Application of Ex Vivo Flow Chamber System for Assessment of Stent Thrombosis

M. Sakakibara, S. Goto, K. Eto, N. Tamura, T. Isshiki, S. Handa
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引用次数: 21

Abstract

Objective—Factors influencing platelet accumulation around stents were to be investigated by an ex vivo flow chamber system. Methods and Results—Platelet accumulations on collagen surfaces under flow conditions were augmented in the presence of stents, especially at sites downstream from coil stents. Densitometric analysis revealed that 4.9±0.8 times more platelets accumulated downstream from coil stents than were formed downstream from tube stents (P <0.01), suggesting that stent morphology is an important determinant factor of its thrombogenicity. Platelet accumulations around stents were significantly inhibited by a combination of ticlopidine and aspirin, whereas aspirin alone produced only modest inhibition. Anti–glycoprotein IIb/IIIa (abciximab) inhibited platelet accumulation around stents in a dose-dependent manner, whereas the antibody blocking von Willebrand factor binding to glycoprotein Ib&agr;, which had been shown to inhibit platelet thrombus formation under high shear rates, did not inhibit the accumulation downstream from the coil stents. Our results suggest that the important characteristics of in vivo stent thrombosis, ie, augmented platelet accumulation with coil stents and the strong antithrombotic effect of the combination antiplatelet agents and an anti–glycoprotein IIb/IIIa, can be reproduced in ex vivo perfusion model. Conclusions—We conclude that an ex vivo perfusion system is useful in the assessment of the thrombogenicity of various stents and in the screening of effective antiplatelet agents.
体外血流室系统在评估支架血栓形成中的应用
目的:通过体外血流室系统研究影响支架周围血小板聚集的因素。方法与结果:在血流条件下,支架存在时,胶原表面的血小板聚集增加,尤其是在线圈支架的下游部位。密度分析显示,线圈支架下游积聚的血小板是管状支架下游形成血小板的4.9±0.8倍(P <0.01),表明支架形态是其血栓形成的重要决定因素。噻氯匹定和阿司匹林联合使用可以显著抑制支架周围的血小板聚集,而阿司匹林单独使用只能产生适度的抑制作用。抗糖蛋白IIb/IIIa(阿昔单抗)以剂量依赖的方式抑制支架周围的血小板积聚,而阻断与糖蛋白Ib&agr结合的血管性血友病因子抗体,已被证明可以抑制高剪切速率下血小板血栓的形成,但不抑制线圈支架下游的血小板积聚。我们的研究结果表明,体内支架血栓形成的重要特征,即线圈支架增加血小板积聚,以及抗血小板药物和抗糖蛋白IIb/IIIa联合使用的强抗血栓作用,可以在体外灌注模型中重现。结论:体外灌注系统在评估各种支架的血栓形成性和筛选有效的抗血小板药物方面是有用的。
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