Acid-base homeostasis parallels anabolism in surgically stressed rats treated with GH and IGF-I.

The effect of a standard surgical stress and subsequent total parenteral nutrition (TPN) treatment on systemic acid-base balance was assessed in four groups of rats: TPN controls, TPN coinfused with recombinant human insulin-like growth factor I (rhIGF-I, 800 micrograms/day), TPN with recombinant human growth hormone (rhGH, 800 micrograms in two divided daily sc doses), and combined rhGH plus rhIGF-I (800 + 800 micrograms/day). After the 6-day time course, TPN controls exhibited a systemic metabolic acidosis (HCO3- = 20.4 +/- 0.4 mM) and lost 7 g body wt/6 days. Either growth factor ameliorated the acidosis (rhGH = 22.6 +/- 0.6 and IGF-I = 22.0 +/- 0.5 mM) and promoted weight gain (11 +/- 2 and 10 +/- 3 g/6 days, respectively). Combined growth factor treatment, rhGH+rhIGF-I, restored acid-base balance (HCO3- = 24.7 +/- 0.6 mM) and exhibited an additive effect on weight gain (25 +/- 3 g/6 days). Ammonium and sulfate excretion as indexes of renal acid excretion and systemic sulfuric acid production, respectively, were highest in the TPN control, Growth factors alone reduced sulfuric acid production, whereas combined growth factor treatment reduced acid production and eliminated acid excretion despite elevated renal glutaminase activity. However, renal cortical glutamate content was elevated in the combined growth factor treatment (10.6 +/- 0.7 vs. 7.3 +/- 0.5 rhGH+rhIGF-1 vs. TPN, P < 0.05), consistent with repression of the elevated glutaminase activity. These findings point to an important role for acid-base homeostasis in the anabolic response and are consonant with an additive effect of growth factors, rhGH+rhIGF-I, in correcting the metabolic acidosis associated with surgical stress.