普罗布考对支架再狭窄猪新内膜厚度的作用

Yokoyama T etal. Jpn Heart J. 2004;45(2):305-13

支架植入后的再狭窄仍然是临床的主要问题。已提出抗氧化作为有希望的抗再狭窄对策。我们试验了抗氧化剂普罗布考对猪冠状动脉支架植入后新内膜增生的作用。普罗布考组为4头猪8支冠状动脉，支架植入前7天开始口服1000mg/天；安慰剂组为5头猪10支冠状动脉，支架植入后试验28天。定量血管内超声（IVUS）显示，普罗布考组对对照组的面积狭窄为38.8+/-4.0%对40.1+/-3.0%。组织病理学鉴定表明，普罗布考对支架损伤没有抑制心内膜增生的作用，与安慰剂分别为2.35 +/- 0.26 对 2.88 +/- 0.25 mm2，其损伤斑块类似，为1.20 +/- 0.12 对 1.28 +/- 0.14。用IVUS评价边缘段（接近于支架边缘的向轴方向2mm）。重塑指数是收缩性重塑的良好指标，是损伤位置（支架边缘）的血管面积对邻近参考位置（接近于支架边缘6mm）的血管面积的比值。普罗布考组的重塑指数较安慰剂组明显地大(1.18 +/- 0.10 对 0.90 +/- 0.06, P = 0.0012)。结论，普罗布考在植入边缘降低收缩性重塑，但不抑制支架内的组织反应。

Jpn Heart J. 2004 Mar;45(2):305-13.
 
Effect of probucol on neointimal thickening in a stent porcine restenosis model.

Yokoyama T, Miyauchi K, Kurata T, Sato H, Daida H.

Department of Cardiovascular Medicine, Juntendo University, Tokyo, Japan.

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.