Copyright © 2005, European Society of Cardiology
Histopathologic alterations following local delivery of dexamethasone to inhibit restenosis in murine arteries
aTNO-Quality of Life, Gaubius Laboratory, Zernikedreef 9, 2333 CK Leiden, The Netherlands
bDepartment of Cardiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
cDepartment of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
dDepartment of General Internal Medicine, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
* Corresponding author. Department of Cardiology, C5-P, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands. Tel.: +31 71 526 6695; fax: +31 71 526 6886. Email address: j.w.jukema{at}lumc.nl
Objective: Dexamethasone-eluting stents are currently under evaluation to prevent post-angioplasty restenosis. The efficacy and safety of dexamethasone as an anti-restenotic agent is still unclear. We assess the effect of perivascular delivery of dexamethasone on vascular pathology in a mouse model of restenosis.
Methods and results: In this study we investigate the ability of both systemic and local dexamethasone treatment to inhibit neointima formation after cuff placement around C57BL/6 mouse femoral artery. As in the clinical situation, systemic dexamethasone treatment shows adverse side effects in animals, including weight loss. In contrast, local delivery of dexamethasone using a drug-eluting polymer cuff inhibits neointima formation and has no systemic adverse effects. Pathobiological examination of the experimental arteries, however, reveals a dose-dependent medial atrophy, a reduction in vascular smooth muscle cells and collagen content, an increase in apoptotic cell count and disruption of the internal elastic lamina.
Conclusions: Our results demonstrate that although local dexamethasone delivery is effective as an inhibitor for neointima formation, it is dose-dependently associated with adverse vascular morphological changes pointing to a loss of vascular integrity.
KEYWORDS Arteries; Histo(patho)logy; Restenosis; Smooth muscle; Stents; Animal models
Time for primary review 18 days
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