Multiple systems organ failure: II. The effect of infusion of amino acids and glucose.

Amino acids and dextrose infusion were given for short periods of time to a young man whose basal state is characterized in the previous paper in this series, and their effects were documented in terms of plasma concentrations and splanchnic extraction. The basal state measurements show in the acute trauma state and its subsequent starvation state a largely balanced splanchnic extraction of amino acids but at a decreasing rate. Amino acid (FreAmine) infusion at low rates on this background produced a large increase in extraction of a largely balanced mixture of amino acids but a minimal change in glucose release. The septic state is characterized in both the basal and amino acid infusion state by splanchnic extraction of an unbalanced mixture of amino acids which is deficient in branched-chain amino acids and in relative excess of glucogenic amino acids with increased glucose release and increased utilization of amino acids for gluconeogenesis. In early sepsis this state can largely be repaired by exogenous amino acid infusion but in late sepsis can only be partially repaired. The data suggest that the patient in late sepsis should have a branched-chain rich amino acid mixture and that the hepatic failure of sepsis is strongly associated with peripheral release of an unbalanced mixture of amino acids secondary to enhanced branched-chain catabolism. Infused glucose produces a large increase in the plasma glucose but also improves the balance of the splanchnic amino acids extracted. The statistical validity of the preceding statements are examined in detail in the manuscript.

Plasma concentrations and tissue uptake of free amino acids in dogs in sepsis and starvation: effects of glucose infusion--some effects of low alimentation.

The plasma concentrations of substrates, together with transhepatic and transgut balances, have been studied in six control and eight septic awake fasted dogs. Four severely ill septic dogs (typically fluid in chest and/or abdomen, extensive peritonitis, respiratory difficulties) had high concentrations of threonine, glycine, tyrosine, lysine, histidine, tryptophan, and triglycerides (p less than or equal to 0.05). The other septic dogs (less severely ill) showed fewer and less pronounced alterations in the plasma substrates (aspartate and tryptophan were elevated, p less than or equal to 0.05). The infusion of glucose increased the concentration of glucose, lactate, and pyruvate and depressed the concentrations of most amino acids in both normal and septic dogs. Threonine, asparagine, glutamine, leucine, isoleucine, alpha-aminobutyrate, and tyrosine were significantly depressed in the severely ill septic dogs (p less than or equal to 0.05). In the normal dogs most amino acids were removed by the liver, with alanine accounting for approximately 40% of the total. Glutamine removal was negligible. In the septic dogs hepatic removal of amino acids was variable; livers of two severely ill septic dogs did not remove amino acids. In the control dogs glucose infusion (0.015--0.017 g/kg/min) tended to lower hepatic removal of amino acids. Hepatic dye removal in the septic dogs was always very poor. In the gut glutamine was removed and alanine, glutamate, glycine, and ammonia produced, but the overall sum of amino acid uptake was negligible in both the control and septic dogs. The ratio of tryptophan to the sum of valine, isoleucine, leucine, tyrosine, and phenylalanine concentrations was greatly elevated in all septic dogs in which it was measured. The free concentrations of amino acids in the liver, heart, and muscle tissues were grossly elevated in the low intravenous alimented septic state relative to the fasted normal state, whereas the tissue concentrative ability as measured by nonmetabolizable amino acids, alpha-aminoisobutyrate and cycloleucine, was not similarly increased. Sepsis clearly alters plasma and tissue concentrations, and in some instances hepatic uptake of amino acids.

Turnover of amino acids in sepsis and starvation: Effect of glucose infusion.

The catabolism of glucose and amino acids has been studied in the normal, the fasted, and the fasted septic dog. The fasted septic dog oxidized more glucose and alanine, and had more gluconeogenesis from alanine and the five tritiated amino acids--glutamate, threonine, phenylalanine, leucine, and valine--as compared to the normal and equally fasted dog. Thus the total body protein catabolic state was characterized in biochemical terms. In contrast, following glucose infusion, the fasted septic animal responded much like the fasted animal in terms of decreased animo acid gluconeogenesis and decreased plasma concentrations of amino acids, fats and fat products, but considerably increased the oxidation of alanine. The increased alanine oxidation appeared to be primarily related to increased tissue clearance and increased plasma concentration. There was some suggestive evidence for enhanced oxidation of the tritiated amino acids including leucine and valine during glucose infusion. The protein catabolic state secondary to this sort of sepsis in dogs only on per os fluid support appears to be best characterized as a glucose catabolic state with alanine being oxidized directly. Such states are known to be ones of enhanced metabolic rate secondary to enhanced synthetic processes generally. This is probably related to enhanced sympathetic nervous system release of glucagon with insulin being normally responsive to glucose because of a normal plasma epinephrine.