Korean J Med.  1999 Jun;56(6):691-700.

The Effects of Local Endothelin Receptor Blocker Delivery on Porcine Coronary Stent Restenosis

• Jeong MH
• Kim W
• Kim YR
• Cho JH
• Kim JW
• Kim JH
• Kim SH
• Ahn YK
• Park JH
• Cho JG
• Park CS
• Park JC
• Kang JC

Abstract

OBJECTIVES
Coronary stent is one of the most effective currently available devices in the treatment of coronary artery diseases. But, coronary stent restenosis is one of major limitations in clinical stenting. Local drug delivery may be a new strategy for the prevention of stent restenosis. Endothelin receptor blocker is known to have vasodilatory and antiproliferative activities. To investigate the effects of local endothelin receptor blocker delivery on stent restenosis, local delivery was performed in the porcine model of coronary stent restenosis.
METHODS
Stent overdilation injury alone was performed in the control porcine coronary arteries (n=4, group A) and local delivery of endothelin receptor blocker prior to stenting was performed in the porcine coronary artery (n=9, group B). Endothelin receptor blocker (TAK-044, Takeda, Japan) was delivered at a rate of 1 ml/min (50 mg/10 ml) using the Dispatch Catheter. Follow-up quantitative coronary angiogram (QCA) and immunohistopathologic assessment were performed 4 weeks after stenting.
RESULTS
1) On QCA, percent diameter stenosis was significantly higher in Group A than in Group B (29.4+/-6.1 % vs. 14.5+/-11.6%, p<0.05). 2) Area stenosis was higher in Group A than in Group B (63.5+/-23.2 % vs. 40.9+/-13.3 %) measured by histopathologic method (p<0.05). 3) Neointimal area was higher in Group A than in Group B (3.53+/-1.9 mm2 vs. 1.75+/-0.8 mm2, p=0.03). 4) By immunocytochemistry, proliferating cell nuclear antigen index was higher in Group A compared with Group B (46.8+/-5.2 % vs. 31.1+/-3.7 %, p<0.05).
CONCLUSION
Local delivery of endothelin receptor blocker is effective in the prevention of stent restenosis in a porcine model, which may be related with the partial inhibition of cell proliferation of neointimal cells.

Keyword

Stent Restenosis; Local Delivery; Endothelin Receptor Blocker

MeSH Terms

Catheters
Cell Proliferation
Constriction, Pathologic
Coronary Artery Disease
Coronary Vessels
Endothelins*
Follow-Up Studies
Immunohistochemistry
Proliferating Cell Nuclear Antigen
Receptors, Endothelin*
Stents*
Endothelins
Proliferating Cell Nuclear Antigen
Receptors, Endothelin