O.46 Whole body protein turnover assessed with leucine and glutamine kinetics in vivo at an early stage of human immunodeficiency virus infection

Abstract

0.45 Acute metabolic acidosis decreases muscle protein synthesis and induces negative nitrogen balance in humans G.-R. Kleger 1 , M. A. McNurlan 2, R. Imoberdorf 3, M. Turgay 1, P. J. Garlick 2 and P. E. Ballmer ~ ~Department of Internal Medicine, University of Berne, Beme, Switzerland; 2Department of Surgery, State University of New York at Stony Brook, USA; Department of Medicine, Kantonsspital, St. Gallen, Switzerland, Acute and chronic metabolic acidosis are associated with negative nitrogen balance in cell culture systems and in experimental animals. Recently, we have demonstrated that chronic metabolic acidosis induced negative nitrogen balance and a decrease in albumin synthesis in human subjects [1]. However, the effects of acute metabolic acidosis (AMA) on protein metabolism, in particular on muscle protein synthesis, in humans are so far not well understood. In the present study we have, therefore, measured both muscle protein synthesis and urinary nitrogen excretion in 7 healthy subjects before and during AMA. They were on a constant metabolic diet before (control period) and throughout the whole experiment. AMA was induced by oral ammonium chloride (4.2 mmol/kg body weight per day in 6 divided doses over 48 h). Fractional synthesis rates (FSR) of muscle protein were measured by i.v. injection of L-[2H5ring]phenylalanine (43 mg/kg bw were 7.5 and 15 atom%, respectively). Muscle protein and plasma free phenylalanine enrichments were measured by gas chromatography-mass spectrometry. Nitrogen excretion was determined from 24-h urine collections photometrically after wet incineration, by formation of indophenol with salicylate and hypochlorite. Plasma pH decreased from 7.43 + 0.02 (mean _+ SD), in the control period, to 7.35 _+ 0.04 (P < 0.01 ; paired t-test) in acidosis, and bicarbonate from 24.4 _+ 1.4 mmol/L to 18.0 _+ 3.0 (P < 0.01). FSR of muscle protein decreased in all subjects from an average 1.94 _+ 0.25 %/d to 1.30 _+ 0.39 (P = 0.027), whereas urinary nitrogen excretion increased from 13.9 _+ 2.8 mmol/kg bw to 18.5 _+ 4.0 (P < 0.01). In conclusion, experimental AMA effectively decreased muscle protein synthesis while increasing urinary nitrogen excretion. Whether these effects are directly caused by acidosis or mediated by other factors such as a decrease in IGF-1 [1] remains to be shown. Early correction of AMA in acutely ill patients might restrict protein wasting and preserve muscle mass. Reference: [1] Ballmer PE et al. J Clin Invest 1995; 95: 39-45.