Atrial fibrillation increases sympathetic and parasympathetic neurons in the intrinsic cardiac nervous system.

Abstract

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. 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 μm(2) /mm(2) in the right atrial GP (vs control P < 0.01), 8,571 ± 476 μm(2) /mm(2) in the ventral left atrial GP (vs control P < 0.0001)， 6,422 ± 464 μm(2) /mm(2) in the dorsal atrial GP (vs control P < 0.0001) and 5,392 ± 595 μm(2) /mm(2) in the inferior vena cava-inferior atrial GP (vs control P <0.0001), respectively. The density of parasympathetic neurons was 4,396 ± 877 μm(2) /mm(2) in the right atrial GP, 7,769 ± 465 μm(2) /mm(2) in the ventral left atrial GP， 7,016.47 ± 687 μm(2) /mm(2) in the dorsal atrial GP and 5,485 ± 554 μm(2) /mm(2) in the inferior vena cava-inferior atrial GP, respectively, which was higher than control cohorts in corresponding GP (P < 0.05). This study provides evidence for the remodeling in atrial intrinsic cardiac ganglia in the dogs with pacing induced AF. A significant increase of sympathetic and parasympathetic neurons was present in atrial intrinsic cardiac ganglia.