Background-Long-term rapid atrial pacing may result in atrial fibrillation (AF) in dogs. Whether there is histological evidence for neural remodeling is unclear. Method and Results-We performed rapid right atrial pacing in 6 dogs for 111Ϯ76 days to induce sustained AF. Tissues from 6 healthy dogs were used as controls. Immunocytochemical staining of cardiac nerves was performed using anti-growth-associated protein 43 (GAP43) and anti-tyrosine hydroxylase (TH) antibodies. In dogs with AF, the density of GAP43-positive and TH-positive nerves in the right atrium was 470Ϯ406 and 231Ϯ126 per mm 2 , respectively, which was significantly (PϽ0.001) higher than the nerve density in control tissues (25Ϯ32 and 88Ϯ40 per mm 2 , respectively). The density of GAP43-positive and TH-positive nerves in the atrial septum was 317Ϯ36 and 155Ϯ85 per mm 2 , respectively, and was significantly (PϽ0.001) higher than the nerve density in control tissues (9Ϯ13 and 30Ϯ7 per mm 2 , respectively). Similarly, the density of GAP43-positive and TH-positive nerves in the left atrium of dogs with AF was 119Ϯ61 and 91Ϯ40 per mm 2 , respectively, which was significantly (PϽ0.001) higher than the nerve density in control tissues (10Ϯ15 and 38Ϯ39 per mm 2 , respectively). Furthermore, in dogs with AF, the right atrium had a significantly higher nerve density than the left atrium. Microscopic examinations revealed an inhomogeneous distribution of cardiac nerves within each sampling site. Conclusions-Significant

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