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J Am Coll Cardiol, 1998; 32:1109-1117
© 1998 by the American College of Cardiology Foundation
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EXPERIMENTAL STUDIES

Long-term endothelial dysfunction is more pronounced after stenting than after balloon angioplasty in porcine coronary arteries

Heleen M. M. van Beusekom, PhD* b, Deirdre M. Whelan, BSc* b, Sjoerd H. Hofma, MD* b, Stefan C. Krabbendam, BSc* b, Victor W. M. van Hinsbergh, PhD* {dagger} b,d, Pieter D. Verdouw, PhD* b and Willem J. van der Giessen, MD, PhD* b

* Experimental Cardiology, Thoraxcenter, Cardiovascular Research Institute COEUR, Erasmus University Rotterdam, Rotterdam, The Netherlands
b Interuniversity Cardiology Institute ICIN, Rotterdam, The Netherlands
{dagger} Gaubius Laboratory TNO-PG, Leiden, The Netherlands
d Institute for Cardiovascular Research, Free University, Amsterdam, The Netherlands

Manuscript received April 17, 1998; revised manuscript received June 1, 1998, accepted June 12, 1998.

Address for correspondence: Heleen M.M. van Beusekom, PhD, Dept. of Cardiology, Thoraxcenter, Ee 2357, Erasmus University Rotterdam, PO Box 1738, 3000 DR Rotterdam, The Netherlands
vanbeusekom{at}tch.fgg.eur.nl

Objectives. To compare percutaneous transluminal coronary angioplasty (PTCA) and stent implantation with respect to the long-term changes they induce in the newly formed endothelium in porcine coronary arteries by studying both morphological and functional parameters of the endothelium at 2 weeks and 3 months after intervention.

Background. Problems affecting PTCA or stent implantation have been overcome to a large extent by means of better techniques and the availability of new drugs. Late problems, however, still exist in that restenosis affects a large number of patients. With an increasing number of patients being treated with stents, the problem of in-stent restenosis is of even greater concern, as this seems difficult to treat. A functional endothelial lining is thought to be important in controlling the growth of the underlying vascular tissue. We hypothesized that the enhanced neointimal hyperplasia observed after stenting is associated with a more pronounced and prolonged endothelial dysfunction.

Methods. Arteries were analyzed using a dye-exclusion test and planimetry of permeable areas. Thereafter, the arteries were processed for light and scanning electron microscopy for assessment of morphology and proliferative response.

Results. Leakage of the endothelium for molecules such as Evans blue-albumin as well as prolonged endothelial proliferation is observed as late as 3 months after the intervention, and is more pronounced after stenting. Permeability is associated with distinct morphologic characteristics: endothelial retraction, the expression of surface folds, and the adhesion of leukocytes.

Conclusions. Stenting especially decreases long-term vascular integrity with respect to permeability and endothelial proliferation, and is associated with distinct morphologic characteristics.

Abbreviations and Acronyms
  BrdU = bromodeoxy uridine
  EB = Evans blue
  EM = electron microscopy
  LM = light microscopy
  NI = neointimal thickening
  PTCA = percutaneous transluminal coronary angioplasty




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