Development of a Universal Bi-ventricular Replacement System for the Failing Heart

开发用于衰竭心脏的通用双心室置换系统

• 批准号: 10210500
• 负责人: Joshua P Cysyk
• 金额: $ 78.42万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10210500
• 关键词: Acute; Anatomy; Angiodysplasia; Animal Testing; Animals; Blood Tests; Cannulations; Cardiac Output; Cattle; Central venous pressure; Chronic; Complex; Destinations; Development; Device Designs; Devices; Electronics; Equilibrium; Exercise; Failure; Funding; Future; Generations; Heart; Heart Atrium; Heart Transplantation; Heart failure; Hemolysis; Hemorrhage; Hemostatic function; Implant; Incidence; Inferior; Intestines; Journals; Left; Left atrial structure; Liquid substance; Measures; Methods; Modeling; Molecular Weight; Motor; Operative Surgical Procedures; Output; Patients; Physiological; Positioning Attribute; Pulmonary Vascular Resistance; Pulsatile Flow; Pulse Pressure; Pump; Quality of life; Right atrial structure; Risk; Speed; Sturnus vulgaris; System; Testing; Thromboembolism; Thrombosis; Thrombus; Time; Tube; Universities; Vascular resistance; Venous; Ventricular; Wireless Technology; base; biomaterial compatibility; blood pump; cost; design; experience; flexibility; human disease; left ventricular assist device; mortality; operation; preservation; pressure; pressure sensor; response; total artificial heart; transmission process; treadmill; von Willebrand Factor

Project Summary/Abstract The objective of this project is to develop an implantable blood pump system as a total heart replacement. The use of left ventricular assist devices (LVADs) for destination therapy for end stage heart failure is expanding. However, right ventricular failure occurs in 10-40% of LVAD patients. We are developing a system using separate centrifugal left and right pumps with a common controller. The right pump is based on a right heart replacement pump developed for failing Fontan patients. It has unique double inlet ports to connect to the superior and inferior vena cavae, allowing the pump to be placed in the position of the right atrium. The left pump is a single inlet pump of similar design. Compared to currently available biventricular assist systems and total artificial hearts, our approach will: 1) allow unobstructed fit in the anatomy of smaller patients, 2) achieve reliable operation for at least 10 years, 3) automatically adjust left and right pump output to respond to the varied physiologic needs of the patient 4) balance left and right pump outputs to safely control left atrial pressure over a wide range of systemic and pulmonary vascular resistances and central venous pressures, 5) provide pulsatile flow, 6) reduce the incidence of thromboembolism and pump thrombosis, 7) preserve high molecular weight von Willebrand factor to reduce the incidence of bleeding, and 8) provide a development path to a completely implantable, wireless system. Specific Aim 1- Build a biventricular replacement device to replace the failing heart, with the right heart placed in the bicaval position and a left pump anastomosed to the left atrium remnant. Integration of pressure sensors in both pumps will measure inlet pressures (equivalent to right atrial and left atrial pressures), which will be used as inputs to the automatic control system. Specific Aim 2- Develop an automatic control system capable of physiologic control of both pumps. The controller will increase right pump output in response to increased venous return, which mimics the normal Frank-Starling cardiac output response, and control left pump output to maintain left atrial pressure within a physiologic range. The controller will also modulate pump speeds to produce pulsatile flow. Specific Aim 3- Test and optimize the TAH in chronic animal studies to: A) Demonstrate automatic Starling-like cardiac output control and automatic balance control of the pumps over a wide range of physiologic conditions including exercise, and B) examine the biocompatibility of the device by assessing thrombus formation, thromboembolism, von Willebrand factor degradation, and intestinal angiodysplasia. We will study both pulsatile and non-pulsatile modes.

项目概要/摘要 该项目的目标是开发一种植入式血泵系统作为全心脏 替代品。使用左心室辅助装置 (LVAD) 进行终点治疗 心力衰竭阶段正在扩大。然而，10-40% 的 LVAD 患者会出现右心室衰竭 患者。我们正在开发一种使用独立的左、右离心泵的系统 通用控制器。正确的泵基于为右心置换而开发的泵 失败的 Fontan 患者。具有独特的双进水口，可连接上、下 腔静脉，允许将泵放置在右心房的位置。左边的泵是 类似设计的单入口泵。与目前可用的双心室辅助系统相比 和全人工心脏，我们的方法将：1）允许无障碍地适应较小的解剖结构 患者，2）实现至少10年的可靠运行，3）自动左右调节 泵输出量可响应患者不同的生理需求 4) 左右平衡 泵输出可安全控制广泛的全身和肺左心房压力 血管阻力和中心静脉压，5) 提供脉动血流，6) 减少 血栓栓塞和泵血栓的发生率，7) 保留高分子量冯 血友病因子可减少出血的发生率，8) 提供一条发展道路 完全植入式无线系统。具体目标 1 - 构建双心室替代物 用于替代衰竭心脏的装置，右心置于双腔位置，左心置于双腔位置 泵与左心房残余物吻合。两个泵中均集成了压力传感器 将测量入口压力（相当于右心房和左心房压力），这将是 用作自动控制系统的输入。具体目标 2 - 开发自动控制 系统能够对两个泵进行生理控制。控制器将增加右泵 输出响应增加的静脉回流，模仿正常的 Frank-Starling 心脏 输出响应，并控制左泵输出以将左心房压力维持在生理范围内 范围。控制器还将调节泵速以产生脉动流。具体目标 3- 在慢性动物研究中测试和优化 TAH，以：A) 展示自动的 Starling 样 各种泵的心输出量控制和自动平衡控制 包括运动在内的生理条件，以及 B) 通过以下方式检查设备的生物相容性： 评估血栓形成、血栓栓塞、血管性血友病因子降解，以及 肠道血管发育不良。我们将研究脉动和非脉动模式。