Self-regulating continuous-flow total artificial heart

 描述(申请人提供)：在过去的5年里，连续流量(CF)旋转泵已经取代了体积排量脉动流量泵，因为它们简单、机械可靠性更高、耐用性更好、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)都是容量排出式脉动流量泵，在体积和耐用性方面都有很大的局限性。为了应对这些限制，克利夫兰诊所一直在根据当前NIH资助的计划(R01 HL096619)开发一种独特的、无阀和无传感器的诱导脉冲CFTAH。它有一个单一的，连续旋转的无刷直流电机和泵组件，在转子的两端都有一个离心泵。该泵在没有传感器的情况下被动地平衡左、右心房压力，并且足够小(直径6.6厘米，长9.8厘米)，适合小型患者。最近，在没有抗凝治疗的情况下进行的连续三次小牛实验表明，在任何器官中都没有血栓栓塞症，具有出色的生物相容性。这些动物保持健康，并按计划在30天或90天的时间内被处死，这是目前世界上单活动部分TAH植入时间最长的记录。这项竞争性更新申请的目标是(1)通过实施从先前计划中吸取的经验教训来改进和完善当前的CFTAH设计，(2)开发一种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)利用这一理想的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标是：(1)结合临床和行业专家的意见和CFD分析，分析系统需求并改进泵设计，以进一步提高生物相容性、固有的液压泵调节性、耐用性和自动流量控制。(2)开发和评估实时CPM，使用功率和力平衡的转子位置信号来估计泵流量、体肺压力梯度和血管阻力、入口压差、左和/或右吸力及其严重程度，以及近端堵塞。 (3)完成系统性能和临床相关操作范围的溶血水平的体外验证，(4)完成体内动物实验，以验证血流动力学响应、生物兼容性、自我调节机械设计和自动速度控制，以及(5)通过进行体内脉动研究，评估无脉搏或脉搏减少对血流动力学响应和病理生理学的影响。该项目的成功完成将证明这项CFTAH技术的安全性和有效性，为技术转让做好准备，并最终为临床医生提供治疗双室心衰患者的宝贵选择，这也是该项目的目标。

 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.