Author + information
- Received October 24, 2017
- Revision received May 3, 2018
- Accepted May 4, 2018
- Published online June 27, 2018.
- Zhaolei Jiang, MDa,b,
- Ye Zhao, MDa,c,
- Wei-Chung Tsai, MDa,d,
- Yuan Yuan, MDa,b,
- Kroekkiat Chinda, DVM, PhDa,e,
- Jian Tan, MSa,
- Patrick Onkka, MDa,
- Changyu Shen, PhDf,
- Lan S. Chen, MDg,
- Michael C. Fishbein, MDh,
- Shien-Fong Lin, PhDi,
- Peng-Sheng Chen, MDa and
- Thomas H. Everett IV, PhDa,∗ ()
- aKrannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana
- bDepartment of Cardiothoracic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
- cDepartment of Cardiac Surgery, the First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China
- dDivision of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- eDepartment of Physiology, Faculty of Medical Science, Naresuan University, Phitsanulok, Thailand
- fRichard and Susan Smith Center for Outcomes Research in Cardiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
- gDepartment of Neurology, Indiana University School of Medicine, Indianapolis, Indiana
- hDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California
- iInstitute of Biomedical Engineering, National Chiao-Tung University, Hsin-Chu, Taiwan
- ↵∗Address for correspondence:
Dr. Thomas H. Everett, IV, Krannert Institute of Cardiology, Department of Medicine, Indiana University School of Medicine, 1800 North Capitol Avenue, E400E, Indianapolis, Indiana 46202.
Objectives This study was designed to test the hypothesis that low-level vagal nerve stimulation (VNS) reduces the ventricular rate (VR) during atrial fibrillation (AF) through the activation of the inferior vena cava (IVC)–inferior atrial ganglionated plexus nerve activity (IAGPNA).
Background Increased IVC-IAGPNA can suppress atrioventricular node conduction and slow VR in canine models of AF.
Methods Persistent AF was induced in 6 dogs and the IVC-IAGPNA, right vagal nerve activity, left vagal nerve activity, and an electrocardiogram were recorded. After persistent AF was documented, VNS was programed to 14 s “on” and 1.1 min “off.” After 1 week, the VNS was reprogramed to 3 min off and stimulation continued for another week. Neural remodeling of the stellate ganglion (SG) was assessed with tyrosine hydroxylase staining and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling staining.
Results Average IVC-IAGPNA was increased during both VNS 1.1 min off (8.20 ± 2.25 μV [95% confidence interval (CI): 6.33 to 9.53 μV], p = 0.002) and 3 min off (7.96 ± 2.03 μV [95% CI: 6.30 to 9.27 μV], p = 0.001) versus baseline (7.14 ± 2.20 μV [95% CI: 5.35 to 8.52 μV]). VR was reduced during both VNS 1.1 min off (123.29 ± 6.29 beats/min [95% CI: 116.69 to 129.89 beats/min], p = 0.001) and 3 min off (120.01 ± 4.93 beats/min [95% CI: 114.84 to 125.18 beats/min], p = 0.001) compared to baseline (142.04 ± 7.93 bpm [95% CI: 133.72 to 150.37]). Abnormal regions were observed in the left SG, but not in the right SG. Terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling–positive neurons were found in 22.2 ± 17.2% [95% CI: 0.9% to 43.5%] of left SG cells and 12.8 ± 8.4% [95% CI: 2.4% to 23.2%] of right SG cells.
Conclusions Chronic low-level VNS increases IVC-IAGPNA and damages bilateral stellate ganglia. Both mechanisms could contribute to the underlying mechanism of VR control during AF.
This study was supported in part by NIH grants R42DA043391 (to Dr. Everett), P01 HL78931, R56 HL71140, R01 HL71140, U18 TR002208-01, and R01 HL139829 (Dr. Chen), a Charles Fisch Cardiovascular Research Award endowed by Dr. Suzanne B. Knoebel of the Krannert Institute of Cardiology (Dr. Everett), a Medtronic-Zipes Endowment and the Indiana University Health-Indiana University School of Medicine Strategic Research Initiative (Dr. P.-S. Chen). Medtronic and St. Jude Medical, Inc., donated research equipment to Dr. P.-S. Chen’s research laboratory. Drs. Lin and Everett have equity interest in Arrythmotech, LLC. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
All authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Clinical Electrophysiology author instructions page.
- Received October 24, 2017.
- Revision received May 3, 2018.
- Accepted May 4, 2018.
- 2018 American College of Cardiology Foundation
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