Effect of probucol on neointimal thickening in a stent porcine restenosis model.
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.
Yokoyama
Takayuki
T
Department of Cardiovascular Medicine, Juntendo University, Tokyo, Japan.
Miyauchi
Katsumi
K
Kurata
Takeshi
T
Sato
Hitoshi
H
Daida
Hiroyuki
H
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D023903:Coronary Restenosis / Q000473:pathology; D003331:Coronary Vessels / Q000473:pathology*; D004195:Disease Models, Animal; D011341:Probucol / Q000494:pharmacology*; D011897:Random Allocation; D015607:Stents; D013552:Swine; D017539:Tunica Intima / Q000187:drug effects*
D000975:Antioxidants; D011341:Probucol