title: Effects of renal sympathetic denervation on the stellate ganglion and brain stem in dogs.
abstract: Renal sympathetic denervation (RD) is a promising method of neuromodulation for the management of cardiac arrhythmia.
  
  
  
  We tested the hypothesis that RD is antiarrhythmic in ambulatory dogs because it reduces the stellate ganglion nerve activity (SGNA) by remodeling the stellate ganglion (SG) and brain stem.
  
  
  
  We implanted a radiotransmitter to record SGNA and electrocardiogram in 9 ambulatory dogs for 2 weeks, followed by a second surgery for RD and 2 months SGNA recording. Cell death was probed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay.
  
  
  
  Integrated SGNA at baseline and 1 and 2 months after RD were 14.0 ± 4.0, 9.3 ± 2.8, and 9.6 ± 2.0 μV, respectively (P = .042). The SG from RD but not normal control dogs (n = 5) showed confluent damage. An average of 41% ± 10% and 40% ± 16% of ganglion cells in the left and right SG, respectively, were TUNEL positive in RD dogs compared with 0% in controls dogs (P = .005 for both). The left and right SG from RD dogs had more tyrosine hydroxylase-negative ganglion cells than did the left SG of control dogs (P = .028 and P = .047, respectively). Extensive TUNEL-positive neurons and glial cells were also noted in the medulla, associated with strongly positive glial fibrillary acidic protein staining. The distribution was heterogeneous, with more cell death in the medial than lateral aspects of the medulla.
  
  
  
  Bilateral RD caused significant central and peripheral sympathetic nerve remodeling and reduced SGNA in ambulatory dogs. These findings may in part explain the antiarrhythmic effects of RD.
authors.affiliation: Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana; Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Wei-Chung
authors.initials: WC
authors.lastname: Tsai
authors.affiliation: Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana; Cardiovascular Department, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan.
authors.forename: Yi-Hsin
authors.initials: YH
authors.lastname: Chan
authors.affiliation: Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana; Department of Physiology, Faculty of Medical Science, Naresuan University, Phitsanulok, Thailand.
authors.forename: Kroekkiat
authors.initials: K
authors.lastname: Chinda
authors.affiliation: Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Zhenhui
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Jheel
authors.initials: J
authors.lastname: Patel
authors.affiliation: Department of Biostatistics, Indiana University School of Medicine and the Fairbanks School of Public Health, Indianapolis, Indiana.
authors.forename: Changyu
authors.initials: C
authors.lastname: Shen
authors.affiliation: Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana; Department of Cardiac Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana; Department of Cardiothoracic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Zhaolei
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana; Department of Cardiothoracic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Michael
authors.initials: M
authors.lastname: Ye
authors.affiliation: Department of Neurology and.
authors.forename: Lan S
authors.initials: LS
authors.lastname: Chen
authors.affiliation: Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Amanda A
authors.initials: AA
authors.lastname: Riley
authors.affiliation: Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Persohn
authors.affiliation: Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Territo
authors.affiliation: Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Everett
authors.affiliation: Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana; Institute of Biomedical Engineering, National Chiao-Tung University, Hsin-Chu, Taiwan.
authors.forename: Shien-Fong
authors.initials: SF
authors.lastname: Lin
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California.
authors.forename: Harry V
authors.initials: HV
authors.lastname: Vinters
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Fishbein
authors.affiliation: Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana. Electronic address: chenpp@iu.edu.
authors.forename: Peng-Sheng
authors.initials: PS
authors.lastname: Chen
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000601:surgery*; D001933:Brain Stem / Q000503:physiopathology*; D004285:Dogs; D006339:Heart Rate; D007668:Kidney / Q000294:innervation*; D009473:Neuronal Plasticity; D064926:Neurophysiological Monitoring / Q000379:methods; D013233:Stellate Ganglion / Q000503:physiopathology*; D013562:Sympathectomy / Q000009:adverse effects / Q000379:methods; D013564:Sympathetic Nervous System / Q000601:surgery*; D016896:Treatment Outcome
keywords: Arrhythmia; Nervous system; Neuromodulation; Sympathetic; Trans-synaptic degeneration