A Structured Approach to the Design of Minimally Traumatic Blood Pumps

微创血泵设计的结构化方法

• 批准号: 9924643
• 负责人: KEEFE B MANNING
• 金额: $ 61.74万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-05-25 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9924643
• 关键词: Address; Adhesions; Adverse effects; Adverse event; Animal Testing; Animals; Anticoagulation; Artificial Heart; Blood; Blood Platelets; Cardiovascular system; Clinical; Clinical Data; Clinical Trials; Coagulation Process; Code; Communication; Complex; Computer Models; Computer Simulation; Computing Methodologies; Couples; Critical Pathways; Destinations; Development; Devices; Geometry; Goals; Heart; Heart Valves; Heart failure; Hemolysis; Hemorrhage; Immune system; Implant; In Vitro; Individual; Ischemic Stroke; Liquid substance; Location; Measures; Methods; Modeling; Morbidity - disease rate; Operative Surgical Procedures; Patients; Performance; Phase; Physics; Platelet Activation; Predisposition; Process; Pulsatile Flow; Pump; Reporting; Research; Resolution; Safety; Severities; Site; Source Code; Speed; Stroke; Structure; Study models; Surgical complication; System; Testing; Therapeutic Embolization; Thromboembolism; Thrombosis; Thrombus; Time; Transplantation; United States Food and Drug Administration; Whole Blood; base; blood damage; blood pump; computational platform; design; improved; in vivo; left ventricular assist device; models and simulation; open source; pre-clinical; preclinical development; prototype; shear stress; simulation; stroke incidence; temporal measurement; tool; ventricular assist device

Project Summary / Abstract The objective of this research is to develop improved analytical and experimental methods used in a structured approach for the design of blood pumps with reduced potential for adverse events. We propose to continue our efforts focusing on the development of a computational platform using an open source code that integrates and couples shear-induced blood damage, thrombosis susceptibility potential, platelet activation, and thrombosis models simultaneously during the design process. Currently, only hemolysis models are used in the design phase and platelet activation used in rare cases, but neither has been integrated into a single computational model simultaneously. Our use of large eddy simulation computational fluid dynamics (CFD) provides a flow field capturing much of the turbulent flow field. We will apply this structured approach on a prototype bladed rotary ventricular assist device (VAD) that we are developing. To accomplish these goals, we will focus on the following specific aims: 1. Integrate a newly developed shear-induced blood damage model based upon dissipation (7), a thrombosis susceptibility potential (TSP) (8-10), and a platelet activation model (11) into a single computational platform to design a rotary blood pump incorporating the interaction of the VAD and native heart pulsatility. This research is intended to culminate in inclusion of a continuum-based macroscopic thrombosis model to refine the pump design. 2. Develop a continuum-based macroscopic thrombosis model for both laminar and turbulent flow and shear induced platelet activation that will be used to refine the pump design. The thrombosis model will be validated through in vitro platelet adhesion studies using a rotating disk system (RDS), an in vitro backward facing step (BFS) model using whole blood, and clinical LVAD patients. 3. Perform in vivo animal studies of a prototype rotary VAD system in non-anticoagulated animals to a) assess location, severity, and time course of thrombosis and embolization, b) study the effect of pump speed and pulsatile flow, and c) measure platelet activation, global coagulation, and hemolysis. This research will yield improved design and analysis tools in a structured approach that will be applicable to a broad range of blood pumps and blood contacting cardiovascular devices.

项目总结/摘要 本研究的目的是开发改进的分析和实验方法，用于结构化 降低不良事件可能性的血泵设计方法。我们建议继续我们的 致力于开发一个使用开源代码的计算平台， 和夫妇剪切诱导的血液损伤，血栓形成易感性的潜力，血小板活化， 血栓模型同时在设计过程中。目前，只有溶血模型用于 设计阶段和血小板活化在罕见的情况下使用，但两者都没有被整合到一个单一的 计算机模型同时我们使用大涡模拟计算流体动力学（CFD） 提供捕获大部分湍流场的流场。我们将把这种结构化方法应用于 我们正在开发的原型叶片旋转心室辅助装置（VAD）。为了实现这些目标，我们 将侧重于以下具体目标： 1.整合新开发的基于耗散的剪切诱导血液损伤模型（7），血栓形成 易感性电位（TSP）（8-10）和血小板活化模型（11）合并为单个计算模型 该平台用于设计结合VAD和天然心脏脉动的相互作用的旋转血泵。 本研究旨在最终纳入基于连续体的宏观血栓形成模型， 完善泵的设计。 2.开发一个基于连续介质的宏观血栓模型，用于层流、湍流和剪切 诱导的血小板活化，将用于完善泵的设计。血栓形成模型将是 通过使用旋转盘系统（RDS）的体外血小板粘附研究进行验证， 使用全血和临床LVAD患者的面向台阶（BFS）模型。 3.在非抗凝动物中进行原型旋转VAD系统的体内动物研究，以a） 评估血栓形成和栓塞的位置、严重程度和时间过程，B）研究泵的作用 速度和脉动流，以及c）测量血小板活化、整体凝固和溶血。 这项研究将产生改进的设计和分析工具的结构化方法，将适用于 广泛的血泵和血液接触心血管设备。