Ishiwata S, Verheye S, Robinson K A, Salame M Y, de Leon H, King S B, Chronos N A
Andreas Gruentzig Cardiovascular Center, Department of Medicine (cardiology), Emory University School of Medicine, Atlanta, Georgia, USA.
J Am Coll Cardiol. 2000 Apr;35(5):1331-7. doi: 10.1016/s0735-1097(00)00528-3.
We evaluated the effect of orally administered tranilast, N-(3,4-dimethoxycinnamoyl) anthranilic acid, on histologic and histomorphometric changes after angioplasty or stent implantation in pig coronary arteries.
Tranilast, which has antikeloid and antiallergic properties and therefore may modulate the fibrotic and inflammatory tissue responses to angioplasty and stenting, has been shown to inhibit angiographic restenosis in small clinical trials. However, its effect on histomorphometric changes in coronary arteries after angioplasty and stenting is unknown.
Following initial pharmacokinetic studies in two pigs to determine desirable plasma levels of orally administered tranilast, 36 crossbred juvenile pigs were randomized to placebo or tranilast before undergoing balloon angioplasty in both the left anterior descending and left circumflex plus stent implantation in the right coronary artery. Oral tranilast was administered at 3 g/day starting 3 days before coronary injury and continued for 28 days until euthanasia. Injured vessels were harvested and sections analyzed by computer-assisted microscopic planimetry.
In balloon-injured vessels, tranilast was associated with a 37% reduction in neointimal area normalized to fracture length (0.47 +/- 0.01 vs. 0.74 +/- 0.03 mm; p < 0.001) and a 23% reduction in adventitial area normalized to vessel size (0.43 +/- 0.02 vs. 0.56 +/- 0.03; p = 0.003). In stented arteries, neointimal area normalized to injury score was 32% lower in the tranilast-treated group compared to control (1.94 +/- 0.17 vs. 2.86 +/- 0.29; p = 0.01).
In pig coronary arteries, tranilast was associated with a reduction in neointima formation and adventitial reaction after balloon injury. In stented vessels, tranilast was associated with a reduction in neointima formation normalized to injury score.
我们评估了口服曲尼司特（N-(3,4-二甲氧基肉桂酰)邻氨基苯甲酸）对猪冠状动脉血管成形术或支架植入术后组织学和组织形态计量学变化的影响。
曲尼司特具有抗瘢痕疙瘩和抗过敏特性，因此可能调节对血管成形术和支架植入术的纤维化和炎症组织反应，在小型临床试验中已显示可抑制血管造影再狭窄。然而，其对血管成形术和支架植入术后冠状动脉组织形态计量学变化的影响尚不清楚。
在对两头猪进行初步药代动力学研究以确定口服曲尼司特的理想血浆水平后，36头杂交幼猪在左前降支进行球囊血管成形术以及在右冠状动脉进行支架植入术前被随机分为安慰剂组或曲尼司特组。口服曲尼司特从冠状动脉损伤前3天开始，每天3克，持续28天直至安乐死。收集损伤血管并通过计算机辅助显微镜平面测量法分析切片。
在球囊损伤血管中，曲尼司特使归一化至断裂长度的新生内膜面积减少37%（0.47±0.01对0.74±0.03平方毫米；p<0.001），使归一化至血管大小的外膜面积减少23%（0.43±0.02对0.56±0.03；p = 0.003）。在植入支架的动脉中，与对照组相比，曲尼司特治疗组归一化至损伤评分的新生内膜面积低32%（1.94±0.17对2.86±0.29；p = 0.01）。
在猪冠状动脉中，曲尼司特与球囊损伤后新生内膜形成和外膜反应减少有关。在植入支架的血管中，曲尼司特与归一化至损伤评分的新生内膜形成减少有关。
