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Effect of probucol on neointimal thickening in a stent porcine restenosis model.

Abstract
Restenosis after stent deployment remains a major clinical problem. Antioxidants have been proposed as a promising strategy against restenosis. We tested the antioxidant probucol for its efficacy against neointimal hyperplasia in porcine coronary arteries after stent implantation. Probucol was then tested in vivo in 8 coronary arteries of 4 pigs (1000 mg/day orally beginning 7 days before stenting) and was compared to placebo (10 coronary arteries, 5 pigs) 28 days after stenting. Quantitative intravascular ultrasound (IVUS) revealed 38.8 +/- 4.0 versus 40.1 +/- 3.0% area stenosis in the probucol versus control group. Histopathologic assessment showed that probucol had no beneficial effect on inhibiting the neointimal proliferative response in stent lesions compared to placebo (2.35 +/- 0.26 versus 2.88 +/- 0.25 mm(2)), despite similar injury scores (1.20 +/- 0.12 versus 1.28 +/- 0.14). An edge segment (axially 2-mm proximal to the stent margins) was assessed by IVUS. Remodeling index, which is a good marker of constrictive remodeling, was defined by the ratio of the vessel area in the lesion site (stent edge) to the vessel area in the proximal reference site (6-mm proximal to the stent margins). The remodeling index was significantly larger in the probucol group that in the placebo group (1.18 +/- 0.10 versus 0.90 +/- 0.06, P = 0.0012). In conclusion, probucol reduced constrictive remodeling at the edge of the implant but did not inhibit the tissue response within the stent.
AuthorsTakayuki Yokoyama, Katsumi Miyauchi, Takeshi Kurata, Hitoshi Sato, Hiroyuki Daida
JournalJapanese heart journal (Jpn Heart J) Vol. 45 Issue 2 Pg. 305-13 (Mar 2004) ISSN: 0021-4868 [Print] Japan
PMID15090707 (Publication Type: Journal Article)
Chemical References
  • Antioxidants
  • Probucol
Topics
  • Animals
  • Antioxidants (pharmacology)
  • Coronary Restenosis (pathology)
  • Coronary Vessels (pathology)
  • Disease Models, Animal
  • Probucol (pharmacology)
  • Random Allocation
  • Stents
  • Swine
  • Tunica Intima (drug effects)

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