Although atrial fibrillation is an extremely prevalent arrhythmia with significant concomitant morbidity, the treatment of it currently is limited as is knowledge of its mechanism. Specifically, it is not known how reentrant wave fronts are generated and terminated during atrial fibrillation. Few in vitro and animal studies exist and even less is known about human atrial fibrillation. Furthermore, the existing theoretical models of atrial fibrillation are inadequate to explain the observed behaviors of these reentrant wave fronts. The applicant plans to study the mechanisms of reentry in atrial fibrillation using a high density, computerized mapping system in humans and in an animal model. The specific aims include 1) mapping of human atrial fibrillation in the operating room, 2) mechanism of atrial vulnerability to single premature stimuli in dogs, 3) atrial protective zone in dogs, 4) creating a canine model of chronic atrial fibrillation, 5) effects of antiarrhythmic drugs on reentry in atrial fibrillation, and 6) radiofrequency ablation of chronic atrial fibrillation in dogs. The broad long term objectives of these studies are to understand the mechanisms by which reentrant wave fronts are generated and terminated, and how one can control them with external perturbation. The findings will likely provide insights into designing future therapeutic modality for atrial fibrillation.