocardial necrosis induced by magnesium-deficiency (Freedman et al. BBRC 1990;170:1102-1106), suggesting a role for free radicals in this process. If free-radical injury plays a role in magnesium deficiency, then the catecholamine-associated free-radical production may explain the synergistic myocardial injury between catecholamine and magnesium deficiency. To test the hypothesis that free-radical damage may play a role in magnesium deficiency-induced myocardial necrosis, we investigated the protective effects of probucol, a hypolipidemic agent with antioxidant properties. Hamsters were fed a Mg-deficient diet for 14 days with or without probucol. At the end of this period, some animals were sacrificed, while others were injected with isoproterenol and killed 48 hours later. All hearts were processed for morphometric analysis of the lesions. Changes in serum lipids were also determined. Probucol reduced the size and number of both the isoproterenol- and magnesium deficiency-induced cardiac lesions. Our results suggest that it is probucol's antioxidant property and not its hypolipidemic action that is responsible for this protection.