THE EFFECT OF 5-FLUOROURACIL ON WOUND-HEALING AND COLLAGEN-SYNTHESIS IN LEFT COLON ANASTOMOSES - AN EXPERIMENTAL-STUDY IN THE RAT

In an experimental study resembling clinical use of adjuvant 5-fluorou racil (5-FU) treatment of colorectal carcinoma 86 male Wistar rats wer e operated with a standardized left colon resection and anastomosis wi th interrupted sutures. Treatment was given as daily intraperitoneal ( i.p.) injections. The animals were randomized to one of two groups: (A ) 5-FU (20 mg/kg) i.p., and (B) NaCl i.p. from the day of operation to sacrifice. Anastomotic complications were registered. In experiment 1 animals were randomized within treatment groups to be tested for anas tomotic breaking strength with or without sutures in place when sacrif iced 7 days postoperatively. In experiment 2 collagen synthesis was st udied by an in vivo incorporation and hydroxylation of H-3-proline in the anastomotic segment during 24 h prior to sacrifice. The animals we re sacrificed in groups on the third or seventh postoperative day. A h igher number of anastomotic complications was registered when 5-FU was given. The anastomotic breaking strength was only 40% of controls bot h when tested with and without sutures. A reduced radioactivity of H-3 -hydroxyproline in the anastomotic segment after 7 days of 5-FU treatm ent was found implying a reduction in collagen synthesis. In our model colonic healing was impaired after i.p. 5-FU treatment and this could be attributed to a reduced collagen synthesis in the wound gap as wel l as in the adjacent tissue responsible for the suture-holding capacit y.