Atrial fibrillation (AF) has been called the arrhythmia of the 21st century since it is the most common arrhythmia whose prevalence increases as the population ages. Recent clinical studies have suggested that trains of rapid electrical discharges from the pulmonary veins induce paroxysmal (P) or episodic AF. The mechanism by which this focal activity leads to PAF is unknown. Therefore, our initial studies have concentrated on this mechanism providing for a 4 step strategy towards developing a non-invasive therapy for PAF 1) Demonstration that local autonomic nerve stimulation at the base of the pulmonary veins can cause the conversion of rapid focal firing from the pulmonary veins into PAF. 2) Demonstration that low level electrical stimuli applied to the vagosympathetic trunks can condition the cardiac ganglia so that stimuli applied to the latter will manifest a significant alteration in the threshold for induction of PAF. 3) Utilize time varying electromagnetic fields (EMFs) applied to the cervical vagosympathetic trunks in order to significantly alter the AF threshold. 4) Since magnetic components of EMFs penetrate soft tissues and bone unattenuated, our final approach will employ a large 18" Helmholtz coil by which the EMF will be applied across the chest to induce low-level electrical stimulation of intrinsic cardiac nerves. Again, the objective is to demonstrate electrical conditioning of the local cardiac autonomic nerves in order to alter baseline conditions for AF induction. In this developmental phase, all of these studies will be acutely performed in Na-pentobarbital anesthetized dogs. Our long-term objectives relate to the extension of the previously described strategies to animal models of chronic or sustained AF which if applied to the clinical arena would profoundly alter the treatment of these arrhythmias in man. This new therapeutic approach could be utilized as a non-invasive application or incorporated into an implantable device for treatment of patients with PAF.

R21AT001694

2003-07-01

2006-03-31