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Background: Endocardial ablation of atrial ganglionated plexi (GP) has been described for treatment of atrial fibrillation (AF). Our objective in this study was to develop percutaneous epicardial GP ablation in a canine model using novel energy sources and catheters., Methods: Phase 1: The efficacy of several modalities to ablate the GP was tested in an open chest canine model (n = 10). Phase 2: Percutaneous epicardial ablation of GP was done in six dogs using the most efficacious modality identified in phase 1 using two novel catheters., Results: Phase 1: Direct current (DC) in varying doses (blocking [7-12 μA], electroporation [300-500 μA], ablation [3,000-7,500 μA]), radiofrequency ablation (25-50 W), ultrasound (1.5 MHz), and alcohol (2-5 mL) injection were successful at 0/8, 4/12, 5/7, 3/8, 1/5, and 5/7 GP sites. DC (500-5,000 μA) along with alcohol irrigation was tested in phase 2. Phase 2: Percutaneous epicardial ablation of the right atrium, oblique sinus, vein of Marshall, and transverse sinus GP was successful in 5/6 dogs. One dog died of ventricular fibrillation during DC ablation at 5,000 μA. Programmed stimulation induced AF in six dogs, preablation and no atrial arrhythmia in three, flutter in one, and AF in one postablation. Heart rate, blood pressure, effective atrial refractory period, and local atrial electrogram amplitude did not change significantly postablation. Microscopic examination showed elimination of GP, and minimal injury to atrial myocardium., Conclusion: Percutaneous epicardial ablation of GP using DC and novel catheters is safe and feasible and may be used as an adjunct to pulmonary vein isolation in the treatment of AF in order to minimize additional atrial myocardial ablation., (© 2016 Wiley Periodicals, Inc.)