OBJECTIVE: Administration of recombinant human growth hormone (rhGH) to critically ill adults in an attempt to attenuate catabolism was associated with increased morbidity and mortality. Possible explanations included inhibition of glutamine release from skeletal muscle and consequent restriction of splanchnic glutamine supply. In this study, we examined the effects of rhGH on plasma glutamine levels and on muscle and liver glutamine concentrations and protein synthesis rates in sepsis. We investigated the possibility that administration of supplemental glutamine might ameliorate any adverse effects of rhGH. DESIGN: Prospective study in rats rendered septic by cecal ligation and puncture. SETTING: University hospital laboratory. SUBJECTS: A total of 78 male Wistar rats in six groups. INTERVENTIONS: Animals received 6-hr tail vein infusions, commencing 18 hrs after cecal ligation and puncture, of either (a) 0.9% sodium chloride, (b) a standard parenteral nutrition (PN) solution without glutamine, or (c) an isocaloric, isonitrogenous PN solution with glutamine. PN groups received 400 microg rhGH or equivolume 0.9% sodium chloride vehicle in a divided subcutaneous and intravenous dose at PN commencement. Sacrifice was at the end of the infusion period. A further group was unoperated and uninfused and killed at 24 hrs as baseline controls. MEASUREMENTS AND MAIN RESULTS: Glutamine concentrations were measured by fluorometry. Protein synthesis in muscle and liver was measured by a "flooding-dose" technique employing L-[4-H]phenylalanine. Plasma glutamine was increased after cecal ligation and puncture except in the saline and glutamine with rhGH animals. Muscle glutamine was reduced after cecal ligation and puncture and was significantly lower in animals receiving standard PN with rhGH vs. saline alone. Liver glutamine was increased in animals receiving saline and those receiving standard PN with rhGH. PN, with or without glutamine, increased muscle protein synthesis, and the administration of rhGH tended to further increase this effect. Neither PN, glutamine, nor rhGH had an effect on the increased liver protein synthesis characteristic of sepsis. CONCLUSIONS: In sepsis, increased muscle protein synthesis with PN and rhGH administration is not associated with increased muscle glutamine levels. Administration of rhGH does not result in reduced liver glutamine levels or rates of hepatic protein synthesis. PN containing glutamine was no more efficacious than standard PN at increasing muscle protein synthesis.
OBJECTIVE: Administration of recombinant humangrowth hormone (rhGH) to critically ill adults in an attempt to attenuate catabolism was associated with increased morbidity and mortality. Possible explanations included inhibition of glutamine release from skeletal muscle and consequent restriction of splanchnic glutamine supply. In this study, we examined the effects of rhGH on plasma glutamine levels and on muscle and liver glutamine concentrations and protein synthesis rates in sepsis. We investigated the possibility that administration of supplemental glutamine might ameliorate any adverse effects of rhGH. DESIGN: Prospective study in rats rendered septic by cecal ligation and puncture. SETTING: University hospital laboratory. SUBJECTS: A total of 78 male Wistar rats in six groups. INTERVENTIONS: Animals received 6-hr tail vein infusions, commencing 18 hrs after cecal ligation and puncture, of either (a) 0.9% sodium chloride, (b) a standard parenteral nutrition (PN) solution without glutamine, or (c) an isocaloric, isonitrogenous PN solution with glutamine. PN groups received 400 microg rhGH or equivolume 0.9% sodium chloride vehicle in a divided subcutaneous and intravenous dose at PN commencement. Sacrifice was at the end of the infusion period. A further group was unoperated and uninfused and killed at 24 hrs as baseline controls. MEASUREMENTS AND MAIN RESULTS:Glutamine concentrations were measured by fluorometry. Protein synthesis in muscle and liver was measured by a "flooding-dose" technique employing L-[4-H]phenylalanine. Plasma glutamine was increased after cecal ligation and puncture except in the saline and glutamine with rhGH animals. Muscle glutamine was reduced after cecal ligation and puncture and was significantly lower in animals receiving standard PN with rhGH vs. saline alone. Liver glutamine was increased in animals receiving saline and those receiving standard PN with rhGH. PN, with or without glutamine, increased muscle protein synthesis, and the administration of rhGH tended to further increase this effect. Neither PN, glutamine, nor rhGH had an effect on the increased liver protein synthesis characteristic of sepsis. CONCLUSIONS: In sepsis, increased muscle protein synthesis with PN and rhGH administration is not associated with increased muscle glutamine levels. Administration of rhGH does not result in reduced liver glutamine levels or rates of hepatic protein synthesis. PN containing glutamine was no more efficacious than standard PN at increasing muscle protein synthesis.