EPIDERMAL GROWTH-FACTOR AUGMENTS ADAPTATION FOLLOWING SMALL-BOWEL RESECTION - OPTIMAL DOSAGE, ROUTE, AND TIMING OF ADMINISTRATION

Background. In assorted animal models of small bowel resection (SBR), exogenous epidermal growth factor (EGF) has been shown to augment inte stinal adaptation. This study was designed to elucidate the optimal do se, route, and timing of exogenous EGF to boost adaptation in our muri ne model of SBR. Methods. Male ICR mice underwent either 50% proximal SBR or sham surgery (bowel transection with reanastomosis) and then ra ndomized to receive either saline or human recombinant EGF (5, 50, 150 , or 300 mu g/kg/day) by twice daily intraperitoneal (i.p.) injection or orogastric gavage (o.g.). At 7 days, protein and DNA content, crypt depth, and villus height were determined in the ileum. The premium do se and route was then given for 1 week either during (1 week after SBR ) or after the adaptive phase (1 month after SBR). Differences between group means were analyzed using ANOVA. A P < 0.05 was considered sign ificant. Results. EGF enhanced DNA and protein content, crypt depth, a nd villus height to the greatest extent at a dosage of 50 mu g/kg/day by the o.g. route. EGF had no significant effect on enhancing adaptati on when given after the adaptive response had already occurred. Conclu sions. Intestinal adaptation is optimally enhanced by a specific dose and route of EGF. Exogenous EGF enhances adaptation only during the ad aptive response to SBR and not after it has already taken place. Deter mination of the best circumstances for EGF administration will permit a systematic approach toward understanding a mechanism for the benefic ial effect of EGF during intestinal adaptation. (C) 1998 Academic Pres s.