There are two long term objectives of this research plan; 1) to use electrophysiological and pharmacological techniques to improve our understanding of the mechanisms responsible for atrial fibrillation and atrial flutter, and 2) to develop an improved basis for their treatment.
The specific aims of the research plan are 1) to identify the mechanism of atrial fibrillation in a newly described canine sterile pericarditis model with respect to its onset (induction), maintenance, termination (spontaneous or drug induced) and prevention (by drugs or creation of selected lesions); 2) to characterize the interrelationship between atrial flutter and atrial fibrillation in the sterile pericarditis model; and 3) to build on our previous studies of the sterile pericarditis atrial flutter model such that we better understand the components of its functionally determined reentrant circuit, especially the excitable gap, the areas of slow conduction, and the site of block of the circulating wave front during selected interventions. The central hypothesis is that atrial fibrillation in the sterile pericarditis model is generated by a single, unstable, right atrial free wall reentrant circuit (rotor) of short cycle length which drives both atria, migrates about the right atrial free wall, and cyclically disappears and reforms, whereas atrial flutter is generated by a single, stable right atrial free wall rotor. All other hypotheses relate directly or indirectly to this theme and include a series of hypotheses related to each of the specific aims. Methods to be used in these atrial arrhythmia models include the use of aseptic surgery to create the sterile pericarditis canine model; use of standard surgical techniques to expose the heart for mapping studies in the chronic sterile pericarditis model and in normal hearts; use of simultaneous multisite (multiplexing) recording techniques during the various electrophysiologic studies; the use of cardiac pacing techniques; the use of standard pharmacological techniques during the administration of selected agents; and the use of standard microelectrode techniques. The health relatedness of the project is clear, in that both atrial fibrillation and atrial flutter are well known, clinically troublesome, and poorly understood rhythms which adversely affect large numbers of patients. The proposed studies should provide important new information to assist in improved understanding and treatment of patients suffering from these rhythm disorders.
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