Intraperitoneal cytostatics impair early post-operative collagen synthesis in experimental intestinal anastomosesP6

Collagen synthesis in intestinal anastomoses has been measured in rats after in vivo administration of cytostatics. The cytostatics were administered during 5 consecutive days either intravenously or intraperitoneally. On day 3 of the course the rats received both an ileal and a colonic anastomosis. The animals were sacrificed 3 and 7 days after operation. The cytostatics regimen used was a combination of 5-fluorouracil, bleomycin and cisplatinum in a dose of 10, 2 and 0.35 mg kg-1 day-1, respectively. In an additional group, a twice higher dose was given intraperitoneally. Three days after operation a severe inhibition of the collagen synthesis was observed in all the cytostatics treated groups, both in ileum and in colon. The effects of intraperitoneal administration were much more pronounced than those observed after an equal dose given intravenously. Seven days after operation the collagen synthesis in the intravenously treated groups was restored to the level of the control group. However, in the intraperitoneal groups the collagen synthesis in ileal anastomoses was still inhibited. Thus, cytostatics suppress collagen synthesis in intestinal anastomoses. The effect is more severe after intraperitoneal than after intravenous administration, confirming our earlier hypothesis that the former mode of administration comprises a higher risk for anastomotic integrity.