Self-regulating continuous-flow total artificial heart

自调节连续流全人工心脏

• 批准号: 9316685
• 负责人: Kiyotaka Fukamachi
• 金额: $ 132.91万
• 依托单位: CLEVELAND CLINIC LERNER COM-CWRU
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9316685
• 关键词: Achievement; Affect; Animal Experiments; Animals; Anticoagulation; Aortic Valve Insufficiency; Body Surface Area; Caliber; Cardiovascular system; Clinic; Clinical; Devices; Effectiveness; Equilibrium; Failure; France; Functional disorder; Funding; Future; Gastrointestinal Hemorrhage; Goals; Healthcare; Heart Atrium; Heart Transplantation; Heart failure; Hemolysis; Implant; In Vitro; Incidence; Industry; Informal Social Control; Left; Length; Lung; Mechanics; Modeling; Motor; Organ; Outcome; Output; Patient Monitoring; Patients; Performance; Physiologic pulse; Physiological; Positioning Attribute; Pulsatile Flow; Pump; Regulation; Safety; Severities; Signal Transduction; Source; Speed; Suction; System; Technology; Technology Transfer; Testing; Thromboembolism; Thrombosis; Time; United States National Institutes of Health; Validation; Vascular resistance; Ventricular; base; biomaterial compatibility; clinically relevant; design; experimental study; hemodynamics; implantable device; improved; in vivo; left ventricular assist device; mortality; operation; pressure; programs; public health relevance; response; sensor; total artificial heart

 DESCRIPTION (provided by applicant): In the past 5 years, continuous-flow (CF) rotary pumps have replaced volume-displacement pulsatile-flow pumps because of their simplicity, increased mechanical reliability, improved durability, smaller size, and better outcomes. In contrast to left ventricular assist devices (LVADs), existing clinical total artificial hearts (TAH) are all volume-displacement pulsatile-flow pumps, and they have significant limitations in their large size and durability. In response to these limitations, Cleveland Clinic has been developing a unique, valveless, and sensorless CFTAH with induced pulse under the current NIH-funded program (R01 HL096619). It has a single, continuously rotating, brushless DC motor and pump assembly with a centrifugal pump on both ends of the rotor. The pump passively balances left and right atrial pressures without sensors and is small enough (6.6 cm in diameter and 9.8 cm in length) to fit in small patients. The most recent, three consecutive calf experiments, conducted with no anticoagulation therapy, demonstrated outstanding biocompatibility with no thromboembolism in any organs. The animals remained healthy and were sacrificed at the planned duration of 30 or 90 days, which is the current world's record for longest duration of implant for a TAH with a single moving part. The objectives of this competitive renewal application are (1) to improve and refine the current CFTAH design by implementing the lessons learned from the prior program, (2) to develop a new continuous patient monitor (CPM) to enhance the real-time output of hemodynamic and pump information, and (3) to study the effects of pulsatility on pathophysiology with this ideal experimental platform. Specific aims to achieve these objectives are (1) Analyze the system requirements and refine the pump design, with input from clinical and industry experts and CFD analysis, to further improve biocompatibility, inherent hydraulic pump regulation, durability, and automatic flow control. (2) Develop and evaluate the real-time CPM using power and force- balanced rotor position signals to estimate pump flow, systemic and pulmonary pressure gradients and vascular resistances, inlet pressure difference, left and/or right suction and its severity, and blockage proximal to the pump, (3) Complete in vitro validation of system performance and level of hemolysis over the clinically relevant range of operation, (4) Complete in vivo animal experiments to validate hemodynamic response, biocompatibility, self-regulating mechanical design, and automatic speed control, and (5) Evaluate the effects of nonpulse or reduced pulse on hemodynamic response and pathophysiology with the same device by performing in vivo pulsatility studies. The successful completion of this program will demonstrate the safety and effectiveness of this CFTAH technology, making it ready for technology transfer, and ultimately providing clinicians with a valuable treatment option for patients with biventricular heart failure, which is the goal o this project.

 描述（由申请人提供）：在过去的5年中，连续流（CF）旋转泵已经取代容积排量脉动流泵，因为它们简单，机械可靠性增加，耐用性提高，尺寸更小，效果更好。与左心室辅助装置（LVAD）相比，现有的临床全人工心脏（TAH）都是容积排量脉动流泵，并且它们在其大尺寸和耐用性方面具有显著限制。为了应对这些局限性，Cleveland Clinic在当前NIH资助的项目（R 01 HL 096619）下开发了一种独特的、无阀、无传感器的CFTAH（带诱导脉冲）。它有一个单一的，连续旋转，无刷直流电机和泵组件与离心泵两端的转子。该泵在没有传感器的情况下被动地平衡左心房和右心房压力，并且足够小（直径6.6 cm，长度9.8 cm）以适合身材矮小的患者。最近的三个连续小牛实验，在没有抗凝治疗的情况下进行，证明了出色的生物相容性，在任何器官中都没有血栓栓塞。动物保持健康，并在计划的30天或90天内处死，这是目前世界上具有单个活动部件的TAH植入时间最长的记录。本竞争性更新申请的目的是（1）通过实施从先前项目中吸取的经验教训来改进和完善当前CFTAH设计，（2）开发新的连续患者监护仪（CPM）以增强血流动力学和泵信息的实时输出，以及（3）使用此理想实验平台研究脉动性对病理生理学的影响。实现这些目标的具体目的是（1）分析系统要求并完善泵设计，并从临床和行业专家以及CFD分析中获得输入，以进一步改善生物相容性、固有液压泵调节、耐用性和自动流量控制。(2)使用功率和力平衡转子位置信号开发和评估实时CPM，以估计泵流量、全身和肺动脉压差和血管阻力、入口压差、左和/或右抽吸及其严重程度以及近端阻塞。 泵，（3）在临床相关操作范围内完成系统性能和溶血水平的体外验证，（4）完成体内动物实验以验证血液动力学反应、生物相容性、自调节机械设计和自动速度控制，以及（5）通过进行体内脉动试验，评价无脉动或脉动减少对相同器械的血流动力学反应和病理生理学的影响问题研究该项目的成功完成将证明该CFTAH技术的安全性和有效性，使其为技术转让做好准备，并最终为临床医生提供有价值的双心室心力衰竭患者治疗选择，这是该项目的目标。