The acute and chronic effects of alcohol upon cardiac nucleotide status.

Abstract

The aim of the investigation was to ascertain the biochemical and morphological basis for the functional impairments in the heart due to alcohol. In chronic studies rats were fed a nutritionally complete liquid diet containing 35% of total calories as ethanol, controls were pair-fed identical amounts of the same diet in which ethanol was replaced by isocaloric glucose. In acute studies rats were injected with ethanol at a dose of 75 mmol/kg body weight. Pre-treatment of acute ethanol-dosed rats with cyanamide (ALDH inhibitor) was designed to raise acetaldehyde levels. In chronic studies ventricular adenine nucleotides, ATP, ADP and AMP; NAD(+), ATP ratios and the energy charge showed no alteration after 6 weeks of alcohol feeding. Light and electron microscopy sections indicated very little structural damage to muscle fibres and organelles (especially the mitochondria) in both atria and ventricles. Ventricular fibre diameters, throughout the different ranges, showed no significant differences between chronically alcohol and control-fed rats. In acute studies an increase in ventricular AMP levels (micromoles/g wet weight) occurred following cyanamide and cyanamide + ethanol treatment (+57%, p < 0.025 and +76%, p<0.01, respectively), but not as a consequence of ethanol alone. Cyanamide+ethanol caused marked elevation in ADP levels (+28%, p < 0.05) and again ethanol was without effect. ATP and GTP levels were not altered by any of the acute treatments. The energy charge was slightly reduced in both cyanamide and cyanamide+ethanol groups (-8%, p < 0.01 and -7%, p < 0.05, respectively), but not by ethanol alone. In conclusion, chronic alcohol appears to have minimal effects upon cardiac nucleotides which suggest that possible adaptive mechanisms are induced during the 6-week period and that alternative pathways other than defects in adenine nucleotide concentrations are involved in the pathogenesis of AHMD. The acute study suggests that the heart is resilient to toxic levels of alcohol and acetaldehyde in terms of ATP and GTP levels, despite the elevated AMP, ADP and GDP levels.