title: Effects of mTOR Inhibitors in Prevention of Abdominal Adhesions.
abstract: Postsurgical adhesions can occur after laparotomy and can cause morbidity. Local delivery of sirolimus prevented adhesion formation in various experiments. We analyzed the impact of orally dosed mammalian target of rapamycin inhibitors on abdominal adhesion formation and wound tensile strength in an experimental model.
  
  
  
  Wistar albino rats were divided into sirolimus, everolimus, and control groups (n = 6 per group). Experimental animals underwent midline laparotomy and adhesion induction procedure which included cecum abrasion and mesh implantation. Animals were administered oral sirolimus (4 mg/kg), everolimus (3 mg/kg), or placebo starting on postoperative day 1. Treatments were given until postoperative day 7. At postoperative day 21, adhesions were scored. Meshes were resected with the attached abdominal wall and cecal segment and stained with Sirius red for collagen density analysis. Midline scars were excised for tensile strength measurement. Effects of sirolimus and everolimus on fibroblast proliferation were also assessed.
  
  
  
  Mean adhesion score of the everolimus group (7.83 ± 1.17) was significantly lower compared to sirolimus (11.00 ± 0.63) and control (11.66 ± 0.51) groups. Mean collagen density of the everolimus group (33.5 ± 7.8) was significantly lower compared to sirolimus (50.7 ± 9.69) and control (53.8 ± 12.4) groups. Mean tensile strength of the control group (26.41 ± 2.10) was significantly higher compared to sirolimus (17.89 ± 1.9) and everolimus (21.37 ± 1.25) groups. It was significantly lower in sirolimus group than everolimus group. Both sirolimus and everolimus treated media inhibited fibroblast proliferation significantly compared to media alone.
  
  
  
  Everolimus effectively reduced adhesions. Nevertheless, it also reduced wound tensile strength: an effect which seemed to be due to inhibition of fibroblast proliferation.
authors.affiliation: a Department of Surgery, Queen Elizabeth II Health Sciences Centre , Dalhousie University , Halifax , Nova Scotia , Canada.
authors.forename: Sanem
authors.initials: S
authors.lastname: Guler
authors.affiliation: b Atlantic Centre for Transplantation Research , Dalhousie University , Halifax , Nova Scotia , Canada.
authors.forename: Sertac
authors.initials: S
authors.lastname: Cimen
authors.affiliation: b Atlantic Centre for Transplantation Research , Dalhousie University , Halifax , Nova Scotia , Canada.
authors.forename: Qianni
authors.initials: Q
authors.lastname: Hu
authors.affiliation: b Atlantic Centre for Transplantation Research , Dalhousie University , Halifax , Nova Scotia , Canada.
authors.forename: Ananda Baskaran
authors.initials: AB
authors.lastname: Venkatachalam
authors.forename: Michael
authors.initials: M
authors.lastname: Hart-Matyas
authors.affiliation: a Department of Surgery, Queen Elizabeth II Health Sciences Centre , Dalhousie University , Halifax , Nova Scotia , Canada.
authors.forename: Ian
authors.initials: I
authors.lastname: Alwayn
mesh_terms: D016475:3T3 Cells; D000005:Abdomen / Q000601:surgery*; D000284:Administration, Oral; D000818:Animals; D002432:Cecum / Q000187:drug effects / Q000293:injuries / Q000601:surgery; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D000068338:Everolimus / Q000008:administration & dosage; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D008297:Male; D051379:Mice; D051381:Rats; D017208:Rats, Wistar; D020123:Sirolimus / Q000008:administration & dosage; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D013718:Tensile Strength / Q000187:drug effects; D000267:Tissue Adhesions / Q000517:prevention & control*; D014947:Wounds and Injuries / Q000503:physiopathology
chemical_list: D007166:Immunosuppressive Agents; D003094:Collagen; D000068338:Everolimus; C546845:mTOR protein, rat; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus
keywords: Everolimus; Sirolimus; abdominal; adhesion; mTOR; wound