The effect of tacrolimus on colon anastomotic healing

We have shown that the immunosuppressant tacrolimus (TA), used in solid organ transplantation, decreases wound mechanical strength and collagen deposition in dermal wound healing~ Failure of colonic healing has a major impact on surgical morbidity and mortality. Whether tacrolimus affects the outcome of colonic healing, however, is not known. We, therefore, studied the effect of systemic treatment with tacrolimus on standard parameters of colonic wound healing in rats. Groups of eight Sprague Dawley rats underwent laparotomy and single layer 6-0 prolene inverted left colon anastomosis. Beginning at the day of wounding, rats were treated once daily by s.c. injections with 2.0, or 5.0 mg TA/kg. Rats were sacrificed at postoperative day five for determination of colonic bursting pressure (BP) and hydroxyproline content of anastomoses (OHP), an index of reparative collagen deposition. Splenic lymphocytes were tested for proliferative activity (3H-thymidine uptake ). Tacrolimus levels in blood, obtained by cardiac puncture at the day of sacrific e, were measured by ELISA.