Atrial fibrillation (AF), the most common sustained tachyarrhythmia, has fostered intense clinical and experimental interest. The significant discomfort, morbidity and mortality as well as the increasing prevalence among the aging population have generated an on-going multidisciplinary effort to understand the underlying pathophysiology. While atrial fibrillation is a multi-symptomatic decease, the high and irregular ventricular rate is one of the major undesirable consequences. It has a direct effect on the compromised mechanical performance. Since the AV node (AVN) is the only natural barrier for the bombarding atrial impulses, its function during AF can not be overestimated. Yet very little is known about the mechanisms underlying the AVN electrophysiology during AF. In the absence of safe and effective drug therapy, one of the most frequently used non- pharmacologic treatment strategies is radiofrequency ablation (RFA). This destruction necessitates permanent pacing with an undesirable alteration of the normal sequence of ventricular depolarization. We propose to use an integrated electrophysiologic-echocardiographic approach to explore a novel nondestructive strategy for ventricular rate control during AF.
Our specific aims are:
AIM number I. To investigate how functional or anatomic modification of the atrial inputs into the AVN affects ventricular rate during AF (in-vitro studies).
AIM number 2. To investigate selective vagal stimulation of the AVN as a novel non-destructive mechanism for controlling ventricular rate during AF; also to determine how short and long term AF affects the electrical remodeling and vagal responsiveness of the AVN (in-vitro electrophysiologic and voltage-clamp studies).
AIM number 3. To evaluate and compare the effects of localized AVN vagal stimulation versus AVN ablation on ventricular rate control and ventricular mechanical performance in spontaneous AF model in-vivo (electrophysiologic and echocardiographic studies). The long-term objectives are to provide the mechanistic basis for the development of new non-destructive clinical strategies for ventricular rate control during AF that are based on the normal AVN electrophysiology and provide better mechanical heart performance. This would benefit patients with pharmacologically resistant or surgically inappropriate treatment of the disease.
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