Cavopulmonary Assist to Reverse the Fontan

腔肺辅助逆转 Fontan

基本信息

批准号：
10464980
负责人：
MARK D RODEFELD
金额：
$ 233.98万
依托单位：
INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-14 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10464980
关键词：
Address Adult Anatomy Animal Model Assisted Circulation Biomechanics Biomedical Engineering Blood Circulation Blood flow Cardiac Output Caring Cause of Death Cessation of life Chronic Clinical Research Common Ventricle Complex Congenital Abnormality Data Disease Electromagnetics Environment Event Failure Functional disorder Geometry Goals Health Healthcare Hemolysis In Vitro Life Liquid substance Lung Maintenance Mission Motor Nature Obstruction Operative Surgical Procedures Pathologic Pathway interactions Patients Performance Physiological Physiology Power Sources Preventive therapy Public Health Pulmonary Circulation Pulmonary artery structure Pump Residual state Risk Rotation Self-Help Devices Series Single ventricle congenital heart disease Survivors Syndrome Technology Testing Therapeutic United States National Institutes of Health Venous Venous Pressure level Ventricular base biomaterial compatibility blood pump curative treatments disability hemodynamics improved in vivo in vivo evaluation innovation innovative technologies insight mechanical circulatory support operation palliate palliation palliative pressure prevent prototype repaired technology development thrombogenesis treatment strategy

Address Adult Anatomy Animal Model Assisted Circulation Biomechanics Biomedical Engineering Blood Circulation Blood flow Cardiac Output Caring Cause of Death Cessation of life Chronic Clinical Research Common Ventricle Complex Congenital Abnormality Data Disease Electromagnetics Environment Event Failure Functional disorder Geometry Goals Health Healthcare Hemolysis In Vitro Life Liquid substance Lung Maintenance Mission Motor Nature Obstruction Operative Surgical Procedures Pathologic Pathway interactions Patients Performance Physiological Physiology Power Sources Preventive therapy Public Health Pulmonary Circulation Pulmonary artery structure Pump Residual state Risk Rotation Self-Help Devices Series Single ventricle congenital heart disease Survivors Syndrome Technology Testing Therapeutic United States National Institutes of Health Venous Venous Pressure level Ventricular base biomaterial compatibility blood pump curative treatments disability hemodynamics improved in vivo in vivo evaluation innovation innovative technologies insight mechanical circulatory support operation palliate palliation palliative pressure prevent prototype repaired technology development thrombogenesis treatment strategy

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项目摘要

The 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 survive through completion of Fontan repair have chronic circulatory inefficiency and a lifelong risk of failure for which there is no preventive therapy. As more survivors reach adulthood, late Fontan failure and attrition has become a public health concern. As a clear reflection of its palliative nature, survival 30 years after Fontan is 43-70%. In a univentricular Fontan circulation, the vena cavae are connected directly to the pulmonary artery, placing the systemic and pulmonary circulations in a stable series arrangement. But, there is no subpulmonary power source to pump blood through the lungs. As a result, systemic venous pressure is pathologically elevated and preload to the single ventricle is reduced; combined, these factors form the basis of the Fontan paradox. Survivors are trapped for the remainder of their lives in a syndromic cycle of chronic debilitating disease that has no known solution. We have theorized that a means to replace the missing subpulmonary power source by modestly augmenting existing Fontan cavopulmonary flow (~6-8 mmHg) will address these problems. By replacing what is missing, the Fontan circulation can be reversed to a more stable two-ventricle physiology, producing physiologic cure. The biomechanical parameters for a blood pump to function 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 anatomically-specific pump, based on the von Karman viscous pump, is an optimal solution to assist cavopulmonary flow. A single impeller will provide low-pressure, high-volume cavopulmonary blood flow augmentation in 4 opposing directions with no risk of venous pathway obstruction. In the event of rotational failure, the pump will default to serve as a relatively innocuous passive flow diverter in an unsupported Fontan. To develop this breakthrough innovation, our specific aims are to: 1) perform electromechanical optimization of a Fontan viscous pump; 2) perform biocompatibility optimization of a Fontan viscous pump via hemolysis and thrombogenicity studies; 3) perform durability and chronic in vivo testing of a Fontan viscous pump in an animal model of Fontan circulation. We will accomplish these aims by intersecting expertise in computational fluid dynamics; hydraulics; electromagnetics; rotordynamics; tribology; in vitro mock loop testing; thrombogenicity testing; and in vivo studies. Pilot data in an advanced prototype demonstrate compelling feasibility of this technology to improve circulatory status by permanently reversing the Fontan paradox. A permanently implantable Fontan blood pump will usher in a new era in single ventricle care. By simply replacing what is missing, it will enable the ultimate exit strategy for single ventricle heart disease: biventricular health.

单个功能性心室的治疗无疑是一项重大的医疗挑战。这是领导生命第一年的任何出生缺陷导致死亡原因。那些能够通过fontan完成的人维修具有慢性循环效率和没有预防疗法的终生失败风险。随着越来越多的幸存者成年，后期的Fontan失败和流失已成为公共卫生的关注。作为明确反映了其姑息性的性质，丰丹30年后的生存率为43-70％。在一个室室中循环，腔腔直接连接到肺动脉，放置全身和肺动脉稳定系列的循环。但是，没有肺部电源来抽血通过肺部。结果，系统性静脉压在病理上升高，并预紧至单个心室减少；这些因素结合在一起，构成了方坦悖论的基础。幸存者被困他们的剩余生命中没有已知解决方案的慢性衰弱疾病综合征。我们已经理论上，通过适度扩大来替换缺失的亚肺电源源的手段现有的Fontan Cavopulonary流（〜6-8 mmHg）将解决这些问题。通过更换缺少的东西， Fontan循环可以逆转为更稳定的两种换腔生理学，从而产生生理治疗。血泵的生物力学参数，以在A Cavopulonary连接与任何其他循环辅助应用明显不同：没有这样的泵目前存在。我们假设一个基于von Karman粘性泵的解剖学特异性泵，是有助于腔流量流的最佳解决方案。单个叶轮将提供低压的大量在4个相对方向上的腔肺血流增加，没有静脉途径阻塞的风险。如果发生旋转故障，泵将默认为相对无害的被动流动器的分流一个不受支持的丰丹。为了发展这一突破性创新，我们的具体目的是：1）执行 Fontan粘性泵的机电优化； 2）执行Fontan的生物相容性优化通过溶血和血栓形成研究粘性泵； 3）执行耐用性和慢性体内测试方坦循环动物模型中的fontan粘性泵。我们将通过相交来实现这些目标计算流体动力学方面的专业知识；液压；电磁学；动力学；摩擦学;体外模拟循环测试；血栓形成性测试；和体内研究。高级原型中的试验数据证明了这项技术的可行性通过永久逆转Fontan来提高循环状态悖论。永久性植入的丰坦血泵将在单个心室护理中引入一个新时代。经过只需替换缺少的东西，它就会实现单个心室心脏病的最终退出策略：双室健康。