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

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 parenter al nutrition alone ([PPN] n = 6) or in combination with recombinant hu man growth hormone (rGH) at a daily dose of 0.15 U . kg(-1). d(-1) (PP N + rGH, n = 6). The daily nutritional regimen was 0.1 g nitrogen . kg (-1). d(-1) and 20 kcal . kg(-1). d(-1) (nonprotein energy was supplie d 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 C-13-leucine tracer infusion. Daily urinary ni trogen, gaseous exchange, and plasma insulin, growth hormone, and insu lin-like growth factor-I (IGF-I) were determined before and after surg ery. Surgery was responsible for significant increases in postabsorpti ve whole-body protein flux and synthesis and leucine oxidation (P < .0 1). Supplementation of PPN with rGH contributed to a significant atten uation of the postoperative increase in leucine oxidation (P = .02), w ith a significant increase in whole-body protein synthesis (P = .02) a nd no effect on protein breakdown (P = .40). During the fed state, leu cine oxidation increased significantly (P = .005), with the greatest c hange occurring in the PPN group. Feeding was associated with a signif icant decrease in whole-body protein breakdown before and after surger y 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 oxyg en consumption (Vo(2)) and carbon dioxide production (Vco(2)) as a res ult of feeding and surgery (P < .01). Supplementation with rGH caused a decrease in the respiratory quotient (RO) (P = .04), particularly af ter surgery, indicating a direct effect of rGH on fatty acid oxidation . Circulating plasma insulin increased significantly in both groups wi th feeding and rGH supplementation (P < .05). This was enhanced after surgery, particularly in the rGH group (P < .05). Plasma growth hormon e decreased after surgery in the PPN group (P < .05), but did not chan ge as a result of feeding. The circulating levels increased in the PPN + rGH group following subcutaneous administration before or after sur gery. Plasma IGF-I decreased after surgery in the PPN group (P < .05), and no changes occurred in the PPN + rGH group with feeding. The pres ent findings suggest a distinct positive effect of rGH on protein synt hesis in catabolic patients receiving a moderate intake of nitrogen an d calories. This is achieved by modulation of amino acid oxidation. Th e acute effect of intravenous (IV) nutrients on protein metabolism dur ing the catabolic phase of surgical stress caused a direct decrease in protein breakdown with no effect on protein synthesis. Copyright (C) 1997 by W.B. Saunders Company