首页> 外文期刊>Artificial Organs >Local glycoprotein IIb/IIIa receptor inhibitor delivery from the pump surface attenuates platelet adhesion in continuous flow ventricular assist devices.
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Local glycoprotein IIb/IIIa receptor inhibitor delivery from the pump surface attenuates platelet adhesion in continuous flow ventricular assist devices.

机译:从泵表面输送的局部糖蛋白IIb / IIIa受体抑制剂减弱了连续流心室辅助设备中的血小板粘附。

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摘要

Shear-induced platelet activation (SIPA) has been identified to induce platelet adhesion and thrombus formation in continuous flow left ventricular assist devices (LVAD). Platelet glycoprotein (GP) IIb/IIIa receptor inhibitors are effective to prevent SIPA. However, systemic GP IIb/IIIa receptor inhibitor application is associated with severe bleeding complications. The aim of the study was to evaluate (i) the feasibility of absorption and elution of the GP IIb/IIIa receptor blocker TAK-029 from the Ti6Al4V surface of the pump; and (ii) the effect of local GP IIb/IIIa receptor blocker delivery regarding platelet adhesion on the surface of a continuous flow VAD model. Saturating concentrations of TAK-029 were adsorbed on the surface of a centrifugal pump. Whole human blood was perfused in circulatory mock loops using untreated (control), albumin-coated, or TAK-029-coated pumps. Peripheral resistance of the circulatory systems were adjusted accordingly to generate 5 L flow per min with impeller rotational speeds of 3500 (high-shear group) and 1500 rpm (low-shear group), respectively. Platelet adhesions on the respective impellers were quantified by ELISA and scanning electron microscopy (SEM). TAK-029 elution and half-life time were determined by ELISA. Compared with control, albumin-coated pumps showed 64 and 20% less platelet adhesions in the high- and low-shear group, respectively. TAK-029 coated pumps reduced platelet adhesion by additional 33 and 65%, respectively, compared with the albumin group. Elution of TAK 029 was initially very rapid and continued slowly. The results show that it is possible to adsorb and elute a small molecular weight GP IIb/IIIa receptor blocker from the pump surface. This drug elution reduced platelet adhesion on the pump significantly. Further studies are necessary to find a suitable drug bonding that will prolong the antiplatelet effect and preclude any bleeding complication caused by this procedure.
机译:剪切诱导的血小板活化(SIPA)已被识别为在连续流动的左心室辅助装置(LVAD)中诱导血小板粘附和血栓形成。血小板糖蛋白(GP)IIb / IIIa受体抑制剂可有效预防SIPA。但是,全身性GP IIb / IIIa受体抑制剂的应用与严重的出血并发症相关。该研究的目的是评估(i)从泵的Ti6Al4V表面吸收和洗脱GP IIb / IIIa受体阻滞剂TAK-029的可行性; (ii)局部GP IIb / IIIa受体阻滞剂递送对连续流VAD模型表面血小板粘附的影响。 TAK-029的饱和浓度吸附在离心泵的表面。使用未经处理的(对照),白蛋白涂层或TAK-029涂层的泵在循环模拟循环中灌注全血。相应地调整循环系统的外围阻力,以每分钟产生5 L流量,叶轮转速分别为3500(高剪切力组)和1500 rpm(低剪切力组)。通过ELISA和扫描电子显微镜(SEM)定量在各个叶轮上的血小板粘附。通过ELISA确定TAK-029的洗脱和半衰期。与对照组相比,高剪切组和低剪切组的白蛋白包被的泵分别显示出少64%和20%的血小板粘附。与白蛋白组相比,TAK-029涂层泵分别减少了33%和65%的血小板粘附。 TAK 029的洗脱最初非常迅速,然后持续缓慢。结果表明,可以从泵表面吸附和洗脱小分子量GP IIb / IIIa受体阻滞剂。这种药物洗脱显着降低了泵上的血小板粘附。有必要进行进一步的研究以找到合适的药物结合,该药物结合可以延长抗血小板作用并避免由该程序引起的任何出血并发症。

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