Glutamine-containing dipeptides as infusion substrates in the septic state

Abstract

Recently a relationship has been postulated between lowered intracellular glutamine concentrations in the skeletal muscle and the rate of protein synthesis. We investigated the effect of 48 hours of parenteral nutrition supplemented with a solution containing glutamine in free or dipeptide form (alanylglutamine or glycylglutamine) on the intracellular glutamine pool in skeletal muscle and on the hind limb exchange of glutamine in dogs with sepsis after surgery. Before surgery, dogs were fasted for 48 hours. We used glutamine dipeptides as sources because they remain stable in an aqueous solution. Nutrition solutions were isocaloric (17.8 kcal/kg body weight/day on day 1 and 35.6 kcal/kg on day 2) and isonitrogenous (0.33 gm nitrogen/kg body weight/day), providing 2.6 mmol/kg body weight/day as glutamine source. During starvation, muscular free glutamine levels decreased by 41% to 10.4 mmol/L (p less than 0.001). On the second postoperative day the dogs had lowered plasma protein levels, a sharp drop in platelet count, an increase in the leukocyte count, and positive blood cultures. None of the solutions investigated in this study was effective in repleting the glutamine pool during 2 days of postoperative nutrition (11 +/- 2.0 mmol/L without glutamine, 10.3 +/- 2.2 mmol/L with glutamine plus alanine, 9.9 +/- 1.6 mmol/L with alanylglutamine, 7.5 +/- 1.1 mmol/L with glutamine plus glycine, and 7.2 +/- 1.2 mmol/L with glycylglutamine, respectively). The release of glutamine from the hindquarter was 631 +/- 38 nmol/kg body weight/min in the control group and decreased significantly in dogs receiving alanylglutamine (13.5 +/- 45 nmol/kg body weight/min; p less than 0.001) or the constituent amino acids (265 +/- 66 nmol/kg body weight/min; p less than 0.01) but was unchanged in dogs receiving glycylglutamine or glutamine plus glycine. We conclude that the duration and dosage of glutamine administration (equivalent to 26 gm glutamine per day in a patient weighing 70 kg) used in this study are not sufficient to restore glutamine deficiency of the skeletal muscle in the depleted state.