title: The effects of tacrolimus on colonic anastomotic healing in rats.
abstract: OBJECTIVE
  The aim of this experimental study is to investigate the effects of tacrolimus on colonic anastomotic healing after subcutaneous administration.
  
  
  METHODS
  Forty Albino-Wistar male rats were divided into two groups, with two equal subgroups each. They all underwent colonic resection followed by a single-layer, inverted colon anastomosis and were injected subcutaneously with either 1 ml of 0.9% NaCl solution or tacrolimus (0.1 mg/kg body weight) depending on their group. Half of the rats were sacrificed on the fourth postoperative day, while the remaining half were sacrificed on the eighth postoperative day. Macroscopical and histological assessment was performed, while anastomotic bursting pressures and the tissue concentrations in hydroxyproline and collagenase I were evaluated.
  
  
  RESULTS
  On the fourth postoperative day, the bursting pressures (217.00 ± 11.12, p < 0.001), the fibroblast activity (2.80 ± 0.42, p = 0.022), the neoangiogenesis (2.10 ± 0.32, p = 0.007) and the tissue hydroxyproline concentration (254.23 ± 67.10, p = 0.001) were significantly higher in the tacrolimus-treated animals. Furthermore, tacrolimus significantly decreased the inflammatory cell infiltration (1.50 ± 0.53, p < 0.001) and the tissue collagenase I concentration (4.16 ± 0.76, p = 0.002). On the eighth day, the bursting pressure (264.00 ± 32.61, p < 0.001) and the hydroxyproline tissue concentration (331.04 ± 55.56, p = 0.002) were significantly higher in the tacrolimus subgroups. The inflammatory cell infiltration (1.20 ± 0.42, p < 0.001) and the collagenase I concentration (1.61 ± 0.83, p < 0.001) were significantly lower. In addition, the adhesion formation score was significantly lower (1.20 ± 0.92, p = 0.065).
  
  
  CONCLUSIONS
  Tacrolimus, when injected subcutaneously, promotes healing of colonic anastomoses in rats. It impairs not only inflammatory response but also collagen degradation, resulting to increased anastomotic strength on the fourth as well as on the eighth postoperative day.
authors: 4th Surgical Department, Aristotle University of Thessaloniki, Thessaloniki, Greece. draptis@hotmail.com
authors: D
authors: D
authors: Raptis
authors: I
authors: I
authors: Mantzoros
authors: M G
authors: MG
authors: Pramateftakis
authors: K
authors: K
authors: Despoudi
authors: T
authors: T
authors: Zaraboukas
authors: G
authors: G
authors: Koliakos
authors: I
authors: I
authors: Kanellos
authors: Ch
authors: Ch
authors: Lazarides
mesh_terms: D000714:Anastomosis, Surgical; D000818:Animals; D017364:Collagenases / Q000187:drug effects / Q000378:metabolism; D003106:Colon / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D006909:Hydroxyproline / Q000187:drug effects / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D011312:Pressure / Q000009:adverse effects; D051381:Rats; D017208:Rats, Wistar; D012421:Rupture / Q000209:etiology; D016559:Tacrolimus / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D007166:Immunosuppressive Agents; D017364:Collagenases; C417249:collagenase 1; D006909:Hydroxyproline; D016559:Tacrolimus