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.
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