MECHANOELECTRIC FEEDBACK IN CARDIAC DEFIBRILLATION

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 (A)目标 心脏颤动是心脏的无序电行为，其后果是 失去协调的肌肉收缩。电除颤通过及时应用 长期以来，强烈的电击心脏一直被用作治疗这种疾病的有效方法 否则会导致致命的心律失常。近年来，除颤治疗已经 由于其改进的可访问性和功能，它大大扩展了。尽管关键的是 这项技术在拯救人类生命方面发挥的作用，其基本机制 电击停止危及生命的心律紊乱并不完全 明白了。 机械收缩伴随着心脏的电活动。然而，它已经有很长时间了 众所周知，在电气和机械过程之间存在串扰，这是 可在抗心律失常治疗中发挥作用。由于心脏结构的复杂性 和行为，机械的贡献以前从来没有被考虑过 心脏除颤机制的研究。这项研究的目的是 确定机械电反馈在心脏起搏过程中的作用 除颤，因此，增加了我们对暴露于 心脏对强烈电击的反应可终止纤颤。此应用程序旨在 继续计算心脏电生理学小组之间的合作， 约翰霍普金斯大学和国家生物医学计算资源。作为一名 NBCR的合作项目这项研究将促进该项目的推广发展 连续性及其解剖、电气和机械模型和算法将 允许与心脏和躯干的Bidomain模型更好地集成，使其向 在心脏起搏、休克和心电图学中的大量应用。 提出了以下具体目标： +具体目标1：开发一种解剖学上准确的三维 狗和小鼠心脏除颤的机电模型 加州大学圣迭戈分校开发的解剖模型。 +特定目标2：利用狗和小鼠除颤模型分析 容量过载时除颤阈值升高的机制 红心。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. (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.