Atrial Fibrillation Increases Sympathetic and Parasympathetic Neurons in the Intrinsic Cardiac Nervous System

Background Chronic atrial fibrillation (AF) leads to heterogeneous autonomic nerve innervation termed neural remodeling. The quantitative changes in neural density as a function of autonomic remodeling and its association with sustained AF has not been previously determined. Method and Results Seven dogs (paced group) were chronically paced with electrodes sutured to the epicardium of left atrial appendages. Seven dogs (control animals) were not paced. All paced dogs developed sustained AF by 5 weeks of pacing. The fat pads on the atrial epicardium containing ganglionated plexuses (GP) were separated along with underlying myocardial tissue. Immunocytochemical techniques were used to identify the neurons immunoreactive to anti‐tyrosine hydroxylase (TH) and anti‐acetylcholine antibodies. After chronic AF, sympathetic and parasympathetic neurons in the atrial intrinsic cardiac ganglia increased significantly. In paced dogs, the density of sympathetic neurons was 3,022 ± 507 μm2/mm2 in the right atrial GP (vs control P < 0.01), 8,571 ± 476 μm2/mm2 in the ventral left atrial GP (vs control P < 0.0001)， 6,422 ± 464 μm2/mm2 in the dorsal atrial GP (vs control P < 0.0001) and 5,392 ± 595 μm2/mm2 in the inferior vena cava‐inferior atrial GP (vs control P