Endothelialization of sirolimus-eluting stents with slow and extended drug release in the porcine overstretch model

J Invasive Cardiol. 2008 Dec;20(12):631-4.

Abstract

Background: Vascular healing of intracoronary stents has been shown to be delayed in drug-eluting stents (DES) due to the cytotoxic compounds on the stent surface that prevent stent ingrowth and endothelialization. The lack of endothelialization explains the occurrence of late and very late stent thrombosis in DES.

Materials and methods: In 11 house swines (body weight 38-45 kg), 3 stents were implanted randomly into the 3 large epicardial coronary arteries, namely a bare-metal stent (BMS), a sirolimus-eluting stent with slow-release (SES) and a SES with extended-release (SESXR). Stent length was 18 mm, and stent diameter 3 mm. All stents were of identical design. Animals were followed for 3 (n = 3), 7 (n = 4) and 14 (n = 4) days, respectively. One animal died before implantation due to hyperthermia. On the day of explantation, the animals were euthanized and endothelialization was tested by scanning electron microscopy after drying and sputtering the samples. Endothelial coverage was determined semiquantitatively by 2 observers.

Results: Endothelialization was more rapid with BMS and SESXR than SES at 3 and 14 days. At 7 days there were no significant differences between the 2 SES.

Conclusions: Endothelialization of intracoronary stents is faster with BMS and SESXR at 3 days than with SES. These differences persist at 14 days, suggesting delayed vascular healing with the slow-release SES.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Coronary Restenosis / chemically induced*
  • Coronary Restenosis / pathology
  • Coronary Vessels / drug effects
  • Coronary Vessels / pathology
  • Delayed-Action Preparations
  • Disease Models, Animal
  • Drug-Eluting Stents*
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / pathology*
  • Immunosuppressive Agents / pharmacokinetics
  • Immunosuppressive Agents / toxicity*
  • Metals
  • Sirolimus / pharmacokinetics
  • Sirolimus / toxicity*
  • Stents
  • Swine
  • Wound Healing / drug effects

Substances

  • Delayed-Action Preparations
  • Immunosuppressive Agents
  • Metals
  • Sirolimus