A perivascular system releasing sirolimus prevented intimal hyperplasia in a rabbit model in a medium-term study

Int J Pharm. 2012 May 10;427(2):311-9. doi: 10.1016/j.ijpharm.2012.02.023. Epub 2012 Feb 21.

Abstract

The main complication of aortocoronary reconstruction with vein grafts is restenosis in the course of time. The aim was to assess the effect of a periadventitial polyester mesh releasing sirolimus on intimal hyperplasia of autologous grafts. We implanted v. jugularis ext. into a. carotis communis in rabbits. The vein graft was either intact, or was wrapped with a pure polyester mesh, or with a sirolimus-releasing mesh. Three and six weeks after surgery, the veins were subjected to standard histological staining and the thicknesses of the tunica intima, the media and the intima-media complex were measured. Wrapping the vein with a mesh releasing sirolimus or with a pure mesh decreased the thickness of the intima in comparison with a vein graft by 73 ± 11% or 73 ± 8% after 3 weeks, and by 73 ± 9% or 59 ± 12% after 6 weeks, respectively. Sirolimus-releasing meshes reduced the thickness of the media by 65 ± 9% and 20 ± 12% after 3 and 6 weeks. The thickness of the intima-media complex in grafts with sirolimus-releasing meshes decreased by 60 ± 6% and 30 ± 13% in comparison with pure PES meshes, after 3 and 6 weeks, respectively. A periadventitial polyester mesh releasing sirolimus has the potential to become an effective device in preventing vein graft restenosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Count
  • Cell Proliferation
  • Chinchilla
  • Drug Implants
  • Graft Occlusion, Vascular / pathology
  • Graft Occlusion, Vascular / prevention & control*
  • Hyperplasia / pathology
  • Immunohistochemistry
  • Immunosuppressive Agents / administration & dosage*
  • Immunosuppressive Agents / therapeutic use*
  • Male
  • Muscle, Smooth, Vascular / drug effects
  • Paraffin Embedding
  • Polyesters
  • Proliferating Cell Nuclear Antigen / metabolism
  • Rabbits
  • Sirolimus / administration & dosage*
  • Sirolimus / therapeutic use*
  • Surgical Mesh
  • Tissue Fixation
  • Tunica Intima / pathology*
  • Tunica Media / pathology
  • Veins / transplantation

Substances

  • Drug Implants
  • Immunosuppressive Agents
  • Polyesters
  • Proliferating Cell Nuclear Antigen
  • Sirolimus