NON LINEAR DYNAMICS OF PROPAGATION IN TWO DIMENSIONAL CARDIAC TISSUE

我们打算研究波传播的机制和动力学 通常在二维心脏组织中，以及涡旋状（螺旋形 特别是重入活动。 众所周知， 由于兴奋性、组织几何形状和细胞间耦合是必不可少的， 在这些过程中。 我们假设，除了这些因素， 波前曲率与动作电位频率依赖性 对于传播的完整描述，持续时间和波长是必要的 在二维肌肉中。 事实上，我们的初步结果表明 实验中存在频率适应现象 准备，并建议波前的曲率可能会发挥作用， 在确定传播过程中的特性的重要作用 螺旋波活动 我们将设法检验我们的预言是否正确 通过使用高分辨率光学测绘、传统的 电生理记录和计算机模拟的传播， 2-三维心肌 为此，我们将开发和使用 基于膜片钳实验和Luo & Rudy模型的一种新的离子模型 模型 尽管目前可用的离子模型适合于研究 在二维中与波前动力学相关的许多特征 细胞矩阵，他们不占许多行为，已经 证明了用于薄心肌的实验制备， 包括自我维持的螺旋波活动。 因此，我们将执行 单细胞膜片钳实验，并寻求获得参数 需要准确地再现动力学的基本离子机制， 控制动作电位持续时间和兴奋性，这决定了 心脏细胞适应极高频率的能力。 该模型将用于对以下内容进行定量和可测试的预测： 波的传播和重入激发。 此外，我们将使用 改进的视频成像系统（时间分辨率= 4毫秒）和我们的井， 建立心外膜心室肌准备，以及离子 模型，以测量传播的临界曲率及其依赖性 兴奋性和刺激频率。 这些测量结果将用于 在我们对功能核心特征的定量研究中， 螺旋波的激发间隙和波前曲率 活动，以及对其他潜在的重要预测 与波前传播的横向不稳定性有关的现象， 二维心肌 实现我们的目标应该会带来一个更好的 了解二维波传播的动力学 心肌，并提供有关的重要问题的明确答案 漩涡状折返活动的机制

We propose to investigate the mechanisms and dynamics of wave propagation in two-dimensional cardiac tissue in general, and of vortex-like (spiral wave) reentrant activity in particular. It is well known that factors such as excitability, tissue geometry and intercellular coupling are essential in these processes. We postulate that, in addition to these factors, the curvature of the wavefront and the frequency dependence of action potential duration and wavelength are necessary for a full description of propagation in two-dimensional muscle. In fact, our preliminary results demonstrate the existence of frequency adaptation phenomena in experimental preparations, and suggest that the curvature of the wavefront may play an important role in determining the characteristics of propagation during spiral wave activity. We will seek to test the validity of our conjectures by using a combination of high resolution optical mapping, conventional electrophysiologic recordings and computer simulations of propagation in - 2-dimensional cardiac muscle. For this purpose, we will develop and use a new ionic model on the ba sis of patch clamp experiments and the Luo & Rudy model. Although presently available ionic models are appropriate to study many of the features associated with wavefront dynamics in two-dimensional cell matrices, they do not account for many of the behaviors that have been demonstrated for experimental preparations of thinned cardiac muscle, including self-sustaining spiral wave activity. Thus, we will carry out patch clamp experiments in single cells and seek to derive the parameters needed to accurately reproduce essential ionic mechanisms of dynamic control of the action potential duration and excitability, which determine the ability of the cardiac cell to adapt to exceedingly high frequencies. This model will be used to make quantitative and testable predictions about wave propagation and reentrant excitation. In addition, we will use an improved video imaging system (time resolution = 4 msec) and our well- established epicardial ventricular muscle preparation, as well as an ionic model, to measure the critical curvature for propagation and its dependence on excitability and stimulation frequency. Those measurements will be used in our quantitative studies of the characteristics of the functional core, the excitable gap and the curvature of the wavefront during spiral wave activity, as well as to make predictions about other potentially important phenomena related to lateral instabilities of wavefront propagation in two-dimensional myocardium. Achieving our goals should lead to a better understanding of the dynamics of wave propagation in two dimensional cardiac muscle, and provide definite answers to important questions related to the mechanisms underlying vortex-like reentrant activity.