4.7 Article

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

Journal

INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 427, Issue 2, Pages 311-319

Publisher

ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijpharm.2012.02.023

Keywords

Sirolimus; Perivascular wrap; Controlled drug release; Autologous vein; Intimal hyperplasia

Funding

  1. Grant Agency of the Ministry of Health of the CR [NR9358]
  2. Centre for Cardiovascular Research [1M6798582302]
  3. Czech Science Foundation [102/08/0691, P108/11/0794]
  4. [AV0Z50110509]

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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. (C) 2012 Elsevier B.V. All rights reserved.

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