Insulin-like growth factor I and truncated keratinocyte growth factor accelerate healing of left-sided colonic anastomoses

Background: Human full-length keratinocyte growth factor (KGF) promotes hea ling of colon anastomoses in rats through mechanisms other than enhancement of collagen synthesis. Since insulinlike growth factor (IGF) I increases m atrix synthesis, the aim of this study was to evaluate the effect of system ic truncated KGF (tKGF), IGF-I and combined tKGF-IGF-I administration on th e healing of colonic anastomoses in rats. Methods: Rats underwent laparotomy, division of the left colon, and sigmoid osigmoidostomy. tKGF (1 mg/kg), IGF-I (1 mg/kg), tKGF-IGF-I (both 1 mg/kg) or vehicle was administered intraperitoneally in four groups (n = 18 per gr oup) 12 h before surgical intervention, and then once daily until killing ( six animals per group; 2, 4 and 6 days after surgery). Bursting pressure me asurements, histological evaluation, morphometric analysis, mucin and colla gen staining, and 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry of th e anastomotic site were undertaken. Results: Administration of tKGF, IGF-I and the combination of both growth f actors significantly increased anastomotic bursting pressure at postoperati ve day 2 (63, 71 and 113 per cent respectively), day 4 (68, 83 and 80 per c ent) and day 6 (48, 43 and 43 per cent) compared with the control group. No intergroup differences were found. Histological examination, mucin and Brd U staining, and measurement of colonic crypt depth indicated less inflammat ion, increased acidic mucin content, a higher crypt cell proliferation rate and thickened mucosal layer in the growth factor-treated animals than in c ontrols. Enhanced collagen staining was observed only in IGF-treated animal s. Conclusion: tKGF and IGF-I markedly accelerate the healing of colonic anast omoses in rats. However, combined administration of the two growth factors does not show additional benefit. Both growth factors may be acting to acce lerate host reparative processes as well as to enhance protection of the an astomotic wound bed.