The Effect of Celecoxib Administration on the Healing and Neovascularization of Colonic Anastomosis in Rats

Abstract

ABSTRACTBackground: The aim of this experimental study was to investigate whether the perioperative administration of the selective cyclooxygenase-2 inhibitor celecoxib affects the angiogenetic process and the healing of colonic anastomoses. Methods: Seventy-two male Wistar rats underwent colonic resection and anastomosis. Celecoxib (10 mg/kg/day—celecoxib group) or placebo (control group) was administered perioperatively. Rats of both groups were sacrificed on either the third or the seventh postoperative day and bursting pressures of the anastomoses were measured. Gelatine-degrading matrix metalloproteinases (MMPs) were identified with gelatine zymography, and proMMP-2 and vascular endothelial growth factor (VEGF) levels from both anastomotic site and tissue adjacent to the anastomosis were evaluated. Histologic evaluation of microvessels was performed by immunohistochemistry using an anti-CD34 monoclonal antibody. Results: Celecoxib did not significantly decrease anastomotic bursting pressures. Gelatin zymography revealed the presence of MMP-2, proMMP-2, and proMMP-9. MMP concentration was higher at the anastomotic tissue as compared with tissue distant to the anastomosis. Celecoxib resulted in a significant reduction in proMMP-2 levels at the anastomosis at both third and seventh postoperative day. VEGF levels from the anastomotic tissue were also found lower in the celecoxib group. Histological examination showed a celecoxib-induced reduction of newly formed CD34-stained vessels. Conclusions: Although the perioperative administration of celecoxib resulted in suppression of angiogenesis in the newly formed anastomoses, bursting pressures remained unaffected and subsequently safety was not compromised.