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The cause of alcoholic myocardiopathy is unknown. The effects of acute exposure to ethanol or its metabolite acetaldehyde on protein synthesis in working, intact, guinea pig hearts in vitro were studied utilizing lysine-(14)C perfusion. Ethanol at 250 mg/100 ml, a level sufficient to markedly inhibit hepatic production of albumin, did not alter cardiac function, the equilibration of the intracellular free lysine pool in either ventricle, or the incorporation of lysine-(14)C into protein. Thus, in controls and ethanol-perfused hearts, the incorporation of lysine in 3 hr was 44.1+/-1.5 and 42.8+/-1.2 mumoles lysine/g protein N for the right ventricles and 25.6+/-1.0 and 24.3+/-0.8 for the left ventricles, respectively. Only at lethal levels, 1500 mg/100 ml ethanol, was protein synthesis depressed. Acetaldehyde 3.5 mg/100 ml (0.8 mM) effected a markedly positive chronotropic and inotropic effect on the perfused heart and slightly depressed equilibration of the intracellular free lysine pool. However, determinations of protein incorporation of lysine-(14)C based on intracellular lysine-(14)C specific activities showed a significant decrease from control right and left ventricle values, to 27.1+/-2.8 and 14.9+/-1.9. Propanalol, which abolished the chronotropic effect, did not prevent the inhibition of protein synthesis. The studies suggest that acetaldehyde, which inhibits cardiac protein synthesis in vitro, may play a role in alcoholic myocardiopathy by interfering with normal myocardial protein synthesis.

The synthesis of serum albumin was measured in 19 patients with cirrhosis of the liver and ascites. Carbonate-(14)C was used to label the guanido carbon of arginine in albumin.18 of the patients had the diagnosis of cirrhosis confirmed by biopsy and/or by the presence of esophageal varices. Seven patients with albumin synthesis rates of 42-105 mg/kg per day demonstrated the lowest serum cholesterol esters and highest serum glutamic oxalacetic transaminase (SGOT) levels, while the seven patients whose albumin synthesis rates ranged from 203-378 mg/kg per day, had significantly higher cholesterol ester levels and significantly lower values for SGOT. The serum albumin levels were equally depressed in all patients. In patients with cirrhosis and ascites albumin production was found to be normal or elevated in seven of the 19 subjects, and only markedly depressed in seven patients, in spite of the fact that the serum albumin level was depressed in all patients.

1. In rheumatic myocarditis, foci, termed submiliary nodules of Aschoff, are present which are characteristic of the rheumatic infection. 2. They are most frequently found in the walls of the left ventricle, the auricles usually escaping. 3. The nodules were found in three cases of chorea without joint manifestations, proving the close relation of this condition to rheumatism. 4. They were absent in fourteen cases of subacute bacterial endocarditis due to Streptococcus mitis. 5. They were not found in infections of the endocardium with the gonococcus, staphylococcus, streptococcus, or pneumococcus. 6. Even in the absence of a rheumatic history we believe, in accordance with Fraenkel, that the presence of Aschoff bodies signifies a previous rheumatic infection. 7. Aschoff bodies are not always found in rheumatic carditis, where the infection antedates death by a long period, but the healed remains, represented by sclerotic patches ("Schwielen"), are present. 8. We suggest that the cases of arthritis characterized by the presence of the submiliary nodules of Aschoff in the myocardium be placed in one group and called for the time being "rheumatism"; and the cases with articular manifestations, yielding positive bacteriological findings and no Aschoff bodies, should be classified according to the infecting microörganisms concerned, and not as rheumatism.

The effects of CCl(4) on albumin synthesis were studied employing the isolated perfused liver. Carbonate-(14)C was used to measure newly synthesized albumin. 2.5 ml of CCl(4) was administered by stomach tube 2 hr before perfusion. Albumin synthesis decreased from 36 to 5 mg following the ingestion of CCl(4). Preperfusing the livers for 1 hr before measuring albumin synthesis resulted in an increase to 12 mg, and the addition of tryptophan to a final concentration of 10 mM resulted in a further increase to 19 mg. Cortisone did not protect against the toxic effects of CCl(4) when administered to the donor rabbits. Fasting resulted in an increased sensitivity to CCl(4) and an antioxidant was not effective in protecting against the toxic manifestations of CCl(4).

1. By the intravenous injection into rabbits of Streptococcus mitis, we have produced focalized myocardial lesions which are identical with those caused by the injection of Streptococcus rheumaticus, and with those produced by Bracht and Wächter with Streptococcus viridans. 2. The lesions differ from those which we produced by injections of streptococci from the Chicago epidemic of sore throat (epidemic streptococcus). 3. The lesions are not identical with Aschoff bodies and are easily differentiated from them. They also differ from the foci produced by Jackson and Coombs, who describe their lesions as being either Aschoff bodies or similar formations. 4. The myocardial lesions of the rabbit appear to be caused by toxins liberated by the streptococci injected and not by the living organisms themselves. 5. The only point of similarity between the experimental lesions and those found in cases of rheumatic carditis in man is their focalized nature.

Carbonate-(14)C was used to label the hepatic intracellular arginine pool and direct measurement of albumin synthesis was made in six rabbits before and after an 18-36 hr fast. 18 perfusion studies were performed with livers derived from fed and fasted rabbits (18-24 hr). Microsomal amino acid-incorporating ability with leucine-(3)H and phenylalanine-(14)C was compared in 17 studies, using microsomes isolated from livers taken from fed and fasted rabbits and from isolated perfused livers whose donors were fed and fasted. Albumin synthesis is rapidly inhibited by fasting. Albumin synthesis decreased 33% in vivo and 53% in the perfused liver. The microsomes from perfused livers taken from fed animals did not demonstrate a significantly reduced capacity to incorporate leucine-(3)H or phenylalanine-(14)C into protein. Microsomes derived from perfused and nonperfused livers whose donors were fasted incorporated 32-54% less tracer than microsomes obtained from fed donor rabbits. Microsomes separated from perfused livers removed from fed and fasted rabbits responded to polyuridylic acid stimulation and phenylalanine-(14)C incorporation rose from 58 to 171%. An 18-36 hr fast inhibits albumin production in vivo and in the perfused liver. The microsomal system is less active in the fasted state and perfusion per se does not inhibit the microsomal response.