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

项目总结/摘要 本项目的目标是开发一种植入式血泵系统作为全心脏 更换.使用左心室辅助装置（LVAD）进行终点治疗 阶段性心力衰竭正在扩大然而，10-40%的LVAD发生右心室衰竭 患者我们正在开发一种使用单独的离心式左泵和右泵的系统， 通用控制器右泵是基于右心脏置换泵开发的， 失败的丰唐病人它具有独特的双入口端口，可连接到上级和低级 腔静脉，允许泵放置在右心房的位置。左泵是一个 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）允许在较小的解剖结构中畅通无阻 患者，2）实现至少10年的可靠运行，3）自动调节左右 泵输出以响应患者的不同生理需求4）左右平衡 泵输出可在全身和肺动脉压力范围内安全控制左心房压力 血管阻力和中心静脉压，5）提供脉动流，6）减少 血栓栓塞和泵血栓形成发生率，7）保留高分子量血管内皮细胞 Willebrand因子降低出血的发生率，和8）提供了一个发展途径， 完全可植入的无线系统具体目标1-构建双心室置换术 装置，以取代衰竭的心脏，与右心放置在双腔的立场和左 泵关闭至左心房残余物。在两台泵中集成压力传感器 将测量入口压力（相当于右心房和左心房压力）， 用作自动控制系统的输入。具体目标2-开发自动控制 能够对两个泵进行生理控制的系统。控制器将增加右泵 输出响应于静脉回流增加，其模拟正常的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压力范围内。 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）证明自动Starling样 心输出量控制和泵的自动平衡控制， 包括运动在内的生理条件，和B）通过以下方式检查器械的生物相容性： 评估血栓形成、血栓栓塞、血管性血友病因子降解，以及 肠血管发育不良我们将研究脉动和非脉动模式。

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.