Ferrando A A, Chinkes D L, Wolf S E, Matin S, Herndon D N, Wolfe R R
Department of Surgery, University of Texas Medical Branch, Galveston, USA.
Ann Surg. 1998 Aug;228(2):249-56. doi: 10.1097/00000658-199808000-00015.
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.
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.
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.
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.
These results suggest that acute DCA administration can increase intramuscular glutamine concentration, but that this acute elevation does not affect muscle protein metabolism.
探讨给予二氯乙酸(DCA)刺激丙酮酸氧化是否会增加严重烧伤患者肌肉内谷氨酰胺水平这一假说。
严重损伤后肌肉内谷氨酰胺水平下降,且肌肉内糖酵解和丙酮酸氧化速率升高。肌肉内谷氨酰胺浓度与肌肉蛋白质合成相关。
对5例烧伤面积超过体表面积40%的患者进行了6项研究。在8小时稳定同位素输注期间,对处于进食状态的患者进行研究。5小时后,给予DCA(30mg/kg)30分钟。
对研究5小时和8小时时采集的肌肉活检样本分析显示,给予DCA后细胞内谷氨酰胺水平增加了32%。如通过三池动静脉模型或通过同位素直接掺入骨骼肌蛋白质所确定的,细胞内谷氨酰胺浓度增加并未影响骨骼肌蛋白质合成。给予DCA导致血浆乳酸水平下降,但丙氨酸从头合成或细胞内浓度无变化。
这些结果表明,急性给予DCA可增加肌肉内谷氨酰胺浓度,但这种急性升高并不影响肌肉蛋白质代谢。