Effect of Alprostadil on Colorectal Anastomoses Under Relative Ischemia

Anastomotic leak after colorectal surgery, which remains a serious clinical problem that causes augmented morbidity and mortality, is usually favored by ischemia. The aim of this study was to determine whether alprostadil may improve anastomotic wound healing under ischemic condition. Ninety-three adult Wistar rats were randomized into three groups: control, ischemia (by devascularization along the first 2 cm at each anastomotic end), and ischemia plus alprostadil. Resection of a colonic segment at the colorectal junction and an anastomosis was performed. Animals were euthanized at 8 d. Surgical site infection, anastomotic leak, and grade of intra-abdominal adhesions using a validated scale were determined. Bursting pressure and tension were calculated and histologic examination of the anastomosis was performed. The ischemic group revealed an increased anastomotic leak rate (14/31 versus 3/31) and a lower bursting pressure and tension when compared to control group, validating therefore the experimental model. After intraperitoneal injection of alprostadil, anastomotic leak rate was significantly lower (5/31) and the bursting pressure and tension were significantly increased. Histologic examination revealed a lower presence of inflammatory cells, and a significantly higher neovascularization and a higher presence of fibroblasts in treated animals when compared with the ischemic group. Alprostadil may have a positive effect on colonic anastomotic wound healing under relative ischemic condition. Alprostadil administration increases anastomotic bursting pressure, decreases leak rate, and reverses most of the histological changes caused by blood flow decrease. These protective effects could be caused by vasodilation, stimulation of neovascularization, and immunomodulatory properties.