Original ArticleEffect of Low-level Vagus Nerve Stimulation on Cardiac Remodeling in a Rapid Atrial Pacing–induced Canine Model of Atrial FibrillationLu, Yanmei MD; Sun, Juan MD; Zhou, Xianhui MD; Zhang, Ling MD; Ma, Mei MD; Tang, Baopeng MDAuthor Information Department of Cardiology, First Affiliated Hospital, Xinjiang Medical University, Urumqi, China. Reprints: Baopeng Tang, MD, Department of Cardiology, First Affiliated Hospital, Xinjiang Medical University, Urumqi 830054, China (e-mail: [email protected]). Supported by the National Natural Science Foundation of China (NSFC81260037) and the Science Foundation of First Affiliated Hospital, Xinjiang Medical University (2012YFY23). The authors report no conflicts of interest. Y. Lu and J. Sun contributed equally to this work. Received May 20, 2015 Accepted October 15, 2015 Journal of Cardiovascular Pharmacology: March 2016 - Volume 67 - Issue 3 - p 218-224 doi: 10.1097/FJC.0000000000000338 Buy Metrics Abstract The aim of this study was to establish a rapid atrial pacing–induced canine model of atrial fibrillation in studying the effects of low-level vagus nerve stimulation (LLVNS) on atrial fibrillation 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-hour pacing group (pacing group), and a 12-hour pacing + LLVNS group (LLVNS group). All dogs underwent tests for their left and right atrial effective refractory period at various time points, after which they were killed, and samples of atrial and anterior right ganglionated plexi tissue were removed and microscopically examined. As pacing times increased, the mean effective refractory period in the pacing group became significantly shortened. The pacing group and the LLVNS group did show significant differences (P < 0.001). Three groups showed significant differences in their atrial myocardial periodic acid–Schiff–positive area staining densities. Anterior right ganglionated plexi expressions of nerve growth factor and neurturin (NRTN) in the sham group and the LLVNS group were lower than those in the pacing group (nerve growth factor in 3 groups were (36.35 ± 6.18) × 1000, (86.35 ± 5.63) × 1000, and (40.50 ± 7.24) × 1000 μm2/mm2, P < 0.001; NRTN in 3 groups were (39.28 ± 7.80) × 1000, (80.24 ± 6.56) × 1000, (40.45 ± 6.97) × 1000 μm2/mm2, 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. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.