Optimization of Right and Left Ventricular Coupling During Mechanical Circulatory Support

项目摘要 心源性休克是失代偿性心脏病的一种毁灭性结局， 并保持了接近50%的高死亡率。机械循环支持是随着 独特的解耦心脏供应和需求的能力，以维持终末器官灌注，同时减少心脏 工作然而，指导器械选择和滴定的方法有限。其中一个方面仍然存在， 左心室和右心室之间的相互作用及其对患者的影响的重要性尚未得到充分研究。 对设备支持的容忍度。这一点尤其重要，因为>40%的左侧支撑患者 据报告，在器械启动后发生右心衰竭，这是临床应用的主要限制。 因此，本研究采用了一种机制的方法来定义右-左心室耦合的性质， 健康和心源性休克及其对机械循环支持结果的管理。 我们将采用一种新的猪模型分级左，右心室塌陷，以确定指标的关键 分别对右心和左心适应性进行评估，以及将两者结合起来评估心室适应性的研究。 偶合器.我们将利用这一认识来评估两种形式的临床机械性双心室反应。 支持.首先，我们将测试一种经皮左心室辅助装置，该装置采用了一种机制， 持续地使左心室卸载以增加来自心脏的前向流。第二项技术将是 静脉-动脉体外膜氧合支持，通过静脉增加灌注 撤回和逆行返回到体循环;这种机制特别值得注意的是， 减轻右心和肺循环的压力。每个人提供的受控刺激 技术将允许根据心室耦合状态评估动态响应。 该项目实现了每个心室对压力反应能力的机制分析，以及 心室-心室相互作用的动态评估（而不是经典的静态指标）（包括串行 通过肺循环的相互作用，通过共享的心内结构的平行相互作用，以及 时间上的同步交互）。在这样做的时候，这项工作将提供对控制因素的深入了解， 对机械支持的响应，允许改进设备选择和滴定，并最终 改善心源性休克的破坏性后果。 我很高兴能与麻省理工学院的Elazer Edelman教授一起进行这项工作，并将这项研究与一项 严格的培训计划，这将使我成长为一个科学家，沟通者和教师。我很幸运 在一个机构和实验室，提供所有资源来完成这项新的工作，并创建一个研究 环境和培训计划，支持我走向独立的翻译研究。

PROJECT SUMMARY Cardiogenic shock, a devastating outcome of decompensated heart disease, has both increased in incidence and maintained remarkably high mortality rates near 50%. Mechanical circulatory support is emerging with the unique ability to decouple cardiac supply and demand to sustain end-organ perfusion while reducing cardiac work. However, methods to guide device selection and titration are limited. One aspect of this which remains understudied is the importance of interactions between the left and right ventricles and their power over patient tolerance to device support. This is particularly critical as >40% of patients with left-sided support have been reported to experience right heart failure after device initiation, making this a major limitation to clinical utility. Thereby, this research employs a mechanistic approach to define the nature of right-left ventricular coupling in health and cardiogenic shock and its governance of mechanical circulatory support outcomes. We will employ a novel porcine model of graded left and right ventricular collapse to determine metrics critical to right and left heart adaptability individually, and those which contextualize the two to assess ventricular coupling. We will use this understanding to assess the biventricular response to two forms of clinical mechanical support. First, we will test a percutaneous left ventricular assist device, which employs a mechanism of continuously unloading the left ventricle to increase forward flow from the heart. The second technology will be veno-arterial extracorporeal membrane oxygenation support, which increases perfusion through venous withdrawal and retrograde return into the systemic circulation; this mechanism is particularly notable for unloading and reducing stress on the right heart and pulmonary circulation. Controlled stimulus provided by each technology will allow for assessment of the dynamic response according to ventricular coupling state. This project implements mechanistic analysis of the ability of each ventricle to respond to stress, as well as dynamic assessment (rather than classic static metrics) of ventricular-ventricular interactions (including serial interactions through the pulmonary circulation, parallel interactions through shared intracardiac structures, and synchronous interactions in time). In doing so, this work will provide insight into the governing factors over the response to mechanical support, allowing for improvements in device selection and titration, and ultimately improve outcomes from the devasting consequences of cardiogenic shock. I am excited to conduct this work with MIT Professor Elazer Edelman and to couple the research with a rigorous training plan which will allow me to grow as a scientist, communicator, and teacher. I am blessed to be at an institution and laboratory which provides all resources to complete this novel work and creates a research environment and training program that supports me in advancing towards independent translational research.