Cavopulmonary Assist to Reverse the Fontan

腔肺辅助逆转 Fontan

• 批准号: 10263146
• 负责人: MARK D RODEFELD
• 金额: $ 233.66万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 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/10263146
• 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; Heart Diseases; Hemolysis; In Vitro; Life; Liquid substance; Lung; Maintenance; Mechanics; 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; 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; operation; palliate; palliation; palliative; pressure; prevent; prototype; repaired; technology development; thrombogenesis; treatment strategy

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.

单功能心室的治疗无疑是一个重大的医疗挑战。它是领先的 出生第一年因任何出生缺陷而死亡的原因。那些在 Fontan 完成后幸存下来的人 修复具有慢性循环效率低下和终生失败的风险，而没有预防性治疗。 随着越来越多的幸存者成年，晚期丰坦衰竭和自然消耗已成为一个公共卫生问题。作为一个 Fontan 后 30 年的生存率为 43-70%，清楚地反映了其姑息性质。在单心室 Fontan 中 在血液循环中，腔静脉直接与肺动脉相连，将全身和肺动脉置于 以稳定的系列排列进行循环。但是，没有肺下动力源来泵血 通过肺部。结果，全身静脉压病理性升高并预负荷至单个 心室缩小；这些因素结合起来，构成了丰坦悖论的基础。幸存者被困 他们的余生都处于慢性衰弱性疾病的综合症循环中，而且没有已知的解决方案。 我们的理论是，有一种方法可以通过适度增强来替代缺失的肺下动力源 现有的 Fontan 腔静脉肺流量 (~6-8 mmHg) 将解决这些问题。通过替换缺失的东西， Fontan 循环可以逆转为更稳定的两心室生理，从而产生生理治愈。 血泵在复杂的四向流动解剖结构中发挥作用的生物力学参数 腔肺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。我们假设基于冯卡门粘性泵的解剖学特定泵， 是辅助腔静脉肺血流的最佳解决方案。单个叶轮将提供低压、高流量 4 个相反方向的腔肺血流增加，没有静脉通路阻塞的风险。 如果发生旋转故障，泵将默认充当相对无害的被动分流器 无支撑的 Fontan。为了开发这一突破性创新，我们的具体目标是：1) Fontan 粘性泵的机电优化； 2) 对 Fontan 进行生物相容性优化 通过溶血和血栓形成研究进行粘性泵； 3）进行耐久性和长期体内测试 Fontan 循环动物模型中的 Fontan 粘性泵。我们将通过交叉来实现这些目标 计算流体动力学方面的专业知识；液压系统；电磁学；转子动力学；摩擦学;体外模拟 循环测试；血栓形成测试；和体内研究。先进原型中的试点数据演示 该技术通过永久逆转 Fontan 来改善循环状态具有令人信服的可行性 悖论。永久植入式 Fontan 血泵将开创单心室护理的新时代。经过 只需更换缺失的部分，就可以实现单心室心脏病的最终退出策略： 双心室健康。