Effects of ethanol metabolites on intermediary metabolism in heart muscle.

Isolated rat hearts were perfused by the Langendorff procedure to study the metabolic effects of ethanol, acetaldehyde and acetate on the myocardium. Ethanol caused a slight decrease in the work output of the heart and concomitant changes in the oxygen consumption and cellular redox state. A low-Km (1 microM) acetaldehyde dehydrogenase activity was found in rat heart mitochondria, but an acetaldehyde concentration of 50 microM or higher was necessary to reduce tissue NAD+ in the isolated perfused heart. One hundred microM or higher concentrations of acetaldehyde caused an increase in the work output of the heart, with a concomitant oxidation of NADH. Acetaldehyde at a 50 microM concentration did not affect myocardial lipid metabolism. Acetate caused a reduction of mitochondrial NAD+, an increase in the coronary flow and an increase in the O2 consumption of the perfused heart. Practically all of the oxygen consumption could be accounted for by acetate oxidation. A 2 mM concentration of acetate inhibited the oxidation of oleate by 35% and stimulated oleate incorporation into myocardial lipids by 90%; therefore, it appears that the acute metabolic derangements of the heart muscle during ethanol metabolism in vivo are probably mainly caused by acetate.