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首页> 外文期刊>Artificial Organs >The impact of shear stress on device‐induced platelet hemostatic dysfunction relevant to thrombosis and bleeding in mechanically assisted circulation
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The impact of shear stress on device‐induced platelet hemostatic dysfunction relevant to thrombosis and bleeding in mechanically assisted circulation

机译：剪切应力对装置诱导的血小板止血功能障碍与机械辅助循环中的血栓形成和出血相关的影响

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Abstract The aim of this study was to examine the impact of the nonphysiological shear stress (NPSS) on platelet hemostatic function relevant to thrombosis and bleeding in mechanically assisted circulation. Fresh human blood was circulated for four hours in in vitro circulatory flow loops with a CentriMag blood pump operated under a flow rate of 4.5?L/min against three pressure heads (70 mm?Hg, 150 mm?Hg, and 350 mm?Hg) at 2100, 2800, and 4000 rpm, respectively. Hourly blood samples from the CentriMag pump‐assisted circulation loops were collected and analyzed for glycoprotein (GP) IIb/IIIa activation and receptor shedding of GPVI and GPIbα on the platelet surface with flow cytometry. Adhesion of platelets to fibrinogen, collagen, and von Willebrand factor (VWF) of the collected blood samples was quantified with fluorescent microscopy. In parallel, mechanical shear stress fields within the CentriMag pump operated under the three conditions were assessed by computational fluid dynamics (CFD) analysis. The experimental results showed that levels of platelet GPIIb/IIIa activation and platelet receptor shedding (GPVI and GPIbα) in the blood increased with increasing the circulation time. The levels of platelet activation and loss of platelet receptors GPVI and GPIbα were consistently higher with higher pressure heads at each increasing hour in the CentriMag pump‐assisted circulation. The platelet adhesion on fibrinogen increased with increasing the circulation time for all three CentriMag operating conditions and was correlated well with the level of platelet activation. In contrast, the platelet adhesion on collagen and VWF decreased with increasing the circulation time under all the three conditions and was correlated well with the loss of the receptors GPVI and GPIbα on the platelet surface, respectively. The CFD results showed that levels of shear stresses inside the CentriMag pump under all three operating conditions exceeded the maximum level of shear stress in the normal physiological circulation and were strongly dependent on the pump operating condition. The level of platelet activation and loss of key platelet adhesion receptors (GPVI and GPIbα) were correlated with the level of NPSS generated by the CentriMag pump, respectively. In summary, the level of NPSS associated with pump operating condition is a critical determinant of platelet dysfunction in mechanically assisted circulation.
机译：摘要本研究的目的是检查非物理剪切应激（NPS）对与机械辅助循环中血栓形成和出血相关的血小板止血功能的影响。在体外循环流动环中循环新鲜的人血液4小时，用Centrimag血液泵在4.5μl/ min的流速下操作，针对三个压力头（70mmΔHg，150mm？hg和350mm？hg ）分别在2100,2800和4000 rpm。收集来自Centrimag泵辅助循环环的每小时血液样本，并分析糖蛋白（GP）IIB / IIIA活化和GPVI和GPIBα的受体脱落，流式细胞术在血小板表面上。用荧光显微镜量化收集的血液样品的血小板与纤维蛋白原，胶原和von willebrand系数（vwf）的粘附性。在三个条件下，通过计算流体动力学（CFD）分析来评估在三个条件下操作的Centrimag泵内的机械剪切应力场。实验结果表明，随着循环时间的增加，血小板GPIIB / IIIa活化和血小板受体脱落（GPVI和GPIBα）的水平增加。血小板活化和血小板受体损失的水平GPVI和GPIBα在Centrimag泵辅助循环中的每个增加的小时内始终较高。纤维蛋白原上的血小板粘附随着所有三个中心操作条件的循环时间增加，并且随着血小板活化水平良好相关。相比之下，随着在所有三种条件下的循环时间增加，胶原蛋白和VWF的血小板粘附性分别随着受体GPVI和GPIBα的损失分别在血小板表面上的损失而良好。 CFD结果表明，在所有三个操作条件下，Centrimag泵内的剪切应力水平超过正常生理循环中的最大剪切应力水平，并且强烈依赖于泵操作条件。血小板活化水平和关键血小板粘附受体（GPVI和GPIBα）的损失分别与由Centrimag泵产生的NPS水平相关。总之，与泵操作条件相关的NPS的水平是机械辅助循环中的血小板功能障碍的关键决定因素。

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