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（由适用提供）：在过去的5年中，连续流动泵（CF）旋转泵由于其简单性，机械可靠性提高，提高耐用性，较小的尺寸和更好的结果而取代了体积 - 置换脉冲流动泵。与左心室辅助设备（LVAD）相比，现有的临床人造心脏（TAH）都是体积 - 置换脉冲流泵，并且它们的尺寸和耐用性大大限制。为了应对这些局限性，克利夫兰诊所一直在开发一个独特的，valveless和无传感器的CFTAH，并在当前NIH资助的计划（R01 HL096619）下引起脉冲。它具有单个连续旋转的无刷直流电动机和泵组件，并在转子的两端带一个离心泵。泵可以被动地平衡没有传感器的左右心房压力，并且足够小（直径为6.6厘米，长度为9.8厘米）适合小型患者。没有抗凝治疗的最新三个连续的小腿实验表现出出色的生物相容性，任何组织中没有血小板主义。这些动物保持健康，并在计划的30或90天的计划期间被处死，这是当前的世界记录，植入持续时间最长，因为TAH具有单个移动部分。该竞争性更新应用的目标是（1）通过实施从先前计划中学到的经验教训，（2）开发新的连续患者监护仪（CPM）来改善和完善当前的CFTAH设计，以增强血液动力学和泵送信息的实时输出，并（3）研究该理想实验性实验性的Pulsetity对Pulsetity of Pulsetity a效果的影响。实现这些目标的具体目的是（1）通过临床和行业专家和CFD分析的投入来分析系统要求并完善泵设计，以进一步提高生物相容性，固有的Hydrofluic泵调节，耐用性和自动流量控制。 （2）使用功率和力平衡的转子位置信号来开发和评估实时CPM，以估计泵流，全身和肺压力梯度以及血管电阻，入口压力差，左和/或右假设及其严重性及其严重性，以及与阻止 泵，（3）在临床上相关的操作范围内对系统性能和溶血水平进行完整的体外验证，（4）完整的体内动物实验，以验证血液动力学响应，生物相容性，机械设计和自动速度控制以及（5）通过对脉搏的脉冲响应的效果对血液动力学响应的效果以及（5）通过对血液动力学的效果进行效果，以进行血液动力学的效果。该计划的成功完成将证明该CFTAH技术的安全性和有效性，使其为技术转移做好准备，并最终为临床医生提供了对双脑脑衰竭患者的宝贵治疗选择，这是该项目的目标。