Endothelial function rather than endothelial restoration is altered in paclitaxel- as compared to bare metal-, sirolimusand tacrolimus-eluting stents

EuroIntervention. 2010 May;6(1):117-25.

Abstract

Aims: Drug eluting stents (DES) are under scrutiny for late stent thrombosis. Impaired re-endothelialisation is proposed as an explanation but coronary and peripheral-artery models disagree. We assessed physical and functional endothelial restoration within bare (BMS), paclitaxel, sirolimus and tacrolimus eluting stents and the distal microvasculature in porcine coronary arteries.

Methods and results: Endothelium within and distal to DES and BMS was assessed for stent-strut endothelial-restoration (five days) and endothelial-function (five, 28 days, by eNOS and vWF expression) and by in vitro microvascular function. There were no significant differences (P=0.3) in stent strut endothelial-restoration at five days between DES (76-90%) and BMS (95%). However, the microvasculature distal to PES showed a decreased NO bioavailability at five days, which improved at 28 days. Within the stent, however, PES still showed a reduced eNOS expression at 28 days (P</=0.002).

Conclusions: DES in porcine coronary arteries show no significant early differences in re-endothelialisation as compared to BMS. However, PES did affect endothelial function both within and distal to stents. These results extend the concept of delayed healing in DES to include delayed restoration of function rather than endothelial presence as a possible explanation for late unwanted sequelae. Microvascular dysfunction does not predict in-stent delayed endothelialisation in this model.

Publication types

  • Comparative Study

MeSH terms

  • Angioplasty, Balloon, Coronary / adverse effects
  • Angioplasty, Balloon, Coronary / instrumentation*
  • Animals
  • Cardiovascular Agents / administration & dosage*
  • Cell Proliferation / drug effects
  • Coronary Angiography
  • Coronary Circulation / drug effects
  • Coronary Vessels / drug effects*
  • Coronary Vessels / metabolism
  • Coronary Vessels / pathology
  • Coronary Vessels / physiopathology
  • Dose-Response Relationship, Drug
  • Drug-Eluting Stents*
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / pathology
  • Endothelium, Vascular / physiopathology
  • Immunohistochemistry
  • Metals*
  • Microcirculation / drug effects
  • Microscopy, Electron, Scanning
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type III / metabolism
  • Paclitaxel / administration & dosage*
  • Sirolimus / administration & dosage*
  • Stents*
  • Swine
  • Tacrolimus / administration & dosage*
  • Time Factors
  • Vasodilation / drug effects
  • Vasodilator Agents / pharmacology
  • von Willebrand Factor / metabolism

Substances

  • Cardiovascular Agents
  • Metals
  • Vasodilator Agents
  • von Willebrand Factor
  • Nitric Oxide
  • Nitric Oxide Synthase Type III
  • Paclitaxel
  • Sirolimus
  • Tacrolimus