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

项目摘要/摘要 该项目的目标是开发一种作为全心脏的植入式血泵系统 替补。左心辅助装置(LVAD)在END目的地治疗中的应用 阶段性心力衰竭正在扩大。然而，右心衰竭发生在10%-40%的LVAD中 病人。我们正在开发一种系统，该系统使用独立的离心式左泵和右泵 通用控制器。右心泵是基于为以下目的开发的右心替代泵 不及格的方坦病人。具有独特的双进气口，可连接上下位 腔静脉，允许将泵放置在右心房的位置。左边的泵是一个 设计类似的单进气泵。与目前可用的双心室辅助系统相比 和完全人工心脏相比，我们的做法将：1)让解剖上的配合通畅更小 患者，2)实现至少10年的可靠操作，3)自动调整左右 泵输出量以适应患者不同的生理需求4)左右平衡 在大范围的全身和肺循环中安全控制左房压力的泵输出 血管阻力和中心静脉压，5)提供搏动性血流，6)减少 血栓栓塞症和泵血栓的发生率，7)保留高分子量血管性血友病 威勒布兰德因子，以减少出血的发生率，并提供了一条发展道路，以 完全可植入的无线系统。具体目标1-建立双心室替换术 替换衰竭心脏的装置，右心放置在双腔位置，左心放置在左心 泵与左心房残端吻合。两台泵中压力传感器的集成 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 能够对两台泵进行生理控制的系统。控制器将增加右泵 输出量对静脉回流增加的反应，这模仿了正常的Frank-Starling心脏 输出响应，并控制左心泵输出，将左房压力维持在生理范围内 射程。该控制器还将调节泵的速度，以产生脉动流量。具体目标3- 在慢性动物研究中测试和优化TAH，以：A)演示自动Starling样 泵的心输出量控制和自动平衡控制范围广泛 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兼容性 评估血栓形成、血栓栓塞症、von Willebrand因子降解以及 肠道血管发育不良。我们将研究脉动模和非脉动模。

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.