ELECTRICAL REMODELING IN ATRIAL FIBRILLATION

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Atrial fibrillation (AF) is the most common arrhythmia in the U.S. Growing evidence suggests that the rapid rates during AF create changes which enhances the risk of AF itself. However, the mechanisms that lead from paroxysmal to chronic AF ("electrical remodeling") are poorly understood. The proposed project attempts to determine the neural, ionic, electrophysiologic and structural mechanism of this self-perpetuating nature of (AF). The applicant plans to test the hypothesize that heterogeneous distribution of autonomic innervation and cellular connections on the atria are responsible for paroxysms of AF; and as the frequency of these paroxysms increase, chronic intracellular calcium overload occurs, resulting in permanent cell damage, leading to the downhill cascade towards chronic AF. At various stages during the transition from paroxysmal to chronic AF in a canine model we plan to 1) determine electrophysiologic measures of AF inducibility and organization; 2) map the distribution of parasympathetic and sympathetic innervation using autoradiography; 3) measure intracellular calcium using fluorescent dyes; 4) map the cellular connections (gap junctions) in the atria using immunohistochemistry; and 5) identify structural and cellular abnormalities in the atria.