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

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.

项目总结

项目成果

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: Journal of cardiac surgery
• 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: CRITICAL CARE
• 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 Computational Fluid Dynamics Study of the Extracorporeal Membrane Oxygenation-Failing Heart Circulation.

• DOI: 10.1097/mat.0000000000001221
• 发表时间: 2021-03-01
• 期刊: ASAIO journal (American Society for Artificial Internal Organs : 1992)
• 作者: Nezami FR;Khodaee F;Edelman ER;Keller SP
• 通讯作者: Keller SP

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。

• DOI: 10.1177/03913988231176839
• 发表时间: 2023
• 期刊: The International journal of artificial organs
• 作者: Kim,BoSoo;Keller,StevenP;Dodd-O,JeffreyM
• 通讯作者: Dodd-O,JeffreyM

Transcranial Doppler microemboli and acute brain injury in extracorporeal membrane oxygenation: A prospective observational study.

• DOI: 10.1016/j.xjtc.2022.07.026
• 发表时间: 2022-10
• 期刊: JTCVS TECHNIQUES
• 影响因子: 1.6
• 作者: Caturegli, Giorgio;Kapoor, Shrey;Ponomarev, Vladimir;Kim, Bo Soo;Whitman, Glenn J. R.;Ziai, Wendy;Cho, Sung-Min
• 通讯作者: Cho, Sung-Min