Effects of oral prednisone after stenting in a rabbit model of established atherosclerosis.
OBJECTIVE
The aim of this study was to compare the effects of systemic prednisone in combination with a bare-metal stent (BMS) or a paclitaxel-eluting stent (Taxus, Boston Scientific Corp., Natick, Massachusetts) on neointimal inhibition and vessel healing in an atherosclerotic rabbit model.


BACKGROUND
Inflammation plays a critical role in neointimal formation after coronary artery stenting. The efficacy of immunosuppressive doses of oral prednisone to inhibit in-stent neointimal proliferation was compared with BMS and with a commercially available paclitaxel-eluting stent (Taxus) in a rabbit model of established atherosclerosis.


METHODS
Bilateral iliac artery injury in atherosclerotic New Zealand White rabbits fed an atherogenic diet was followed by stent implantation. Animals randomly received Taxus stents, BMS (Express, Boston Scientific Corp.) and placebo, or BMS and oral prednisone (2.1 mg/kg/day for the first 7 days, followed by 1.4 mg/kg/day for 14 days and 0.7 mg/kg/day for 21 days). Stented arterial segments were harvested at 42 days and processed for light microscopy, immunohistochemistry, and organoid culture.


RESULTS
Compared with control subjects, prednisone-treated animals showed a 30% reduction in percent stenosis (p = 0.009), a 35% decrease in neointimal area (p < 0.003), and a 66% decrement in neointimal thickness (p < 0.001). Taxus stents also reduced all 3 parameters significantly (-34%, -39%, and -83%, respectively), but showed significantly more inflammatory cells and fibrin deposition and less endothelialization compared with the other 2 groups. Plaque burden was equal among groups, as shown by the identical stent and vessel area, and no remodeling was observed.


CONCLUSIONS
Systemic prednisone treatment and Taxus stents reduce neointimal formation compared with BMS. The extent of neointimal reduction is similar between prednisone- and Taxus stent-treated animals; however, Taxus stents resulted in a significantly greater delay in healing. Targeting of inflammatory pathways after percutaneous coronary intervention may be an efficacious way to prevent restenosis without the long-term risk of late thrombosis.
Ribichini
Flavio
F
Division of Cardiology of the Università di Verona, Ospedale Civile Maggiore, Verona, Italy.
Joner
Michael
M
Ferrero
Valeria
V
Finn
Aloke V
AV
Crimins
Johanna
J
Nakazawa
Gaku
G
Acampado
Eduardo
E
Kolodgie
Frank D
FD
Vassanelli
Corrado
C
Virmani
Renu
R
D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001011:Aorta / Q000166:cytology / Q000187:drug effects; D050197:Atherosclerosis / Q000473:pathology / Q000628:therapy*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D005938:Glucocorticoids / Q000627:therapeutic use; D007083:Iliac Artery / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects; D011241:Prednisone / Q000494:pharmacology / Q000627:therapeutic use*; D011817:Rabbits; D015607:Stents
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D011241:Prednisone