DOSE-DEPENDENT EFFECT OF OCTREOTIDE ON NITROGEN-RETENTION AND GLUCOSE-HOMEOSTASIS IN RESPONSE TO ENDOTOXEMIA IN PARENTERALLY FED RATS

Objective: This study compared the effect of different doses of octreo tide on glucose and protein homeostasis in rats receiving concomitant lipopolysaccharide and parenteral nutrition infusions. Methods: Sixty- six male Sprague Dawley rats (185 to 220 g) were randomized to receive parenteral nutrition only (PN), PN plus continuous infusion of Escher ichia coli 026:B6 lipopolysaccharide at 6 mg/kg/day (LPS), PN plus LPS plus octreotide at 10 mu g/kg/day (LPS + Oct 10), 100 mu g/kg/day (LP S + Oct 100), or 1000 mu g/kg/day (LPS + Oct 1000) for 48 hours. Prior to randomization all animals received isocaloric and isonitrogenous P N (170 kcal/kg/day as glucose and 1.1 g N/kg/day) and were kept nil pe r os except for water ad libitum. Nitrogen balance, urinary 3-methylhi stidine/creatinine ratio, serum glucose concentration, and incidence o f glycosuria were compared between groups. Serum urea nitrogen (SUN) c hanges were incorporated into the cumulative 48 hour nitrogen balance. ANOVA, Duncan's multiple range test, and Fisher's Exact Test were use d for statistical analysis. Results: Nitrogen balance (mg/48 hours) wa s significantly lower in all four groups receiving LPS +/- Oct when co mpared to the control group receiving PN alone. SUN (mg/dL) was signif icantly higher in all four groups receiving LPS +/- Oct when compared to control. There were no statistically significant differences in nit rogen balance or SUN among the four groups receiving LPS +/- Oct. The ratio of urinary 3-methylhistidine/creatinine was significantly higher in the LPS + Oct 1000 group compared to the PN group (0.77 +/- 0.37 v s. 0.42 +/- 0.24, p < 0.05). Serum glucose concentrations and incidenc e of glycosuria among the five groups were not significantly different . Conclusions: Endotoxin significantly reduces nitrogen balance compar ed to controls fed PN. Octreotide does not significantly improve nitro gen retention or glucose homeostasis in endotoxemic parenterally fed r ats.