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

基本信息

  • 批准号:
    10491278
  • 负责人:
  • 金额:
    $ 17.06万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 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

项目摘要

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.
项目概要 心源性休克是一种高度病态的疾病——心脏功能受损会导致多器官衰竭和死亡。 即使及时进行药物治疗也常常是不够的,并且支持循环的机械方法也很有限。 日益发展。体外膜肺氧合(ECMO)已迅速被接受,以提供 机械循环支持,但对其对左心室功能影响的了解有限,限制了其使用。 ECMO 通过引入以下物质,深刻地破坏了左心室和动脉系统之间的耦合 逆行灌注与衰竭心脏的顺行血流碰撞,产生动态 分水岭区域对终末器官灌注和临床结果的影响尚不清楚。 最近的临床研究报告称,当与经皮呼吸机配合使用时,ECMO 患者的预后得到改善 心室辅助装置(pVAD)提供双重机械支持。有趣的是,这个想法反映了我们自己的想法 添加 pVAD 可以减轻左心室负荷并改善临床医生的临床观察 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 在心源性休克中提供对衰竭心脏的生理状态和参数的深入了解 用于跟踪器官功能的变化。我们已将 pVAD 支持与 ECMO 关联起来,并发现 pVAD 操作的变化可确定器官恢复或疾病进展。我们进一步调查了 ECMO 对血流的影响利用计算流体动力学模型来量化引起的血流中断 通过引入逆行灌注。 我们假设动态分水岭区域影响终末器官灌注,并且 pVAD 允许临床医生- 循环的受控调节,从而功能性地恢复心室-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) 量化血管流量 ECMO 失效的心脏循环动态; (3) 研究双机械支撑的效果 ECMO 和 pVAD 对 LV 功能和血管血流动力学的影响。我们应用多尺度多模态方法 评估我们的假设。我们将研究 ECMO 和双机械支撑对 LV 功能的影响 完整的猪以及对心源性休克患者的研究。我们将利用以下方法研究血管动力学 ECMO 失效心脏循环的计算流体动力学和台式模型。我们的研究结果将产生 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。 这个项目充分利用了我对冲击和机械支撑的临床兴趣、工程背景、 和多尺度病理生理系统的研究。在开明导师和顾问的指导下 委员会,我制定了一个五年计划,以提供我成为一名专家所需的教学和研究培训 成功的独立研究者专注于末期先进机械支撑的开发 心肺疾病。

项目成果

期刊论文数量(15)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
COVID-19 patient bridged to recovery with veno-venous extracorporeal membrane oxygenation.
COVID-19 患者通过静脉-静脉体外膜氧合过渡到康复。
  • DOI:
    10.1111/jocs.14829
  • 发表时间:
    2020
  • 期刊:
  • 影响因子:
    1.6
  • 作者:
    Rinewalt,Daniel;Coppolino,Anthony;Seethala,Raghu;Sharma,Nirmal;Salim,Ali;Keller,Steve;Mallidi,HariR
  • 通讯作者:
    Mallidi,HariR
Assessing the SAfety and FEasibility of bedside portable low-field brain Magnetic Resonance Imaging in patients on ECMO (SAFE-MRI ECMO study): study protocol and first case series experience.
  • DOI:
    10.1186/s13054-022-03990-6
  • 发表时间:
    2022-04-30
  • 期刊:
  • 影响因子:
    15.1
  • 作者:
    Cho, Sung-Min;Wilcox, Christopher;Keller, Steven;Acton, Matthew;Rando, Hannah;Etchill, Eric;Giuliano, Katherine;Bush, Errol L.;Sair, Haris, I;Pitts, John;Kim, Bo Soo;Whitman, Glenn
  • 通讯作者:
    Whitman, Glenn
A case series evaluating the effect of esmolol therapy to treat hypoxemia in COVID-19 patients on VV-ECMO.
评估艾司洛尔治疗 VV-ECMO 治疗 COVID-19 患者低氧血症效果的病例系列。
A Computational Fluid Dynamics Study of the Extracorporeal Membrane Oxygenation-Failing Heart Circulation.
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作者回复。
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Steven Paul Keller其他文献

Steven Paul Keller的其他文献

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{{ truncateString('Steven Paul Keller', 18)}}的其他基金

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:
    9761563
  • 财政年份:
    2018
  • 资助金额:
    $ 17.06万
  • 项目类别:

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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:
    9761563
  • 财政年份:
    2018
  • 资助金额:
    $ 17.06万
  • 项目类别:
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