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

 描述（由申请人提供）：本项目的目标是开发一种小型化的小儿版TORVADTM，这是一种独特的心室辅助系统，可在环形腔内使用受控活塞运动输送低剪切、同步、脉动流。低剪切是通过相对较低的活塞速度与局部流体动力轴承结合实现的，该局部流体动力轴承将大体积活塞-环面间隙保持在固定距离。TORVAD通过Frank-Starling机制与心脏一起维持主动脉瓣血流并维持心输出量的自动调节。TORVAD的设计还允许在没有附加传感器的情况下固有地确定泵压差，这可用于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，与连续流装置相比，低剪切设计保留了高分子量血管性血友病因子，并导致溶血显著减少。此外，使用急性和慢性动物模型证明了血液动力学相容性。TORVAD的血液学结果是任何其他心室辅助设备无法比拟的。这些初步结果表明，TORVAD有可能减少与使用其他心室辅助器械相关的出血、血栓形成和卒中。该项目的目标是开发 TORVAD的儿科版本，用于体表面积（BSA）在0.6和1.5 m2之间的患者。儿童TORVAD的可行性已通过成人版本的开发和测试得到证明，其中使用血液动力学、传热、电机设计、流体动力学和静磁学的计算模型来设计、制造和验证组装泵的性能。在这项工作中，我们将（1）使用已建立的计算设计方法来验证BSA在0.6和1.5 m2之间的儿科患者的器械;（2）制造五个器械并进行设计验证;（3）进行体外实验以评估溶血、高分子量血管性血友病因子保存和血小板活化;和（4）进行三次急性动物实验以评估可植入性、血液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.