Cavopulmonary Assist: Circulatory Support for Fontan Circulation

描述（由申请人提供）：治疗单个功能性心室无疑是一个重大的医疗挑战。它是在生命第一年因任何出生缺陷而死亡的主要原因。那些幸免于难的人却面临着无法直接治疗的终身残疾，这构成了一个新出现的公共卫生问题。目前，修复是在一系列复杂的3阶段操作中进行的，这些操作以不稳定和死亡率而闻名。这是由于使用全身动脉分流术为新生儿提供肺血流的实质性来源。修复的终点是单心室Fontan循环，其中腔静脉与肺动脉相连。由于没有右侧心室动力源，静脉回流被严重改变，单心室充盈不理想。我们从理论上认为，适度增加现有Fontan腔室肺流量（6-8 mmHg）的方法可以通过再现更稳定的双心室生理并允许稳定和/或压缩手术阶段来解决这些问题。逐渐减少支持将允许适应系统静脉源独立灌注肺部所需的更高压力（10- 15mmhg）。在腔隙肺连接复杂的四向血流解剖中提供低压支持的血泵的功能参数明显不同于任何其他循环辅助应用：目前还没有这样的泵存在。我们假设，在冯·卡门粘性泵的基础上，驱动器盘泵是提供腔室肺辅助的最佳选择。只有一个叶轮，基于导管的可膨胀旋转盘在4个相反的方向上提供首选的低压、大容量流量，而不会有静脉通路阻塞的风险。为了发展这一突破性的创新，我们的具体目标是：1)在3路“T”型和4路“T”型腔隙肺连接中，描述由中心稳定体（致动器盘）旋转引起的上游、局部和下游流动模式；2)通过先进的数值模拟和流动可视化，确定双锥形可膨胀旋转叶轮的最佳几何和表面特征，以增强腔隙肺流量；通过模拟血流环、血流可视化和溶血研究的体外反馈，旋转盘泵的血栓形成性能，4)证明了经皮粘性泵在单室Fontan循环动物模型中的支持作用。我们将通过交叉专业知识来实现这些目标：计算流体动力学建模；表面简化;流可视化;体外造模；生理控制;thrombogenicity;弹性体的化学;镍钛诺冶金;microcoil制造;导管一次性用品;旋转血泵设计；原型设计;并在体内进行临床研究。完成后，一种易于实施的经皮技术将显著改善丰坦的循环状态，作为一种预估设备交付临床使用。对于有单心室Fontan循环的患者，无论是年轻人还是老年人，这种安全、简单、可靠的增加腔室肺流量的方法将解决他们尚未解决的健康需求。

DESCRIPTION (provided by applicant): Treatment of single functional ventricle is indisputably a significant healthcare challenge. It is the leading cause of death from any birth defect in the first year of life. Those who are fortunate to survive face lifelong disability for which there is no direct therapy, constituting an emerging public health concern. Currently, repair is performed in a complex series of 3 staged operations which are notorious for instability and mortality. This is attributable to the use of a systemic arterial shunt to provide a substantive source of pulmonary blood flow in the neonate. The endpoint of repair is a univentricular Fontan circulation, in which the vena cavae are connected to the pulmonary artery. Because there is no right-sided ventricular power source, venous return is profoundly altered and filling of the single ventricle is suboptimal. We have theorized that a means to modestly augment existing Fontan cavopulmonary flow (6-8 mmHg) would address these problems by reproducing more stable two-ventricle physiology and permitting stabilization and/or compression of surgical stages. Gradual reduction in support would permit adaptation to the higher pressure needed (10-15 mmHg) for a systemic venous source to independently perfuse the lungs. The functional parameters for a blood pump to provide low- pressure support in the complex 4-way flow anatomy of a cavopulmonary connection are markedly dissimilar to any other circulatory assist application: No such pump currently exists. We hypothesize that an actuator disk pump, based on the von Karman viscous pump, is optimal to provide cavopulmonary assist. With only one impeller, a catheter-based expandable rotary disk provides the preferred low-pressure, high-volume flow in 4 opposing directions without risk of venous pathway obstruction. To develop this breakthrough innovation, our specific aims are to: 1) characterize the upstream, local, and downstream flow patterns induced by rotation of a central stabilizing body (actuator disk) within a 3-way "T" and 4-way "t" cavopulmonary connection, 2) define the optimal geometric and surface characteristics of a bi-conical expandable rotary impeller to augment cavopulmonary flow using advanced numerical modeling and flow visualization, 3) optimize the hemodynamic, biocompatibility, and thrombogenicity performance of a rotary disk pump through in vitro feedback from mock flow loop, flow visualization, and hemolysis studies, 4) demonstrate percutaneous viscous pump support in an animal model of univentricular Fontan circulation. We will accomplish these aims by intersecting expertise in: computational fluid dynamic modeling; surface streamlining; flow visualization; in vitro modeling; physiologic control; thrombogenicity; elastomer chemistry; nitinol metallurgy; microcoil fabrication; catheter disposables; rotary blood pump design; prototyping; and clinically rooted in vivo studies. At completion, an easily implemented percutaneous technology which dramatically improves Fontan circulatory status will be delivered as a predicate device to clinical use. In patients with univentricular Fontan circulations - young and old - this safe, simple, and reliable method to augment cavopulmonary flow will address their unresolved health needs.