Effects of mTOR Inhibitors in Prevention of Abdominal Adhesions

ABSTRACT

Purpose of the Study: 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. Materials and Methods: 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. Results: 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. Conclusions: Everolimus effectively reduced adhesions. Nevertheless, it also reduced wound tensile strength: an effect which seemed to be due to inhibition of fibroblast proliferation.

Keywords::

• Sirolimus
• Everolimus
• mTOR
• adhesion
• abdominal
• wound

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