Cavopulmonary Assist: Circulatory Support for Fontan Circulation

描述（由申请人提供）：单功能心室的治疗无疑是一项重大的医疗挑战。它是导致出生后第一年内任何出生缺陷死亡的主要原因。那些幸运地幸存下来的人面临终身残疾，没有直接的治疗方法，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阶段手术中进行的，这些手术因不稳定和死亡率而臭名昭著。这是由于使用了全身动脉分流，为新生儿提供了大量的肺血流来源。修复的终点是单心室Fontan循环，其中腔静脉与肺动脉相连。由于没有右侧心室电源，静脉回流发生了深刻的变化，单心室的充盈不理想。我们的理论是，适度增加现有Fontan腔静脉流量（6-8 mmHg）的方法将通过重现更稳定的双心室生理学并允许手术阶段的稳定和/或压缩来解决这些问题。支持的逐渐减少将允许适应全身静脉源独立灌注肺所需的较高压力（10-15 mmHg）。用于在腔静脉连接的复杂4路流动解剖结构中提供低压支持的血泵的功能参数与任何其他循环辅助应用明显不同：目前不存在这样的泵。我们假设，一个致动器盘泵，冯卡门粘性泵的基础上，是最佳的，以提供空腔辅助。只有一个叶轮，基于导管的可膨胀旋转盘在4个相反方向上提供优选的低压、高容量流量，而没有静脉通路阻塞的风险。为了开发这一突破性创新，我们的具体目标是：1）表征由中心稳定体的旋转引起的上游、局部和下游流型（致动器盘）在3向“T”和4向“t”空腔连接内，2）定义双金属的最佳几何和表面特征，使用先进的数值模拟和流动可视化技术，使用锥形可膨胀旋转叶轮来增强腔静脉流动，3）优化血液动力学，生物相容性，通过模拟流动回路、流动可视化和溶血研究的体外反馈，旋转圆盘泵的血栓形成性能，4）证明了单心室Fontan循环动物模型中的经皮粘性泵支持。我们将通过以下领域的交叉专业知识来实现这些目标：计算流体动力学建模;表面流线化;流动可视化;体外建模;生理控制;血栓形成;弹性体化学;镍钛合金冶金;微弹簧圈制造;导管一次性用品;旋转血泵设计;原型设计;以及临床植根于体内的研究。完成时，一种可显著改善Fontan循环状态的易于实施的经皮技术将作为同品种器械交付临床使用。对于单心室Fontan循环的患者（年轻和老年），这种安全、简单和可靠的增加腔静脉血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.