CHAOS AND CARDIAC ARRHYTHMIAS

混乱和心律失常

• 批准号: 6564939
• 负责人: Alan J Garfinkel
• 金额: $ 23.8万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-01-01 至 2002-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6564939
• 关键词: arrhythmia; computer simulation; dogs; electrocardiography; human subject; laboratory rabbit; premature ventricular contractions; sudden cardiac death

Multiple circulating wavefronts in an excitable medium produced by computer simulations are an example of spatio-temporal chaos. Their close similarity to experimentally-recorded activation patterns during atrial or ventricular fibrillation suggest that fibrillation may also be a form of spatio-temporal chaos, and raises the possibility that recently-developed chaos control strategies can be applied to fibrillation. We have previously shown that a pacing algorithm based on chaos control theory could successfully regularize a chaotic ventricular tachycardia induced by ouabain in isolated rabbit ventricle. The major objective of this project is to determine whether a similar strategy can be developed for ventricular fibrillation. We have modified the van Capelle & Durrer computer model of propagation in a two-dimensional excitable lattice, and have shown that multiple circulating wavefronts (spiral waves) simulating fibrillation can be induced. Local site recordings show clear evidence of chaotic behavior, and exhibit the dynamic features (fixed point and stable and unstable manifolds) necessary to apply the OGY chaos control method, which we successfully applied to the chaotic ouabain-induced arrhythmia. The model closely simulates the behavior of circulating reentrant wavefronts in the in vitro canine epicardial slice preparation described in Project 2, which also shows evidence of chaos at local recording sites. Criteria for detecting spatio-temporal chaos at individual elements in the lattice (equivalent to the information that could be obtained from a local intracardiac electrogram) will be developed in the van Capelle & Durrer model, and this information used develop a perturbation strategy based on chaos control theory (analogous to pacing at a one or more sites in the lattice) to determine whether local and global chaos control can be achieved. The results of computer simulations will be directly validated experimentally using the in vitro canine epicardial slice preparation and, if successful, adapted to the in vivo fibrillating canine heart. A second objective of the project is to further understand and improve the chaos control pacing algorithm which we have previously successfully applied to ouabain-induced ventricular tachycardia in the rabbit interventricular septum, a less spatially complex chaotic cardiac arrhythmia. Using high resolution activation mapping with extracellular electrodes, the ouabain-induced arrhythmia will be mapped to evaluate its mechanism and spatial properties, and to gain insight into the mechanism by which the chaos control pacing algorithm is effective. Improvements to our current chaos control algorithm will be further developed and tested in the septal preparation. These improvements to the chaos control pacing algorithm in the ouabain-induced arrhythmia will be essential for chaos control pacing algorithms designed for fibrillation. Ultimately, the goal is to develop an intelligent pacing strategy based on chaos control theory which will either terminate fibrillation or significantly decrease the defibrillation threshold.

在可激发介质中产生的多个循环波前 计算机模拟是时空混沌的一个例子。他们的 与实验记录的激活模式非常相似 房颤或室颤提示房颤也可能是 一种时空混沌的形式，并增加了 最近发展起来的混沌控制策略可以应用于 纤颤。我们之前已经证明过，一种基于 混沌控制理论可以成功地规律化一个混沌的脑室 哇巴因诱发兔离体心动过速。少校 该项目的目标是确定类似的策略是否可以 是针对室颤而开发的。我们已经改装了这辆货车 二维传播的Capelle&Durrer计算机模型 可激发晶格，并已显示出多个循环波前 (螺旋波)可以诱导出模拟纤颤。本地站点 录音显示了混乱行为的明显证据，并展示了 动态特征(不动点、稳定和不稳定流形) 有必要应用OGY混沌控制方法，我们成功地 适用于哇巴因诱发的心律失常。模式贴近 模拟In中循环重入波阵面的行为 项目2中描述的犬体外心外膜切片制备， 还显示了当地录音地点混乱的证据。标准 检测晶格中单个元素的时空混沌 (相当于可以从本地 心内电图仪)将在van Capelle&Durrer开发 模型，并利用这些信息制定了基于 关于混沌控制理论(类似于在一个或多个地点漫步 格子)来确定局部和全局混沌控制是否可以 已实现。计算机模拟的结果将直接得到验证 犬体外心外膜片制备的实验研究 如果成功，就能适应体内纤颤的犬心。 该项目的第二个目标是进一步了解和改进 我们之前已经成功实现的混沌控制起搏算法 在哇巴因诱发兔室性心动过速中的应用 室间隔，一种空间复杂性较低的混沌心脏 心律不齐。使用细胞外高分辨率激活标测 电极，哇巴因诱发的心律失常将被标测以评估其 机制和空间属性，并深入了解机制 通过实验验证了混沌控制起搏算法的有效性。改进 对我们目前的混沌控制算法还将进一步发展和 在隔膜准备中进行了测试。这些对混乱的改善 控制起搏算法在哇巴因诱发心律失常中的应用 为颤动设计的混沌控制起搏算法的关键。 最终，我们的目标是开发基于 关于混沌控制理论，它要么终止纤颤，要么 显著降低除颤阈值。