Effects of perioperative treatment with TNP-470 on the resistance of colonic anastomoses in rats.
OBJECTIVE
The present study was designed to evaluate the effects of perioperative 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 colonic anastomosis was constructed in Sprague-Dawley rats. From 4 days before surgery to 4 days afterwards, each animal received daily intraperitoneal treatment that differed according to the group to which it belonged: the control group, which received gum arabic, or the TNP group, which received 30 mg/kg TNP-470 in gum arabic. The size of the cecum and the diameters of the pre-anastomotic and post-anastomotic colon were measured at operation and 4 days after surgery, when all animals were sacrificed. At this time the presence of adhesions was also investigated. Each segment containing an anastomosis was removed and the bursting pressure (BP) and bursting wall tension (BWT) were determined.


RESULTS
Loss of cecum caliber and decreases in pre-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 difference between the groups was significant only with respect to dilatation (p = 0.005). Moreover, loss of body weight was greater in the TNP group than in the control group (p < 0.001). BP and BWT were significantly lower in 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 differences between the groups.


CONCLUSIONS
Perioperative treatment with TNP-470, an inhibitor of angiogenesis, affects the healing and reduces the resistance of colonic anastomoses.
García-Olmo
D C
DC
Experimental Surgery Unit, Albacete General Hospital, Albacete, Spain.
Payá
J
J
García-Olmo
D
D
D000714:Anastomosis, Surgical; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000818:Animals; D003106:Colon / Q000601:surgery; D003110:Colonic Neoplasms / Q000601:surgery*; D003510:Cyclohexanes; D005260:Female; D008297:Male; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D019990:Perioperative Care; D011446:Prospective Studies; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D014945:Wound Healing
D020533:Angiogenesis Inhibitors; D003510:Cyclohexanes; D012717:Sesquiterpenes; D000077609:O-(Chloroacetylcarbamoyl)fumagillol