A NITROGEN-FREE HYPOCALORIC DIET AND RECOMBINANT HUMAN GROWTH-HORMONESTIMULATE POSTOPERATIVE PROTEIN-SYNTHESIS - FASTED AND FED LEUCINE KINETICS IN THE SURGICAL PATIENT

Twelve otherwise healthy patients undergoing elective surgery for rese ction of rectosigmoid adenocarcinoma were randomly allocated to two gr oups: one group receiving intravenous dextrose 5% 600 to 800 kcal.d(-1 ) (DX, n = 6) and the other group receiving the same amount of dextros e intravenously plus recombinant human growth hormone (DX + rGH, n = 6 ), Supplementation with rGH started on the day of surgery and continue d postoperatively for 5 days, No nitrogen was provided in the diet. Th is regimen was started 3 days before surgery and continued for 5 days after surgery. Protein kinetics were studied over a period of 8 hours in all patients, Following an overnight fast, a primed constant infusi on of L-[1-C-13]leucine was maintained for 4 hours (fasted state) and continued for a further 4 hours (fed state) during which 5% beet dextr ose (low C-13 content) with or without rGH was administered. The isoto pe studies were performed on the day before surgery and 6 days after s urgery. Other measurements included urinary nitrogen excretion, gaseou s exchange, and plasma concentrations of insulin, GH, and insulin-like growth factor-I (IGF-I). Addition of rGH to the dextrose diet had a s ignificant positive effect on protein synthesis (P =.02), Surgery was responsible for a significant increase in postoperative whole-body pro tein breakdown and synthesis and leucine oxidation (P <.01), although lesser changes were observed in the DX group. An interaction between r GH and surgery was associated with a significant increase in protein s ynthesis (P =.009), but not with changes in either protein breakdown o r leucine oxidation. Carbohydrate provision in the form of beet dextro se during the fed state of the isotopic study did not attenuate the si gnificant decrease in protein synthesis (P =.01) or breakdown (P =,003 ) either before or after surgery, probably reflecting the absence of n itrogen in the diet. No significant interaction was found between rGH and feeding. These results of leucine kinetics indicate that addition of rGH to a low-dextrose intake in the absence of dietary nitrogen can actually promote protein synthesis, The low levels of leucine oxidati on could be explained by the fact that amino acids resulting from prot ein degradation were directed preferentially toward resynthesis of new proteins rather than to oxidative pathways. There was a significant i ncrease in plasma insulin and GH in the group receiving rGH (P <,05), The postoperative plasma concentration of IGF-I did not change in the latter group compared with the DX group, in which IGF I concentration decreased significantly (P <.05) as part of the response to combined s urgery and dietary restriction. Although both IGF-I and insulin are in dependently capable of stimulating protein synthesis, elevated levels of either hormone or GH itself may primarily modulate protein synthesi s, even with a low intake of carbohydrates. Copyright (C) 1997 by W.B. Saunders Company.