Acute dichloroacetate administration increases skeletal muscle free glutamine concentrations after burn injury.
OBJECTIVE
To investigate the hypothesis that the stimulation of pyruvate oxidation by dichloroacetate (DCA) administration would increase the level of intramuscular glutamine in severely burned patients.


BACKGROUND
The level of intramuscular glutamine decreases in response to severe injury, and the rate of intramuscular glycolysis and pyruvate 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 area. Patients were studied in the fed state during an 8-hour stable isotope infusion. After 5 hours, DCA (30 mg/kg) was administered for 30 minutes.


RESULTS
Analysis of muscle biopsy samples taken at 5 and 8 hours of the study revealed a 32% increase in intracellular glutamine levels after DCA administration. Increased intracellular glutamine concentrations did not affect 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 synthesis or intracellular concentration.


CONCLUSIONS
These results suggest that acute DCA administration can increase intramuscular glutamine concentration, but that this acute elevation does not affect muscle protein metabolism.
Ferrando
A A
AA
Department of Surgery, University of Texas Medical Branch, Galveston, USA.
Chinkes
D L
DL
Wolf
S E
SE
Matin
S
S
Herndon
D N
DN
Wolfe
R R
RR
D000328:Adult; D000368:Aged; D002056:Burns / Q000378:metabolism*; D003999:Dichloroacetic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005973:Glutamine / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism*
D005973:Glutamine; D003999:Dichloroacetic Acid