This is an application to produce a quantitative analysis of the dynamics and mechanisms of acute sustained atrial fibrillation (AF) in Langendorff-perfused sheep hearts. A major goal is to determine the role played by discrete atrial structures in the dynamics of wave propagation and mechanisms of AF. The general hypothesis is that the intricate 3D musculature of the atria plays a major role in the maintenance of AF. Specifically, it is proposed that acute AF induced by burst pacing depends on 1) uninterrupted periodic reentrant activity within discrete areas of the atria, with the shortest reentrant circuits acting a dominant frequency source that drives the atria and maintains sustained AF activity; and, 2) the high frequency of wave fronts emanating from the source areas interact with anatomical and/or functional obstacles, which produces fragmentation of the wave front and wavelet formation. Preliminary experimental results using Fast Fourier Transforms (FFTs) show that the dominant frequency peak of overall atrial electrical events correlates with local areas of periodic activity (i.e., uninterrupted patterns of reentry within the left atrium). Preliminary results also show that areas with aperiodic activity (multiple variable wavefronts) have relatively low local AF activation frequencies versus the periodic areas that have higher local activation frequencies, and these areas are separated by gross anatomical structures between the two atria, such as the atrial septum and Bachmann's bundle. There are three specific aims. 1) To combine epicardial optical mapping with frequency analysis and statistical techniques to identify discrete areas of spatiotemporal periodicity, which are identified as areas that have similar recurrent AF activation intervals with similar activation sequences. Once these areas have been identified, their contribution to the frequency content of the global atrial electrogram will be determined. 2) To use the optical mapping system and electrical signals recorded with 16 electrodes as a combined approach for spectral analysis of the electrical activity of a large number of atrial areas during AF. The optical signals, along with the bipolar electrical recordings at multiple sites, will be used as a systematic approach to localize the sources that produce the dominant frequencies in the FFTs. 3) To provide a quantitative understanding of the mechanisms of wavelet formation and of the complex patterns of activation spread that characterize AF. Mechanisms will be defined in the context of nonlinear dynamics by using the concepts of the general theory of wave propagation in excitable media, and newly developed analytical tools will be used to account for the fragmentation of wave fronts by phase singularity points that produce wavelets.
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