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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。

结论

从聚合物涂层支架洗脱的血小板GP IIb/IIIa抗体可减少血小板沉积,改善血流,几乎消除循环血流变化,并提高兔髂动脉模型中支架植入后的通畅率。其在人类中降低支架相关血栓形成的潜力值得进一步评估。

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