Cavopulmonary Assist: Circulatory Support for the Univentricular Fontan Circulat

描述(由申请人提供)：单功能脑室的治疗无疑是一个重大的医疗挑战。它是导致出生第一年任何出生缺陷死亡的主要原因。那些幸存下来的人面临终身残疾，没有直接的治疗方法，构成了一个新的公共卫生问题。目前，修复是通过一系列复杂的3个阶段性手术进行的，这些手术以不稳定和死亡率而臭名昭著。这归因于使用全身动脉分流来为新生儿提供实质性的肺血流来源。修复的终点是单室Fontan循环，其中腔静脉连接到肺动脉。由于没有右侧脑室的动力源，静脉回流发生了深刻的变化，单脑室的充盈也不是最理想的。我们推测，适度增加现有Fontan腔静脉肺流量(6-8毫米汞柱)的方法将通过复制更稳定的双心室生理并允许手术阶段的稳定和/或压缩来解决这些问题。逐渐减少支持将允许适应所需的较高压力(10-15毫米汞柱)，以便全身静脉来源独立地对肺进行灌流。血泵在腔静脉-肺连接复杂的四向流动解剖中提供低压支持的功能参数与任何其他循环辅助应用明显不同：目前还不存在这样的泵。我们假设，在von Karman粘性泵的基础上，执行机构盘式泵是提供腔肺辅助的最佳选择。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、大流量流动，而不存在静脉通路阻塞的风险。为了开发这项突破性的创新，我们的具体目标是：1)表征在3向“T”和4向“T”腔肺连接中由中央稳定体(执行机构盘)旋转引起的上游、局部和下游流动模式，2)使用先进的数值建模和流动显示来确定用于增强腔肺流动的双锥形可膨胀旋转叶轮的最佳几何和表面特征，3)通过模拟流环、流动可视化和溶血研究的体外反馈来优化旋转盘式泵的血流动力学、生物相容性和血栓形成性能，4)在单室Fontan循环的动物模型中演示经皮粘性泵支持。我们将通过交叉以下领域的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；镍钛冶金；微线圈制造；导管一次性；旋转式血泵设计；原型制作；临床扎根体内研究。完成后，一种易于实施的、显著改善方坦循环状况的经皮技术将作为一种预测性设备交付临床使用。对于单室Fontan循环的患者，无论是年轻人还是老年人，这种安全、简单和可靠的增加腔肺血流的方法将满足他们尚未解决的健康需求。 公共卫生意义：我们将开发一种血泵，用于在单室Fontan循环中提供腔肺辅助。这将极大地改善出生时患有单心室心脏病的儿童和成人的医疗保健。

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. PUBLIC HEALTH RELEVANCE: We will develop a blood pump designed to provide cavopulmonary assist in a univentricular Fontan circulation. This will dramatically improve the healthcare of children and adults born with single ventricle heart disease.