Effect of Low-level Vagus Nerve Stimulation on Cardiac Remodeling in a Rapid Atrial Pacing–induced Canine Model of Atrial Fibrillation

Abstract
This study is to establish a rapid atrial pacing (RAP)-induced canine model of atrial fibrillation (AF) in studying the effects of low-level vagus nerve stimulation (LLVNS) on AF, and the underlying mechanisms for those effects. Adult beagle dogs were randomly assigned to 3 groups: a sham operation group (sham Group), a fast left atrial appendage 12-hr pacing group (pacing Group), and a 12-hr pacing + LLVNS group (LLVNS Group). All dogs underwent tests for their left and right atrial effective refractory period (ERP) at various time points, after which they were sacrificed, and samples of atrial and anterior right ganglionated plexi (ARGP) tissue were removed and microscopically examined. As pacing times increased, the mean ERP in pacing group became significantly shortened. Pacing group and LLVNS group did show significant differences (P < 0.001). Three groups showed significant differences in their in atrial myocardial Periodic Acid-Schiff (PAS) positive area staining densities. ARGP expressions of nerve growth factor (NGF) and neurturin (NRTN) in sham group and LLVNS group were lower than those in pacing group(NGF in three groups were (36.35 ± 6.18), (86.35 ± 5.63), (40.50 ± 7.24) × 1000 μm/mm, P < 0.001;NRTN in three groups were (39.28 ± 7.80), (80.24 ± 6.56), (40.45 ± 6.97) × 1000 μm/mm, P < 0.001).Therefore, LLVNS not only reverses the effect of fast pacing- induced atrial electrical remodeling in dogs, but also exerts structural effects and stimulates remodeling of autonomic nerves.