MECHANOELECTRIC FEEDBACK IN CARDIAC DEFIBRILLATION

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 （一） 目标 心脏纤维性颤动是心脏紊乱的电行为，其后果是失去协调的肌肉收缩。通过及时对心脏施加强电击的电除颤长期以来一直被用作对这种心律紊乱的有效治疗，否则会致命。近年来，除颤治疗由于其改进的可及性和功能性而显著扩展。尽管该技术在挽救人类生命方面发挥着关键作用，但电击停止危及生命的心律紊乱的基本机制尚未完全了解。 机械收缩跟随心脏的电激活。然而，人们早就知道，在电和机械过程之间存在串扰，这可能在抗心律失常治疗中发挥作用。由于心脏结构和行为的复杂性，在心脏除颤机制的研究中从未考虑过机械作用。 本研究的目的是确定机械电反馈在心脏除颤过程中的作用，从而增加我们对心脏暴露于强电击终止颤动的机制的认识。该应用程序旨在继续约翰霍普金斯大学计算心脏电生理学小组和国家生物医学计算资源之间的合作。作为NBCR的一个合作项目，这项研究将促进连续性及其解剖，电气和机械模型和算法的发展，这将允许与心脏和躯干的bidomain模型更大的整合，将其开放给心脏起搏，休克和心电图的大量应用。 建议的具体目标如下： + 具体目标1：在UCSD开发的现有解剖模型的基础上，开发犬和小鼠心脏除颤的解剖学精确三维机电模型。 + 具体目标二：利用犬和小鼠心脏除颤模型，分析容量超负荷心脏除颤阈值升高的机制。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. (A) OBJECTIVES Cardiac fibrillation is disorganized electrical behavior of the heart, and its consequence is the loss of coordinated muscle contraction. Electrical defibrillation by timely application of a strong electric shock to the heart has long been used as an effective therapy for this otherwise lethal disturbance of cardiac rhythm. In recent years defibrillation therapy has dramatically expanded due to its improved accessibility and functionality. Despite the critical role that the technique plays in saving human life, the fundamental mechanisms by which electrical shocks halt life-threatening disturbances in cardiac rhythm are not completely understood. Mechanical contraction follows the electrical activation of the heart. However, it has long been known that there is a cross-talk between the electrical and mechanical processes which could play a role in anti-arrhythmia therapy. Owing to the complexities in cardiac structure and behavior, mechanical contributions have never before been considered in the investigation of cardiac defibrillation mechanisms. The objective of this research is to determine the contribution of mechanoelectrical feedback in the process of cardiac defibrillation, and thus, to increase our knowledge of the mechanisms by which the exposure of the heart to strong electric shocks terminates fibrillation. This application seeks to continue the collaboration between the Computational Cardiac Electrophysiology Group at Johns Hopkins University and the National Biomedical Computation Resource. As a collaborative project of the NBCR this research will promote extensions to the development of Continuity and its anatomic, electrical and mechanical models and algorithms that will permit greater integration with bidomain models of the heart and torso, opening it up to the large array of applications in cardiac pacing, shock and electrocardiography. The following specific aims are proposed: + Specific Aim 1: To develop an anatomically-accurate three-dimensional electromechanical model of defibrillation in dog and mouse hearts building on the existing anatomic models developed at UCSD. + Specific Aim 2: Using the dog and mouse defibrillation models to analyze the mechanisms responsible for the increase in defibrillation threshold in volume overloaded hearts.