TRAUMA: REGULATORS AND MODULATORS OF THE CATABOLIC STAT

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(1) To determine the regulation of amino acid release from skeletal muscle and identify the altered control mechanisms following stress and trauma. To determine the influence of ketone bodies, branched chain amino acids, and various hormones on these mechanisms. (2) To characterize hormone fuel fluxes and their control across skeletal muscle bed in various states. To determine the effect of nutrients and hormones on these substrate fluxes. (3) To determine the effects of parenteral nutrition on fuel oxidation, storage and protein synthesis in critically ill traumatized patients and then elucidate the mechanisms which regulate these processes. To determine the effect of euglycemia and hyperglycemia during glucose administration on hepatic glucose and fat balance, organ distribution and metabolic handling of other nutrients administered with the glucose infusion. (4) To determine the optimal timing of oral and intravenous nutrient administration and the influence of exercise to maximize weight gain and nitrogen balance. (5) To determine the effects of maximal nutritional support on impaired cellular function noted in patients after surgical operations and trauma and characterize the site of production of the circulating immunosuppressive factors. Molecular mechanisms will be determined in myoblast tissue cultures and analysis of biopsies taken from the hindlimb of the dog. Fuel flux studies will be done in the dog and injured patients. The effect of exercise and timing of feeding will be determined in the squirrel monkey. The effect of nutritional support on immunity will be performed in patients. Localization of the production of circulating immunosuppressive factors will be performed in sheep.