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.

项目摘要/摘要 该项目的目的是开发一个可植入的血液泵系统作为总心脏 替代品。使用左心室辅助设备（LVADS）进行目的地治疗 舞台心力衰竭正在扩大。但是，右心衰竭发生在10-40％的LVAD中 患者。我们正在使用单独的离心左和右泵开发一个系统 普通控制器。正确的泵基于为右心脏替换泵开发的 Fontan患者失败。它具有独特的双入口端口，可连接到上级和下等 腔腔，使泵放在右心房的位置。左泵是 类似设计的单个入口泵。与当前可用的双室辅助系统相比 和人造心脏，我们的方法将：1）允许在较小的解剖结构中毫无疑问 患者，2）至少实现可靠的操作10年，3）自动调整左右调整 泵输出以响应患者的各种生理需求4）左右平衡 泵输出以安全控制在多种全身和肺部左心压 血管抗性和中央静脉压力，5）提供脉动流动，6）降低 血栓栓塞和泵血栓形成的发生率，7）保留高分子量von 降低出血的发生率的威勒布氏因子，8）为A提供了开发路径 完全植入，无线系统。特定目标1-建立双脑室替代品 替换失败心脏的设备，右心放在双凸位置和左侧 泵吻合到左心房残留物。两个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。特定目标2-开发自动控制 能够对两个泵的生理控制的系统。控制器将增加正确的泵 响应增加的静脉回流的输出，这模仿了普通的坦率坦率心脏的心脏 输出响应和控制左泵输出以在生理中保持左心压 范围。控制器还将调节泵速度以产生脉动流动。特定目标3- 在慢性动物研究中测试并优化TAH至： 心脏输出控制和自动平衡泵在广泛的范围内 包括运动在内的生理条件，b）检查设备的生物相容性 评估血栓形成，血栓栓塞，von Willebrand因子降解和 肠血管增生。我们将研究脉动和非脉动模式。