Nonlinear Dynamics and Bifurcations in Cardiac Tissue

心脏组织的非线性动力学和分叉

• 批准号: 0800793
• 负责人: Flavio Fenton
• 金额: $ 36万
• 依托单位: Cornell University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0800793&HistoricalAwards=false
• 关键词: Nonlinear; Dynamics; Bifurcations; Cardiac; Tissue

The heart utilizes electrical waves that normally spread in a coordinated manner to initiate a mechanical contraction, but in pathologic states, electrical wave propagation can be disrupted by pre-existing heterogeneous regions or by dynamic heterogeneities that develop as a consequence of rapid pacing and the nonlinear dynamics of the system. An important example of the latter that is often a precursor to life-threatening arrhythmias is electrical alternans, in which two successive paced beats elicit electrical responses (and thus mechanical responses) of different amplitudes and durations. Despite much attention, fundamental characteristics about alternans remain under-studied, and attempts to use electrical interventions to control alternans have not been successful on a global level. Our research aims to advance the understanding of cardiac alternans at the most basic level and to use this knowledge to implement improved schemes of electrical control using fundamental nonlinear dynamics principles. In particular, we will characterize the type of period-doubling bifurcation underlying electrical alternans, develop mathematical models to investigate the dynamical and biophysical mechanisms underlying alternans, and to implement and test novel control algorithms. Mathematical modeling and computer simulations in single-and multi-processor environments will be used in conjunction with experimental techniques, including microelectrodes, laser-scanning confocal microscopy, and optical mapping using fluorescence signals obtained with voltage-sensitive dyes in cardiac tissue. The proposed research will elucidate the nature of the period-doubling bifurcation to electrical alternans, quantify the roles of intracellular calcium dynamics and transmembrane voltage in the origin of alternans, and improve the understanding of global control algorithms in tissue. In the course of this project, graduate and undergraduate students will participate in this research and will benefit from an interdisciplinary environment. A key component of the project is to promote broad dissemination of information. The mathematical models and algorithms developed in this proposal will be made available free as stand alone codes and interactive Java applets via web sites. Results will be presented as well, with a special emphasis on interactive programs and animations for both scientists and the general public. Ultimately, this research may lead to improved treatments for life-threatening cardiac arrhythmias: by preventing alternans, the lethal cardiac arrhythmias that alternans can trigger also can be avoided. Furthermore, the improved understanding of electrical abnormalities and novel methods for controlling complex dynamics may translate to other related systems, including the brain and peripheral nervous system and other types of muscle.

心脏利用通常以协调方式传播的电波来启动机械收缩，但在病理状态下，电波传播可能被预先存在的异质区域或由于快速起搏和系统的非线性动力学而发展的动态异质性破坏。后者的一个重要例子是电交替，它通常是危及生命的心律失常的前兆，其中两个连续的起搏搏动引起不同幅度和持续时间的电反应（从而引起机械反应）。尽管备受关注，关于交替的基本特征仍然研究不足，并且尝试使用电干预来控制交替在全球范围内尚未成功。我们的研究旨在推进心脏交替的理解在最基本的水平，并利用这些知识来实现改进的电气控制方案，使用基本的非线性动力学原理。特别是，我们将描述倍周期分叉的类型，潜在的电交替，开发数学模型来研究交替的动力学和生物物理机制，并实施和测试新的控制算法。在单处理器和多处理器环境中的数学建模和计算机模拟将与实验技术结合使用，包括微电极，激光扫描共聚焦显微镜，以及使用心脏组织中电压敏感染料获得的荧光信号的光学映射。拟议的研究将阐明倍周期分岔电交替的性质，量化细胞内钙动力学和跨膜电压在交替起源中的作用，并提高对组织中全局控制算法的理解。在这个项目的过程中，研究生和本科生将参与这项研究，并将受益于跨学科的环境。该项目的一个关键组成部分是促进广泛传播信息。本提案中开发的数学模型和算法将作为独立代码和交互式Java小程序通过网站免费提供。结果也将被呈现，特别强调为科学家和公众提供的互动程序和动画。最终，这项研究可能会改善对危及生命的心律失常的治疗：通过预防交替发作，交替发作可能引发的致命心律失常也可以避免。此外，对电异常的更好理解和控制复杂动力学的新方法可能会转化为其他相关系统，包括大脑、周围神经系统和其他类型的肌肉。