Cavopulmonary Assist: Circulatory Support for the Univentricular Fontan Circulat

腔静脉辅助：单心室 Fontan 循环的循环支持

• 批准号: 7988940
• 负责人: MARK D RODEFELD
• 金额: $ 51.07万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7988940
• 关键词: Acute; Address; Adult; Anatomy; Animal Model; Assisted Circulation; Biomechanics; Blood Circulation; Blood Vessels; Blood flow; Cardiac Output; Cardiopulmonary Bypass; Catheters; Cause of Death; Characteristics; Chemistry; Child; Chronic; Clinical; Common Ventricle; Complex; Congenital Abnormality; Data; Defect; Dependence; Devices; Disease; Elastomers; Environment; Equilibrium; Face; Failure; Feedback; Goals; Health; Healthcare; Heart Diseases; Hemolysis; Human; Hypoplastic Left Heart Syndrome; Hypoxemia; Imagery; In Vitro; Left ventricular structure; Life; Liquid substance; Lung; Lung diseases; Measures; Metallurgy; Methods; Modeling; Neonatal; Newborn Infant; Obstruction; Operative Surgical Procedures; Pathway interactions; Patients; Pattern; Performance; Physiological; Physiology; Plant Roots; Power Sources; Procedures; Public Health; Pulmonary Circulation; Pulmonary Vascular Resistance; Pulmonary artery structure; Pump; Right ventricular structure; Risk; Rotation; Series; Shunt Device; Side; Solutions; Source; Staging; Surface; Survivors; Technology; Testing; Time; Vena caval structure; Venous; Venous Pressure level; Ventricular; base; biomaterial compatibility; blood pump; design; disability; hemodynamics; improved; in vitro Model; in vivo; innovation; insight; mortality; neonate; nitinol; normotensive; operation; pressure; public health relevance; repaired; treatment strategy; vascular bed

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.

描述（由申请人提供）：单个功能性心室的治疗无疑是一个重大的医疗挑战。这是生命第一年中任何出生缺陷导致死亡的主要原因。那些幸运的人面对没有直接治疗的终身残疾，构成新兴的公共卫生问题。当前，维修是在复杂的3个阶段操作系列中进行的，这些操作因不稳定和死亡而臭名昭著。这归因于使用系统性动脉分流来提供新生儿中肺血流的实质性来源。修复的终点是一个单脑膜的fontan循环，其中腔静脉与肺动脉相连。由于没有右侧的心室电源，因此静脉回流会深刻改变，并且单脑室的填充是次优的。我们的理论是，一种适度地增加现有的方坦腔流量（6-8 mmHg）的方法，可以通过再现更稳定的两种偏见生理学并允许稳定和/或压缩手术阶段来解决这些问题。逐渐减少支撑物将允许适应系统静脉源以独立灌注肺所需的较高压力（10-15 mmHg）。血液泵的功能参数可在复杂的四向流动解剖结构中提供低压支持，这与任何其他循环辅助应用明显不同：目前不存在此类泵。我们假设基于von Karman粘性泵的执行器磁盘泵是提供Cavopulonary辅助的最佳选择。只有一个叶轮，一个基于导管的可扩展旋转盘可在4个相对方向上提供首选的低压，高体积流量，而没有静脉途径阻塞的风险。为了发展这一突破性创新，我们的具体目的是：1）特征表征在三向“ T”和4路“ t”和4向“ t”“ t” t“ t”“ cavopulonary Connection，2）中旋转中央稳定体（执行器磁盘）引起的上游，本地和下游流动模式，2建模和流动可视化，3）优化旋转盘泵的血液动力学，生物相容性和血栓形成性能通过模拟流动环，流动可视化和溶血研究的体外反馈，4）表现出经皮粘性粘液泵在单脑膜循环的动物模型中的经皮粘性泵。我们将通过与以下方面的专业知识相交来实现这些目标：计算流体动态建模；表面精简；流动可视化；体外建模；生理控制；血栓形成；弹性体化学；硝基冶金；微型机构制造；导管一次性装置；旋转血泵设计；原型并在临床上植根于体内研究。完成后，一种易于实施的经皮技术，可以将Fontan循环状态大大改善，作为临床使用的谓词装置。对于单脑室循环的患者（年轻人和老年），这种安全，简单且可靠的方法来增加腔流失流的方法将满足其未解决的健康需求。 公共卫生相关性：我们将开发一个旨在为单脑室方坦循环提供辅助辅助的血泵。这将显着改善患有单脑室心脏病的儿童和成人的医疗保健。