STUDIES ON MECHANISM OF ABNORMAL CARDIAC RHYTHMS

心律异常机制的研究

• 批准号: 3346259
• 负责人: TERESA R CHAY
• 金额: $ 8.93万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-05 至 1989-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3346259
• 关键词: acetylcholine; antiarrhythmic agent; arrhythmia; calcium channel blockers; cellular pathology; computer simulation; electrophysiology; epinephrine; heart pharmacology; heart rhythm; mathematical model; quinine; tetraethylammonium compound; tetrodotoxin; verapamil

This proposal addresses five major aspects of research that will be carried out to elucidate the mechanism underlying normal/abnormal cardiac rhythms. The first part is to perform a comprehensive investigation of the phenomenon associated with phase-resetting and annihilation of single cardiac rhythm in response to external stimuli. In order to study such a phenomenon, computer simulations and bifurcation analysis will be carried out on the (previously published) cardiac electrical models. The second part is to (i) minimize the number of differential equations in these models and (ii) unified them so that one set of equations can describe electrical activity of any cardiac pacemaker cell. To obtain a simpler mathematical model we will try to find a relationship among the gating dynamic variables; to formulate a unified model we will consider the role of intracellular Ca2+ and Na+ ions and the Ca+ -buffering power of the intracellular stores, in addition to extracellular K+ compartmentation. The third part is to (i) stimulate on a computer the propagation of an impulse along a string of pacemake cardiac cells and (ii) extend it to a 2- and 3-dimensional network of excitable cells. To simulate impulse propagation on a string, we will use the mathematical model obtained in the second part; to simulate that on a 2- and 3-dimensional network, we will use a 2- variable FitzHugh-Nagumo type model. This part of research is intended to further identify the cause of cardiac arrhythmias. In the fourth part, we will examine periodic doubling and chaos that have been observed, both experimentally and theoretically, in electrical activity of the heart. To do this, we intend to construct the Poincaire first return maps and to carry out a bifurcation and power spectrum analysis using the mathematical cardiac models. From our results, we will try to identify a possible relationship between the bifurcation phenomenon and arrhythmias in the heart. In the fifth part, we will make a detailed comparison between the computer predictions and those provided by experimental sources. This will verify our simulation to be realistic and relevant to cardiophysiology.

这项建议涉及五个主要方面的研究，将进行 来阐明正常/异常心律的机制。 第一部分是全面考察 与相位重置和单粒子湮灭有关的现象 对外界刺激的反应。 为了研究这样一个 现象，计算机模拟和分岔分析将进行 在（以前出版的）心脏电模型上。 第二 （1）最小化微分方程的个数， 模型和（ii）统一它们，以便一组方程可以描述 任何心脏起搏细胞的电活动。 为了获得更简单的 数学模型，我们将试图找到门控之间的关系， 动态变量;制定统一的模型，我们将考虑的作用 细胞内Ca ~（2+）和Na ~（+）离子的浓度和细胞膜的Ca ~（+）缓冲能力 细胞内储存，除了细胞外K+区室化。 第三部分是（i）在计算机上模拟 沿着一串起搏心脏细胞脉冲，以及（ii）将其延伸到2- 和可兴奋细胞的三维网络。 为了模拟冲动 传播的字符串，我们将使用数学模型中获得的 第二部分;为了在二维和三维网络上模拟，我们将 使用2变量FitzHugh-Nagumo型模型。 这部分研究是 旨在进一步确定心律失常的原因。 在 第四部分，我们将研究周期加倍和混沌， 观察到，无论是实验和理论上，在电活动的 心脏 为了做到这一点，我们打算构建庞加莱第一回报 图，并进行分叉和功率谱分析，使用 数学心脏模型 从我们的研究结果中，我们将尝试确定一个 分叉现象与心律失常之间的可能关系 心脏 在第五部分中，我们将详细比较 计算机预测和实验来源提供的预测。 这 将验证我们的模拟是真实的和相关的心脏生理学。