Ventricular tachycardia (VT) and ventricular fibrillation (VF) may result from vortex-like reentrant excitation of the myocardium. Our general hypothesis is that, in the structurally normal heart, these arrhythmias are the result of 3-dimensional (3-D) electrical scroll waves activating the heart muscle at very high frequencies. To test this hypothesis, we will combine the use of high-resolution optical mapping, electrocardiography and vectorcardiography, together with mathematical modelling of the isolated rabbit hart. Our studies will be directed toward determining whether sustained monomorphic reentrant VT is the result of a stationary (anchored) scroll wave; whether polymorphic VT is the result of a nonstationary scroll wave; and whether VF is the result of the coexistence of a small n umber of nonstationary scroll waves. To this aim we will first characterize the electrical activity of the Langendorff-perfused heart in response to changes in specific parameters, such as temperature, action potential duration (APD), conduction velocity (CV) and basic cycle length, which may determine our ability to initiate vortex-like reentrant excitation. We will then study the role of spatial nonuniformities (i.e., gradients) in APD and CV in the genesis and subsequent evolution of vortex-like reentry, as well as in determining the type of arrhythmias (e.g., monomorphic or polymorphic VT; VF) that may occur. in addition, we will quantify the dynamics of spiral waves on the entire epicardial surface of the ventricles to establish whether such dynamics are consistent with 3-D scroll waves in excitable media. Further, we will use analytical tools to study the degree of spatial and temporal organization of wave propagation on the epicardial surface during t=sinus rhythm, ventricular pacing, VT and VF. To investigate three-dimensional aspects of wave propagation in these studies we will record three orthogonal ECG leads for the construction of 3-D vectorcardiographic loops while simultaneously obtaining optical maps of the entire ventricular surface. Finally, we will use a 3-D """"""""cube"""""""" model, as well as a model of the intact right and left ventricles of the heart based on FitzHugh-Nagumo kinetics, and on realistic Magnetic Resonance Imaging data of heart geometry, as guides to study the nonlinear dynamics of scroll waves in our preparations. Particular attention will be given to the epicardial surface manifestation, ECG and 3-D vectorcardiographic loop pattern of reentrant activity generated by one or more scroll waves which may be established at the right or left ventricles, or even at the ventricular septum. Attention will also be given to the shape and location of the scroll filament in relation to the myocardial wall. Overall, the studies proposed here promise answers that relate importantly to the understanding of wave propagation in the heart. Moreover, achieving our goals may help to improve our ability to identify the mechanisms of life-threatening tachyarrhythmias in the diseased heart.
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