An amino acid mixture rich in branched-chain amino acids and poor in aromatic amino acids was infused in six cirrhotics with altered plasma amino acid profile and normal mental state. The effect on muscle protein catabolism, as measured by urinary excretion of 3-methylhistidine, was assessed during two consecutive 3-day period in which patients received the amino acid mixture alone or in a hypertonic dextrose solution. During a 3-day basal period, cirrhotics showed increased rates of 3-methylhistidine excretion as compared to six matched healthy subjects. Both treatments reduced urinary 3-methylhistidine to normal. During treatment, branched-chain amino acids failed to normalize, plasma aromatic amino acid concentrations and ammonia declined, and alanine increased. Branched-chain amino acids are mainly oxidized in skeletal muscle with production of alanine. Reduced muscle protein catabolism following amino acid infusion is consistent with the physiological role of branched-chain amino acids in suppressing protein breakdown and stimulating protein synthesis. Long-term therapy with branched-chain amino acid-enriched mixtures may prove useful in advanced cirrhotics with severe muscle wasting.

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PubMedDate not supplied

Effect of euglycemic insulin infusion on plasma levels of branched-chain amino acids in cirrhosis.

To test the hypothesis that hyperinsulinism is responsible for reduced branched-chain amino acids in cirrhotics, plasma amino acids were sequentially determined in 8 controls and 8 matched cirrhotics during continuous i.v. insulin infusion. An artificial endocrine pancreas which infused glucose was used to sustain euglycemia. Basal plasma insulin levels were high and branched-chain amino acids were reduced in cirrhotics. Insulin infusion raised insulin levels to 3 to 4 times basal values. During the test, the decline in branched-chain amino acids was markedly higher in controls who had similar steady-state insulin levels. Not only did the level of branched-chain amino acids in controls reach the values seen in cirrhotics after 60 min, but the levels continued to fall at a significantly higher rate throughout the second hour. Glucose consumption and the ratio of glucose infused/steady-state insulin--a measure of tissue sensitivity to insulin--were markedly reduced in cirrhotics and positively correlated with the decline in branched-chain amino acids. In cirrhotics, insulin effects on carbohydrate and branched-chain amino acid metabolism were reduced. Low branched-chain amino acid levels in cirrhotics are not likely to depend only on hyperinsulinism.

Adult↗

PubMedDate not supplied

Galactose elimination capacity and liver volume in aging man.

The galactose elimination capacity, a measure of the functional liver cell mass, and liver volume were measured in 50 normal subjects of five different age groups (less than 50, 51 to 60, 61 to 70, 71 to 80 and greater than 81 years). The volume of the liver was evaluated by ultrasonography. All subjects had normal routine liver function tests and no history of liver disease. Galactose elimination progressively decreased from 3.05 +/- 0.58 (S.D.) mmoles per min in younger subjects to 1.83 +/- 0.24 mmoles per min in subjects over 81 (p less than 0.00003), without any change in the apparent volume of distribution of the sugar. Similarly, the estimated volume of the liver decreased from 110 +/- 14 units to 75 +/- 13 units with increasing age (p less than 0.0002). Both galactose elimination capacity and the estimated liver volume inversely correlated with age (r = -0.728 and r = -0.579, respectively) whereas a positive correlation was observed between galactose elimination and the estimated liver volume (r = 0.520). Part correlation analysis confirmed that age, when entered in a multiple regression already containing body weight and estimated liver volume as independent variables, had a significant effect on liver function, whereas no significant independent effect of liver volume was present. Both age and body weight had a significant independent effect on the estimated liver volume. The maximum functional capacity of the liver, measured by galactose elimination, is reduced in the elderly. Although several factors may play a role, our data suggest that aging is associated with a slight decline in the intrinsic metabolic activity of the hepatic parenchyma.

Adult↗