Histopathologic alterations following local delivery of dexamethasone to inhibit restenosis in murine arteries.
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.


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.
Pires
Nuno M M
NM
TNO-Quality of Life, Gaubius Laboratory, Zernikedreef 9, 2333 CK Leiden, The Netherlands.
Schepers
Abbey
A
van der Hoeven
Barend L
BL
de Vries
Margreet R
MR
Boesten
Lianne S M
LS
Jukema
J Wouter
JW
Quax
Paul H A
PH
D015906:Angioplasty, Balloon, Coronary; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000032:analysis; D003327:Coronary Disease / Q000628:therapy; D023903:Coronary Restenosis / Q000517:prevention & control*; D003907:Dexamethasone / Q000008:administration & dosage* / Q000627:therapeutic use; D005263:Femoral Artery / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D015607:Stents; D017539:Tunica Intima / Q000473:pathology*
D000893:Anti-Inflammatory Agents; D003907:Dexamethasone; D003094:Collagen