Glutamine and α-ketoglutarate prevent the decrease in muscle free glutamine concentration and influence protein synthesis after total hip replacement

Abstract

After surgical trauma, protein synthesis, as well as the concentration of free glutamine in muscle, decreases. Total parenteral nutrition (TPN) alone does not prevent the decrease of glutamine in muscle, but TPN supplemented with glutamine or its precursor, α-ketoglutarate, maintains amino acid concentration in muscle and preserves protein synthesis. The aim of this study was to characterize a human trauma model using patients undergoing total hip replacement, and furthermore to investigate whether glutamine or α-ketoglutarate alone without TPN can prevent the postoperative decrease in muscle free glutamine. Metabolically healthy patients undergoing total hip replacement were randomized into three groups. The control group (n = 13) received glucose 2 g/kg body weight (BW) during surgery and the first 24 postoperative hours. The glutamine group (n = 10) received glucose 2 g/kg BW and glutamine 0.28 g/kg BW, and the α-ketoglutarate group (n = 10) received glucose 2 g/kg BW and α-ketoglutarate 0.28 g/kg BW. Muscle biopsies were performed before surgery and 24 hours postoperatively. Free glutamine concentration in muscle decreased from 11.62 ± 0.67 to 9.80 ± 0.36 mmol /kg wet weight in the control group ( P < .01), whereas it remained unchanged in both the glutamine group and α-ketoglutarate group. Protein synthesis, as reflected by the concentration of total ribosomes, decreased significantly in the control group, but not in glutamine and α-ketoglutarate groups. Polyribosome concentration decreased significantly in both the control and α-ketoglutarate groups. Total hip replacement can be used as a reproducible trauma model, with characteristic changes in the muscle amino acid pattern and protein synthesis 24 hours postoperatively. Glutamine, as well as α-ketoglutarate, attenuated the decrease in free amino acids in muscle tissue after surgical trauma during hypocaloric infusion of glucose.