Miniaturization of the low-shear pulsatile TORVAD for pediatric heart failure

 描述(由申请人提供)：该项目的目标是开发一种小型化的儿科版本的TORVADTM，这是一种独特的心脏辅助系统，使用环形腔内受控的活塞运动，提供低剪切、同步、脉动的血流。低剪切是由相对较低的活塞速度与本地化的流体动力轴承相结合实现的，这些轴承在固定距离上保持大量活塞-环隙。TORVAD与心脏同步，以保护主动脉瓣血流，并通过Frank-Starling机制维持心输出量的自动调节。TORVAD的设计还允许固有地确定差压泵的压力，而不需要额外的传感器，可以用来管理患者的药物和流速。这些优势已在成人TORVAD的初步研究中得到证实。体外试验表明，与连续流动装置相比，低剪切设计保留了高分子量的von Willebrand因子，并显著减少了溶血。此外，血液动力学兼容性已在急性和慢性动物模型中得到证实。TORVAD的血液学结果是任何其他脑室辅助设备无法比拟的。这些初步发现表明，TORVAD有可能减少与使用其他脑室辅助装置相关的出血、血栓形成和中风。这个项目的目标是开发 体表面积(BSA)在0.6至1.5平方米之间的患者使用的TORVAD的儿科版本。通过成人版的开发和测试，证明了儿科TORVAD的可行性，其中血液动力学、传热学、马达设计、流体动力学和静磁场的计算模型被用于设计、制造和验证组装的泵的性能。在这项工作中，我们将(1)使用已建立的计算设计方法将BSA在0.6至1.5平方米之间的儿科患者设备微型化；(2)制造五台设备并进行设计验证；(3)进行体外实验以评估溶血、高分子量von Willebrand因子保存和血小板激活；以及(4)进行三项急性动物实验以评估植入性、血流动力学性能和同步性。

 DESCRIPTION (provided by applicant): The goal of this project is to develop a miniaturized, pediatric version of the TORVADTM, a unique ventricular assist system that delivers low-shear, synchronous, pulsatile flow, using controlled piston motion within a toroidal chamber. Low shear is achieved by the relatively low piston speed in conjunction with localized hydrodynamic bearings that maintain bulk piston-torus gap at a fixed distance. The TORVAD synchronizes with the heart to preserve aortic valve flow and maintains autoregulation of cardiac output by the Frank-Starling mechanism. The design of the TORVAD also allows for inherent determination of differential pump pressure, without additional sensors, which can be used to manage patient's medications and flow rates. These advantages have been confirmed in preliminary studies with an adult TORVAD. In vitro tests have demonstrated that the low-shear design preserves high-molecular-weight von Willebrand factor and results in significantly reduced hemolysis as compared to a continuous flow device. In addition, hemodynamic compatibility has been demonstrated using acute and chronic animal models. The TORVAD's hematological results are unmatched by any other ventricular assist device. These preliminary findings demonstrate that the TORVAD has the potential to reduce bleeding, thrombus formation, and strokes that are associated with the use of other ventricular assist devices. The goal of this project is to develop a pediatric version of the TORVAD to be used in patients with body surface area (BSA) between 0.6 and 1.5 m2. The feasibility of a pediatric TORVAD has been demonstrated through the development and testing of the adult version, where computational models for hemodynamics, heat transfer, motor design, fluid dynamics, and magnetostatics were used to design, fabricate, and verify performance with the assembled pump. For this work we will (1) Use the established computational design methodology to miniaturize the device for pediatric patients with a BSA between 0.6 and 1.5 m2; (2) Fabricate five devices and perform design verification; (3) Conduct in vitro experiments to assess hemolysis, high-molecular-weight von Willebrand factor preservation, and platelet activation; and (4) Perform three acute animal experiments to assess implantability, hemodynamic performance, and synchronization.