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Tacrolimus enhances colon anastomotic healing in rats
Author(s) -
Kiyama Teruo,
Tajiri Takashi,
Tokunaga Akira,
Yoshiyuki Toshiro,
Barbul Adrian
Publication year - 2002
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1046/j.1524-475x.2002.t01-1-10506.x
Subject(s) - tacrolimus , anastomosis , hydroxyproline , collagenase , medicine , wound healing , submucosa , pharmacology , urology , gastroenterology , surgery , chemistry , transplantation , biochemistry , enzyme
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 (µg 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. (WOUND REP REG 2002;10:308–313)