Recent experiments from our laboratory have demonstrated that chaotic dynamics are properties of excitation and impulse propagation in cardiac tissues. By focusing on these properties it might be possible to reach an understanding of the cellular mechanisms of rate-dependent conduction disturbances and, ultimately, life-threatening arrhythmias. We will investigate the cellular mechanisms of regular and irregular dynamics of rate-dependent block processes in experimental models of cardiac tissues (small pieces of rabbit atrioventricular node; unbranched and branched dog and sheep Purkinje fibers; dog and sheep Purkinje muscle junction preparations and this strips of ventricular subendocardial and epicardial muscle). We will use multiple microelectrode recordings and premature stimulation techniques to measure in these tissues recovery of excitability, restitution of action potential duration, strength/duration and strength/interval curves and effective as well as functional refractory periods under several experimental conditions. On the basis of those measurements, we will investigate the frequency-dependent patterns of activation that develop under normal conditions; and as a result of interventions that lead to various degrees of segmental depression of excitability and or/electrical uncoupling. In addition, the role of geometrical bifurcations in determining rate-dependent propagation will be studied in isolated branched Purkinje fibers. Experimental data will be compared with numerical results obtained from a """"""""difference-equation"""""""" model to determine quantitatively the conditions leading to phase-locking and /or chaotic dynamics of excitation and impulse propagation in isolated cardiac tissues. Moreover, we will apply tools derived from the theory of dynamical systems (chaos theory) to analyze the behavior of an in vitro model of circus movement reentry in the Purkinje-muscle (PM) junction. Studies will be performed in isolated canine left ventricular Purkinje- fiber-papillary muscle containing two PM junctions to determine whether sensitivity to initial conditions facilitates the development of unidirectional block and the initiation reentry. The dynamical features of stable reentry in this preparation will be studied to determine whether stable limit cycles of reentry can annihilated, or alternatively, perturbed into the basin for a strange attractor, i.e., made chaotic. The overall study should provide a quantitative basis for the understanding of normal and abnormal cardiac excitation, and should lead to an accurate description of the dynamics and cellular mechanisms of reentrant arrhythmias.
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