Functional restoration of ventriculo-arterial coupling in cardiogenic shock via dual mechanical support

通过双机械支撑恢复心源性休克心室-动脉耦合的功能

• 批准号: 10491278
• 负责人: Steven Paul Keller
• 金额: $ 17.06万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-10 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10491278
• 关键词: Adopted; Advanced Development; Advisory Committees; Affect; Animal Experiments; Aorta; Area; Blood; Blood Vessels; Blood flow; Cardiac; Cardiogenic Shock; Cardiovascular Physiology; Caring; Cessation of life; Characteristics; Charge; Circulation; Clinical; Clinical Research; Clinical Sciences; Computer Models; Coupling; Critical Care; Device Designs; Devices; Disease Progression; Distal; Engineering; Equilibrium; Extracorporeal Membrane Oxygenation; Family suidae; Five-Year Plans; Gases; Harm Reduction; Heart; Human; Image; Impairment; Left; Left Ventricular Function; Left ventricular structure; Life; Link; Liquid substance; Location; Maps; Measurement; Mechanics; Medical; Mentors; Metabolic; Methods; Modality; Modeling; Multiple Organ Failure; Organ; Organ failure; Outcome; Patient-Focused Outcomes; Patients; Perfusion; Physicians; Physiological; Pulmonary Heart Disease; Pump; Recovery; Reporting; Research; Research Personnel; Research Training; Residual state; Services; Shock; Shunt Device; Stroke; System; Technology; Thrombus; Time; Titrations; Trees; United States National Institutes of Health; Velocimetries; Venous; Ventricular; career; femoral artery; functional restoration; heart circulation; heart function; heart metabolism; hemodynamics; improved; improved outcome; in silico; insight; interest; mechanical circulatory support; multimodality; operation; particle; porcine model; preservation; programs; ventricular assist device; Adopted; Advanced Development; Advisory Committees; Affect; Animal Experiments; Aorta; Area; Blood; Blood Vessels; Blood flow; Cardiac; Cardiogenic Shock; Cardiovascular Physiology; Caring; Cessation of life; Characteristics; Charge; Circulation; Clinical; Clinical Research; Clinical Sciences; Computer Models; Coupling; Critical Care; Device Designs; Devices; Disease Progression; Distal; Engineering; Equilibrium; Extracorporeal Membrane Oxygenation; Family suidae; Five-Year Plans; Gases; Harm Reduction; Heart; Human; Image; Impairment; Left; Left Ventricular Function; Left ventricular structure; Life; Link; Liquid substance; Location; Maps; Measurement; Mechanics; Medical; Mentors; Metabolic; Methods; Modality; Modeling; Multiple Organ Failure; Organ; Organ failure; Outcome; Patient-Focused Outcomes; Patients; Perfusion; Physicians; Physiological; Pulmonary Heart Disease; Pump; Recovery; Reporting; Research; Research Personnel; Research Training; Residual state; Services; Shock; Shunt Device; Stroke; System; Technology; Thrombus; Time; Titrations; Trees; United States National Institutes of Health; Velocimetries; Venous; Ventricular; career; femoral artery; functional restoration; heart circulation; heart function; heart metabolism; hemodynamics; improved; improved outcome; in silico; insight; interest; mechanical circulatory support; multimodality; operation; particle; porcine model; preservation; programs; ventricular assist device

PROJECT SUMMARY Cardiogenic shock is a highly morbid condition - impaired heart function leads to multi-organ failure and death. Even prompt medical therapy is frequently insufficient and mechanical means of supporting the circulation are increasingly evolving. Extracorporeal membrane oxygenation (ECMO) has rapidly been embraced to provide mechanical circulatory support but limited understanding of its impact on left ventricular function restricts its use. ECMO profoundly disrupts coupling between the left ventricle and the arterial system through introduction of retrograde perfusion that collides with antegrade blood flow from the failing heart to generate a dynamic watershed region whose impact on end-organ perfusion and clinical outcomes is unknown. Recent clinical studies report improved outcomes for ECMO patients when paired with a percutaneous ventricular assist device (pVAD) to provide for dual mechanical support. Intriguingly this idea mirrors our own clinical observations in which addition of a pVAD allows for offloading of the left ventricle and improved clinician control of perfusion. We recently harnessed metrics of interactions between the heart (host) and pVAD (device) in cardiogenic shock to provide insight into the physiological state of the failing heart and parameters that can be utilized to track changes in organ function. We have linked pVAD support to ECMO and have discovered that changes in pVAD operation identify organ recovery or disease progression. We have further investigated the effects of ECMO on blood flow utilizing computational fluid dynamic modeling to quantify flow disruptions induced by the introduction of retrograde perfusion. We hypothesize that dynamic watershed regions affect end-organ perfusion and that pVADs allow for clinician- controlled modulation of the circulation thereby functionally restoring ventriculo-arterial coupling. We investigate this hypothesis by: (1) determining ECMO effects on left ventricular function; (2) quantifying vascular flow dynamics in the ECMO-failing heart circulation; and (3) investigating the effect of dual mechanical support with ECMO and a pVAD on LV function and vascular flow dynamics. We apply multiscale multimodal methods to evaluate our hypothesis. We will study the effects of ECMO and then dual mechanical support on LV function in the intact pig and in studies of patients with cardiogenic shock. We will investigate vascular dynamics utilizing computational fluid dynamics and benchtop models of the ECMO-failing heart circulation. Our findings will yield insight into the application and optimization of ECMO support to improve clinical outcomes and device design. This project makes the most of my clinical interest in shock and mechanical support, engineering background, and research in multiscale pathophysiologic systems. With the guidance of enlightened mentors and an advisory committee, I have developed a five-year plan to provide the didactic and research training I need to become a successful independent investigator focused on the development of advanced mechanical support of end-stage cardiopulmonary disease.

项目摘要 心源性休克是一种高度病态的状况 - 心脏功能受损会导致多器官失败和死亡。 甚至迅速的医疗疗法通常不足以支持循环的机械手段 越来越不断发展。体外膜氧合（ECMO）已迅速接受以提供 机械循环支持，但对其对左心室功能的影响的理解有限，这限制了其使用。 ECMO通过引入左心室和动脉系统之间的耦合 逆行灌注与从失败的心脏流动血流相撞以产生动态 对最终器官灌注和临床结果的影响的分水岭地区尚不清楚。 最近的临床研究报告说，与经皮配对时，ECMO患者的结局改善了 心室辅助装置（PVAD）提供双重机械支撑。有趣的是，这个想法反映了我们自己的 临床观察结果添加PVAD允许左心室和改进的临床医生卸载 控制灌注。我们最近利用了心脏（主机）和PVAD（设备）之间相互作用的指标 在心脏病性休克中，可以深入了解衰竭心脏和参数的生理状态 用于跟踪器官功能的变化。我们已经将PVAD支持与ECMO联系在一起，并发现 PVAD操作的变化确定器官恢复或疾病进展。我们进一步调查了 ECMO利用计算流体动态建模来量化流量破坏引起的血液流动的影响 通过引入逆行灌注。 我们假设动态流域区域会影响最终器官灌注，并且PVADS允许临床医生 - 循环的受控调制，从而在功能上恢复心室 - 动脉耦合。我们调查 该假设通过：（1）确定ECMO对左心室功能的影响； （2）量化血管流动 Ecmo-Failing心脏循环中的动力学； （3）研究双重机械支持的影响 ECMO和PVAD关于LV功能和血管流动动力学。我们将多尺度的多模式方法应用于 评估我们的假设。我们将研究ECMO，然后研究双重机械支持对LV功能的影响 完整的猪和心源性休克患者的研究。我们将研究利用血管动力学 Ecmo-Failing心脏循环的计算流体动力学和台式模型。我们的发现将产生 深入了解ECMO支持的应用和优化，以改善临床结果和设备设计。 该项目充分利用了我对冲击和机械支持，工程背​​景的临床兴趣， 以及多尺度病理生理系统的研究。在开明的导师和咨询的指导下 委员会，我制定了一项五年计划，以提供我成为一个教学和研究培训，我需要成为一个 成功的独立研究者致力于开发终阶段的先进机械支持 心肺疾病。