Effects of perioperative treatment with TNP-470 on the resistance of colonic anastomoses in rats

Aims: The present study was designed to evaluate the effects of perioperati ve treatment with TNP-470 on the resistance of colonic anastomoses. TNP-470 is a drug that was developed as an inhibitor of angiogenesis. Methods: A c olonic anastomosis was constructed in Sprague-Dawley rats. From 4 days befo re surgery to 4 days afterwards, each animal received daily intraperitoneal treatment that differed according to the group to which it belonged: the c entral group, which received gum arabic, or the TNP group, which received 3 0 mg/kg TNP-470 in gum arabic. The size of the cecum and the diameters of t he pre-anastomotic and post-anastomotic colon were measured at operation an d 4 days after surgery, when all animals were sacrificed. At this time the presence of adhesions was also investigated. Each segment containing an ana stomosis was removed and the bursting pressure (BP) and bursting wall tensi on (BWT) were determined. Results: Loss of cecum caliber and decreases in p re-anastomotic diameter were significantly greater in the TNP group than in the control group (p = 0.017 and p = 0.004, respectively). Dilatation and obstruction of the colon were more frequent in the control group, but the d ifference between the groups was significant only with respect to dilatatio n (p = 0.005). Moreover, loss of body weight was greater in the TNP group t han in the control group (p < 0.001). BP and BWT were significantly lower i n animals that had received TNP-470 (p = 0.04 and p = 0.005, respectively). With respect to post-anastomotic diameter, general adhesions and adhesions to the anastomotic line, there were no statistically significant differenc es between the groups. Conclusions: Perioperative treatment with TNP-470, a n inhibitor of angiogenesis, affects the healing and reduces the resistance of colonic anastomoses. Copyright (C) 2000 S. Karger AG, Basel.