ACUTE DICHLOROACETATE ADMINISTRATION INCREASES SKELETAL-MUSCLE FREE GLUTAMINE CONCENTRATIONS AFTER BURN INJURY

Objective To investigate the hypothesis that the stimulation of pyruva te oxidation by dichloroacetate (DCA) administration would increase th e level of intramuscular glutamine in severely burned patients Summary Background Data The level of intramuscular glutamine decreases in res ponse to severe injury, and the rate of intramuscular glycolysis and p yruvate oxidation is elevated. Intramuscular glutamine concentrations have been correlated to muscle protein synthesis. Methods Six studies were conducted on five patients with burns >40% total body surface are a. Patients were studied in the fed state during an 8-hour stable isot ope infusion. After 5 hours, DCA (30 mg/kg) was administered for 30 mi nutes. Results analysis of muscle biopsy samples taken at 5 and 8 hour s of the study revealed a 32% increase in intracellular glutamine leve ls after DCA administration. Increased intracellular glutamine concent rations did not effect skeletal muscle protein synthesis as determined by a three-pool arteriovenous model or by the direct incorporation of isotope into skeletal muscle protein. DCA administration resulted in a decrease in plasma lactate but no change in alanine de novo synthesi s or intracellular concentration. Conclusions These results suggest th at acute DCA administration can increase intramuscular glutamine conce ntration, but that this acute elevation does not affect muscle protein metabolism.