THE ROLE OF ANATOMIC STRUCTURES IN VENTRICULAR FIBRILLATION

解剖结构在心室颤动中的作用

• 批准号: 8362803
• 负责人: Andrew D. McCulloch
• 金额: $ 3万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8362803
• 关键词: Abnormal Cell; Anatomic Models; Anatomic structures; Anatomy; Anisotropy; Arrhythmia; Automobile Driving; Biological Models; Biomedical Computing; Calcium; Cardiac; Cell model; Cells; Cicatrix; Communities; Computer software; Computing Methodologies; Coupled; Coupling; Databases; Development; Electrophysiology (science); Environment; Fibrosis; Funding; Generations; Grant; Heart; Heart failure; Heterogeneity; Infarction; Maintenance; Modeling; Myocardial; National Center for Research Resources; Normal Cell; Oryctolagus cuniculus; Pathology; Play; Principal Investigator; Property; Relative (related person); Research; Research Infrastructure; Research Personnel; Resources; Role; Source; Structure; Testing; Thick; Tissues; United States National Institutes of Health; Ventricular; Ventricular Fibrillation; cost; sudden cardiac death; tool; virtual

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 In ventricular fibrillation (VF), the leading cause of sudden cardiac death, the wave of electrical activation breaks up into a multi-wave chaotic state. Our research has focused on the question: what are the causes of this wavebreak? The traditional view was that the wave was broken up by anatomic heterogeneity, such as the curved ventricular and septal walls with their varying thicknesses, and the systematically varying anisotropy that is seen as one proceeds transmurally across the myocardial walls. The objective of our earlier research was to answer the questions: how important are anatomical heterogeneities as opposed to purely dynamical instabilities in generating and sustaining fibrillation? How do they interact? We have now shown that while the anatomic factors above can play contributory roles, the decisive role is played by the dynamical stability of conduction, which is determined by the electrophysiologic properties of the cells and tissue. We now propose to extend this research to consider the anatomic and electrophysiologic changes that are seen in heart failure. Our Specific Aims are to study arrhythmias in heart failure, and especially to tease apart the contributions to arrhythmia generation made by abnormal anatomy, on the one hand, and abnormal cell electrophysiology, on the other. To study this, we will study the normal cell in the abnormal structural heart, the abnormal cell in the normal heart and then the two pathologies, cell and tissue, together. We will use the three-dimensional ventricular anatomic models and tools developed by the NBCR investigators, and by us in conjunction with NBCR researchers, to study these questions. Specific Aim 1: To use the rabbit Virtual Heart to test the effects on cardiac wave conduction produced by adding such pathological factors as fibrosis, infarct scars, and loss of cell-to-cell electrical coupling. Specific Aim 2: To use the NBCR modeling environment to study the effects of alterations in intracellular calcium handling on the genesis and maintenance of VF. The UCSD cell systems modeling environment, coupled to the geometry models, are the ideal platforms on which to test our hypotheses that altered intracellular calcium handling is a key to the genesis of fibrillation in heart failure. Specific Aim 3: To develop anatomically realistic models of several forms of heart failure in the rabbit, and use those models together with our cell models for normal and heart failure rabbit, to test the relative contributions of altered tissue structure vs. altered cell electrophysiology, in the genesis of arrhythmias in heart failure. The proposed collaborative research will provide a driving application for the new developments in software and computational methods in Specific Aims 1 of Core [4A.2B], and the resulting new anatomic and electrophysiological meshes and models will be shared with the community via the database to be developed in Specific Aim 2. It will serve as a platform for testing and developing new bidomain models and coupled ODE solvers in Specific Aim 2.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 （一） 目标 在室颤（VF）中，心脏性猝死的主要原因， 电激活分裂成多波混沌状态。我们的研究集中在 问题是：这次海啸的原因是什么？ 传统的观点认为，波被解剖学上的不均匀性所破坏，例如： 弯曲的室壁和间隔壁及其不同的厚度，以及系统性的 变化的各向异性，其被视为穿过心肌壁进行。 我们早期研究的目的是回答以下问题： 与纯粹的动力学不稳定性相反， 持续性纤维性颤动 它们如何相互作用？ 我们现在已经表明，虽然上述解剖因素可以发挥贡献作用， 传导的动力学稳定性起着决定性的作用，这是由 细胞和组织的电生理特性。 我们现在建议扩展这项研究，考虑解剖和电生理 在心力衰竭中看到的变化。 我们的具体目标是研究心脏的心律失常 失败，特别是梳理除了心律失常产生的贡献， 一方面是异常的解剖结构，另一方面是异常的细胞电生理学。到 研究这一点，我们将研究异常结构心脏中的正常细胞， 在正常的心脏，然后两种病理，细胞和组织，在一起。 我们将使用三维心室解剖模型和工具， NBCR的研究人员，并由我们与NBCR的研究人员，研究这些 问题. 具体目的1：利用虚拟心脏测试对心电波传导的影响 通过加入诸如纤维化、梗塞疤痕和细胞间丧失等病理因素而产生 电耦合 具体目标2：使用NBCR建模环境来研究 细胞内钙处理对VF发生和维持的影响。UCSD细胞系统 与几何模型相结合的建模环境是理想的平台， 测试我们的假设，改变细胞内钙处理是一个关键的起源， 心力衰竭的纤颤 具体目标3：开发几种形式心力衰竭的解剖学现实模型， 并将这些模型与我们的正常和心力衰竭细胞模型一起使用 兔，以测试改变的组织结构与改变的细胞的相对贡献 电生理学，在心力衰竭心律失常的发生中。 拟议的合作研究将为新的 核心[4A.2B]具体目标1中的软件和计算方法的发展， 由此产生的新的解剖和电生理网格和模型将被共享 通过将在具体目标2中开发的数据库与社区联系。它将作为一个 用于测试和开发新的双主模型和耦合ODE求解器的平台， 具体目标2。