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Albumin synthesis was studied in the isolated perfused rabbit liver under the influence of the stresses of fasting and acute alcohol and acetaldehyde exposure. Fasting clearly depressed albumin production and disaggregated the endoplasmic membrane-bound polysomes. Acute exposure to alcohol produced the same results. Acetaldehyde 2 mg% resulted in a depression of albumin synthesis but the polysomes were not disaggregated. The metabolism of alcohol was necessary for polysome disaggregation. The acute effects of ethanol and fasting were quite similar and it might be considered that the alcohol was acting like a pharmacologic fast. Employing the liver from a fasted donor specific amino acids infused into the liver at levels of 10 mM reversed the acute effects of fasting and the acute effects of exposure to ethanol. However when the two stresses of fasting and alcohol were combined the same amino acids were not effective. In studying albumin synthesis and/or secretion it is necessary to carefully define the nutritional status of the experimental model.

Although acute perfusion of guinea pig hearts with ethanol does not affect cardiac protein synthesis, the latter is inhibited after prolonged ingestion of ethanol when tested in an in vitro system with the working right ventricle. This study reports on the added stress of ischemia on such hearts. Hearts were removed from maturing guinea pigs after 13-16 weeks of ingesting 10% ethanol and were perfused in vitro under conditions of relative ischemia (one-sixth of normal coronary flow) with maintenance of right ventricular load and outflow resistance identical to normal pre-ischemic levels. With this degree of ischemia, there was a 4-6 fold increase in lactate production, an 80% drop in ATP, and a 90% decrease in creatine phosphate after 150 min of the ischemia. Incorporation of both labeled lysine and phenylalanine into cardiac protein was also diminished to 35% of control in the left ventricle and 55% of control in the right. This diminution of protein synthesis was the same in hearts from ethanol-drinking and matched control animals. Thus, prior prolonged ingestion of ethanol did not worsen the inhibition of protein synthesis by oxygen deprivation. There were, however, two significant differences in hemodynamic response to the ischemia by the right ventricles of hearts from ethanol-drinking guinea pigs compared to their matched controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaldehyde infusions inhibit albumin synthesis in the liver from fed donors but not in the livers from fasted donors. The inhibition of acetaldehyde metabolism with 4-MP and disulfiram reverses this finding, suggesting that acetaldehyde per se is not the toxic agent. Disulfiram stimulates albumin synthesis in livers from fasted donors, and the presence of acetaldehyde does not prevent this process. The effects of ethanol infusions cannot be explained as due to the presence of acetaldehyde; some intermediate metabolic step may be the basis of the inhibition of albumin production and polysome disaggregation in the presence of ethanol.

Newly weaned guinea pigs weighing approximately 300 g were fed normal laboratory diets with drinking water containing 5.5% ethanol as the sole source of liquid for periods of 8-11 weeks. Growth was continuous with this diet. After this period, hearts were removed from anesthetized animals and perfused for 3 hr in a perfusion system in which pressure may be induced in the right ventricle in the face of constant coronary flow. Protein synthesis, assayed from the incorporation of labeled lysine and phenylalanine, was compared to that in hearts from identically treated weight-matched control animals who had been drinking water without ethanol. Protein synthesis in hearts from ethanol-drinking animals was decreased in the right ventricles exposed to normal pulmonary pressure, but was unchanged in the contracting but not working left ventricles. The data suggest that prolonged exposure even to low levels of ethanol in the growing animal may interfere with the cardiac protein synthetic response to the normal work stress.

Prolonged ingestion of ethanol may lead to a cardiomyopathy, and studies in the experimental animal have demonstrated alterations in protein metabolism. These changes include depression of protein synthesis with acetaldehyde in the acute experiment, in vitro, and after chronic ethanol ingestion in vivo. The present studies were initiated to see if the inhibition of protein synthesis following prolonged ethanol ingestion involved myocardial contractile proteins. Newly weaned guinea pigs, weighing 350 g, were placed on a regimen of normal laboratory diet with 10% ethanol in the drinking water. Calorie-matched controls, drinking dextromaltose in the water, were simultaneously run. After 40 weeks of ingesting 10% ethanol in the drinking water, hearts from growing guinea pigs were removed and synthesis of myocardial contractile proteins (myosin heavy chains, light chains (LC1, LC2), actin, and tropomyosin) assayed in vitro with 3H-labeled amino acids. With aging, there was a decrease in the rates of synthesis of all the contractile proteins. After 40 weeks of ethanol ingestion, the synthetic rates of myosin heavy and light chains and tropomyosin were the same as in calorie-matched controls, but the synthetic rate of actin was significantly decreased by 20% (p less than 0.01). This decrease in actin synthesis may be the first indication of ultimate inhibition of synthesis of all the contractile proteins which may lead to myofibrillar disorganization and vacuolization reported after chronic ethanol ingestion.