Growth hormone modulates amino acid oxidation in the surgical patient: leucine kinetics during the fasted and fed state using moderate nitrogenous and caloric diet and recombinant human growth hormone

Abstract

Twelve patients (aged 70 +/- 9 years) who were scheduled for resection of rectosigmoid colon adenocarcinoma but were otherwise healthy were randomly allocated after surgery to receive either peripheral parenteral nutrition alone ([PPN] n = 6) or in combination with recombinant human growth hormone (rGH) at a daily dose of 0.15 U x kg(-1) x d(-1)(PPN + rGH, n = 6). The daily nutritional regimen was 0.1 g nitrogen x kg(-1) x d(-1) and 20 kcal x kg(-1) x d(-1) (nonprotein energy was supplied as 60% lipid and 40% carbohydrate), and it was maintained for 6 days before and 6 days after surgery. Protein kinetics were studied in all 12 patients during the fasted and fed states before and 6 days after surgery using an 8-hour 13C-leucine tracer infusion. Daily urinary nitrogen, gaseous exchange, and plasma insulin, growth hormone, and insulin-like growth factor-I (IGF-I) were determined before and after surgery. Surgery was responsible for significant increases in postabsorptive whole-body protein flux and synthesis and leucine oxidation (P < .01). Supplementation of PPN with rGH contributed to a significant attenuation of the postoperative increase in leucine oxidation (P = .02), with a significant increase in whole-body protein synthesis (P = .02) and no effect on protein breakdown (P = .40). During the fed state, leucine oxidation increased significantly (P = .005), with the greatest change occurring in the PPN group. Feeding was associated with a significant decrease in whole-body protein breakdown before and after surgery in both groups (P = .001). Postoperative urinary nitrogen excretion was lower but was not statistically significant in the PPN + rGH group compared with the PPN group. There was a significant increase in oxygen consumption (VO2) and carbon dioxide production (VCO2) as a result of feeding and surgery (P < .01). Supplementation with rGH caused a decrease in the respiratory quotient (RQ) (P = .04), particularly after surgery, indicating a direct effect of rGH on fatty acid oxidation. Circulating plasma insulin increased significantly in both groups with feeding and rGH supplementation (P < .05). This was enhanced after surgery, particularly in the rGH group (P < .05). Plasma growth hormone decreased after surgery in the PPN group (P < .05), but did not change as a result of feeding. The circulating levels increased in the PPN + rGH group following subcutaneous administration before or after surgery. Plasma IGF-I decreased after surgery in the PPN group (P < .05), and no changes occurred in the PPN + rGH group with feeding. The present findings suggest a distinct positive effect of rGH on protein synthesis in catabolic patients receiving a moderate intake of nitrogen and calories. This is achieved by modulation of amino acid oxidation. The acute effect of intravenous (IV) nutrients on protein metabolism during the catabolic phase of surgical stress caused a direct decrease in protein breakdown with no effect on protein synthesis.