Tacrolimus enhances colon anastomotic healing in rats

Tacrolimus inhibits T-cell function and neutrophil chemotaxis during inflammation. We hypothesized that tacrolimus would enhance healing of a rat colon anastomosis by reducing the inflammatory response. Fifty-five male Sprague Dawley rats, 230-260 g body weight, underwent identical surgical manipulation consisting of a single-layer, inverted colon anastomosis and the implantation of osmotic pumps subcutaneously in the left flank area. The animals were randomly assigned to receive tacrolimus, at a dose of 0.01, 0.1, or 1.0 mg/kg/day, or only the control solvent solution. The animals were euthanized 4 days after surgery. Colon-bursting pressure (mmHg), anastomotic collagen content ( micro g hydroxyproline/mg wet tissue), and anastomotic type IV collagenase activity (mU/mg protein) were measured. Tacrolimus significantly increased colon-bursting pressure at all doses used (146 +/- 9, 158 +/- 10, 151 +/- 6 mmHg; 0.01, 0.1, and 1.0 mg/kg/day, respectively) vs. control (119 +/- 7 mmHg, p < 0.01). There was no effect on collagen accumulation except at a dose of 0.01 mg/kg/day, which significantly decreased anastomotic collagen content (p < 0.05). Tacrolimus at a dose of 0.01 mg/kg/day increased anastomotic collagenase activity, which was not changed by treatment with the higher doses. Microscopic examination revealed the preservation of the multilayered structure, including the mucosal muscle, a thickened submucosa, and the proper muscle of the anastomotic site in the tacrolimus-treated groups. These data suggest that tacrolimus enhances wound strength during acute anastomotic healing despite a reduction in collagen content.