title: Tacrolimus enhances colon anastomotic healing in rats.
abstract: 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.
authors.affiliation: Department of Surgery I, Nippon Medical School, Tokyo, Japan. kiyama@nms.ac.jp
authors.forename: Teruo
authors.initials: T
authors.lastname: Kiyama
authors.forename: Takashi
authors.initials: T
authors.lastname: Tajiri
authors.forename: Akira
authors.initials: A
authors.lastname: Tokunaga
authors.forename: Toshiro
authors.initials: T
authors.lastname: Yoshiyuki
authors.forename: Adrian
authors.initials: A
authors.lastname: Barbul
mesh_terms: D000714:Anastomosis, Surgical; D000818:Animals; D017364:Collagenases / Q000378:metabolism; D003106:Colon / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D006909:Hydroxyproline / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D016559:Tacrolimus / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D007166:Immunosuppressive Agents; D017364:Collagenases; D006909:Hydroxyproline; D016559:Tacrolimus