洗脱血小板糖蛋白IIb/IIIa受体抗体的聚合物涂层支架的抗血栓形成潜力

Antithrombotic potential of polymer-coated stents eluting platelet glycoprotein IIb/IIIa receptor antibody.

作者信息

Aggarwal R K, Ireland D C, Azrin M A, Ezekowitz M D, de Bono D P, Gershlick A H

机构信息

Division of Cardiology, Faculty of Medicine, University of Leicester, UK.

出版信息

Circulation. 1996 Dec 15;94(12):3311-7. doi: 10.1161/01.cir.94.12.3311.

DOI:10.1161/01.cir.94.12.3311

PMID:8989145

Abstract

BACKGROUND

Monoclonal anti-rabbit platelet glycoprotein (GP) IIb/IIIa antibody (AZ1) was adsorbed onto cellulose polymer-coated intracoronary stents to enhance their thromboresistance. We evaluated the antithrombotic efficacy of AZ1 antibody-eluting stents.

METHODS AND RESULTS

Twenty-three polymer-coated stents with AZ1 antibody bound by passive adsorption (AZ1-eluting) were compared with 23 control polymer-coated stents adsorbed with either no antibody (base-polymer, n = 12) or isotype-matched irrelevant antibody (anti-CMV-eluting, n = 11) by implantation into balloon-damaged, flow-reduced iliac arteries of New Zealand White rabbits. In 13 animals (acute group), flow measurements were made with transit-time flow probes and platelet adhesion was ascertained by use of 111In-labeled autologous platelets. In the other 10 animals (chronic group), stent occlusion was assessed macroscopically after they were killed 28 days after stenting. Arteries with AZ1-eluting stents had significantly less platelet deposition (15.8 +/- 4.5 x 10(7)) than either base-polymer (32.1 +/- 4.3 x 10(7)) or anti-CMV-eluting (35.2 +/- 8.8 x 10(7)) controls (ANOVA, P < .0001). Compared with base-polymer or anti-CMV-eluting controls, arteries with AZ1-eluting stents showed a marked reduction in cyclic blood flow variation (P < .0001) and a significantly greater mean blood flow 2 hours after stent deployment (P < .0001). There was a significant improvement in the patency rate of AZ1-eluting stents compared with controls at both 2 hours (92% versus 46%, P = .034) and 28 days (100% versus 40%, P = .015).

CONCLUSIONS

Platelet GP IIb/IIIa antibody eluting from polymer-coated stents reduces platelet deposition, improves blood flow, virtually abolishes cyclic flow variation, and improves patency rates after stent implantation in a rabbit iliac artery model. Its potential for reducing stent-related thrombosis in humans warrants further evaluation.

摘要

背景

将单克隆抗兔血小板糖蛋白（GP）IIb/IIIa抗体（AZ1）吸附到纤维素聚合物涂层的冠状动脉支架上，以增强其抗血栓形成能力。我们评估了AZ1抗体洗脱支架的抗血栓疗效。

方法与结果

通过将23个通过被动吸附结合AZ1抗体的聚合物涂层支架（AZ1洗脱支架）与23个对照聚合物涂层支架进行比较，后者分别未吸附抗体（基础聚合物支架，n = 12）或吸附同型匹配的无关抗体（抗CMV洗脱支架，n = 11），将这些支架植入新西兰白兔球囊损伤、血流减少的髂动脉中。在13只动物（急性组）中，使用渡越时间血流探头进行血流测量，并通过使用111In标记的自体血小板确定血小板粘附情况。在另外10只动物（慢性组）中，在支架植入后28天处死动物，宏观评估支架闭塞情况。与基础聚合物支架（32.1±4.3×10⁷）或抗CMV洗脱支架（35.2±8.8×10⁷）相比，植入AZ1洗脱支架的动脉中血小板沉积显著减少（15.8±4.5×10⁷）（方差分析，P <.0001）。与基础聚合物支架或抗CMV洗脱支架相比，植入AZ1洗脱支架的动脉中循环血流变化显著降低（P <.0001），并且在支架植入后2小时平均血流显著增加（P <.0001）。与对照组相比，AZ1洗脱支架在2小时（92%对46%，P =.034）和28天（100%对40%，P =.015）时的通畅率均有显著改善。