New Methodologies for the Design of Small Blood Pumps

描述（由申请人提供）：本研究的目的是继续开发血泵开发的综合方法，以降低患者中血栓栓塞和血流相关不良事件的发生率。我们以前曾采用类似的方法来减少脉动式左心室辅助装置（LVAD）中的血栓栓塞。在这个项目中，我们将这些方法应用到一个创新的旋转剪切流LVAD。具体目标是：1）将为脉动泵开发的计算流体动力学（CFD）模型扩展到独特的旋转血泵。验证和完善将基于实验流体动力学（EFD）测量的血液动力学性能，流体速度，壁面剪切力和雷诺应力，使用粒子图像测速仪（PIV）和激光多普勒测速仪（LDV），并在体外溶血测试。2)通过将我们用于脉动泵流的模型扩展到旋转血泵的流态，将TSP血栓模型、血小板活化模型和溶血模型纳入我们的计算流体动力学（CFD）代码。我们将利用剪切依赖性血小板粘附的体外试验（旋转圆盘）和体外溶血研究来校准/验证模型。3)在非抗凝动物中进行完整VAD系统的体内研究，以1）评估血栓形成和栓塞的位置、严重程度和时程，2）研究泵速和脉动流的影响，3）测量血小板活化、整体凝血、溶血和肾缺血的生物标志物。4)利用CFD和计算建模方法，开发并验证体外和体内试验方法的数据，优化剪切流锥盘设计，以最大限度地减少血栓形成。实验设计（DOE）析因设计技术将用于根据加权成本函数制定测试计划。这项研究将产生改进的方法，设计，分析和测试，将适用于广泛的旋转和脉动装置。

DESCRIPTION (provided by applicant): The objective of this research is to continue development of an integrated approach to blood pump development, in order to reduce the incidence of thromboembolic and flow-related adverse events in patients. We have previously applied a similar approach to reducing thromboembolism in a pulsatile left ventricular assist device (LVAD). In this project we will apply these methods to an innovative rotary shear flow LVAD. The specific aims are to: 1) Extend a computational fluid dynamics (CFD) model developed for pulsatile pumps to a unique rotary blood pumps. Validation and refinement will be based on experimental fluid dynamic (EFD) measurements of hemodynamic performance, fluid velocities, wall shear and Reynolds stresses, using particle image velocimetry (PIV) and laser Doppler velocimetry (LDV), and in-vitro hemolysis testing. 2) Incorporate a TSP thrombosis model, platelet activation model and hemolysis model into our computational fluid dynamics (CFD) code by extending models we have used for pulsatile pump flows, to the flow regimes of rotary blood pumps. We will utilize in vitro tests (rotary disc) of shear-dependent platelet adhesion, and in vitro hemolysis studies to calibrate/validate the model. 3) Perform in vivo studies of complete VAD systems in non-anticoagulated animals to 1) assess location, severity, and time course of thrombosis and embolization, 2) study the effect of pump speed and pulsatile flow, and 3) measure platelet activation, global coagulation, hemolysis, and biomarkers of renal ischemia. 4) Utilize the CFD and computational modeling methods, developed and validated with data from the in vitro and in vivo test methods, to optimize the shear flow cone disc design to minimize thrombosis. A Design of Experiment (DOE) factorial design technique will be used to develop a test plan based upon a weighted cost function. This research will yield improved methods for design, analysis, and testing that will be applicable to a broad range of rotary and pulsatile devices.