We have determined the extent to which acute ethanol administration perturbs the synthesis of ventricular contractile and non-contractile proteins in vivo. Male Wistar rats were treated with a standard dose of ethanol (75 mmol kg-1 body weight; i.p.). Controls were treated with isovolumetric amounts of saline (0.15 mol l-1 NaCl). Two metabolic inhibitors of ethanol metabolism were also used namely 4-methylpyrazole (alcohol dehydrogenase inhibitor) and cyanamide (acetaldehyde dehydrogenase inhibitor) which in ethanol-dosed rats have been shown to either decrease or increase acetaldehyde formation, respectively. After 2.5 h, fractional rates of protein synthesis (i.e. the percentage of tissue protein renewed each day) were measured with a large (i.e. 'flooding') dose of L-[4-3H]phenylalanine (150 mumol (100 g)-1 body weight into a lateral vein). This dose of phenylalanine effectively floods all endogenous free amino acid pools so that the specific radioactivity of the free amino acid at the site of protein synthesis (i.e. the amino acyl tRNA) is reflected by the specific radioactivity of the free amino acid in acid-soluble portions of cardiac homogenates. The results showed that ethanol alone and ethanol plus 4-methylpyrazole decreased the fractional rates of mixed, myofibrillar (contractile) and sarcoplasmic (non-contractile) protein synthesis to the same extent (by approx. 25 per cent). Profound inhibition (i.e. 80 per cent) in the fractional rates of mixed, myofibrillar and sarcoplasmic protein synthesis occurred when cyanamide was used to increase acetaldehyde formation. There was also a significant decrease in cardiac DNA content. The results suggest that acute ethanol-induced cardiac injury in the rat may be mediated by both acetaldehyde and ethanol.

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Most studies on the pathological responses of the heart to ethanol have been conducted in isolated systems. The objectives of this study were to determine (1) the synthesis rate of ventricular mitochondrial proteins in vivo and (2) whether the synthesis rates of these proteins are perturbed by acute ethanol exposure in vivo. Fractional rates of protein synthesis [defined as the percentage of tissue protein renewed each day; i.e., ks (%/day)] were determined in male Wistar rats by in vivo injection of a flooding dose of L-[4-3H] phenylalanine. Subsarcolemmal mitochondria were released by polytron treatment, and the isolation of interfibrillar mitochondria involved treatment of the cardiac homogenate with the proteolytic enzyme Nagarse. In the control rats mean ks values of 22.4%/day were observed for mixed cardiac proteins. The synthesis rates of subsarcolemmal and interfibrillar mitochondrial proteins were lower, i.e., 16.9%/day and 10.9%/day, respectively. Acute ethanol administration (75 mmol/kg body weight ip, 2.5 hr) depressed the fractional rate of protein synthesis in all cardiac fractions, including those pertaining to the mitochondria, as follows: mixed fraction--21%, p < 0.01; subsarcolemmal mitochondria--23%, p < 0.01; interfibrillar mitochondria--26%, p < 0.05; and nuclear fraction--20%, p < 0.05. In conclusion, the reduced synthesis rate of the mitochondrial proteins in response to acute ethanol exposure may in some way be partly connected with the depression in myocardial contractility and associated functional damage of mitochondrial metabolism.

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Synthesis of cardiac contractile proteins is selectively sensitive to the effects of acute anaesthesia even in the presence of high plasma insulin concentrations. The fall in cardiac protein synthesis may be a result of the negative inotropic effects of general anaesthesia.