title: Continuous low-level vagus nerve stimulation reduces stellate ganglion nerve activity and paroxysmal atrial tachyarrhythmias in ambulatory canines.
abstract: BACKGROUND
  We hypothesize that left-sided low-level vagus nerve stimulation (LL-VNS) can suppress sympathetic outflow and reduce atrial tachyarrhythmias in ambulatory dogs.
  
  
  RESULTS
  We implanted a neurostimulator in 12 dogs to stimulate the left cervical vagus nerve and a radiotransmitter for continuous recording of left stellate ganglion nerve activity, vagal nerve activities, and ECGs. Group 1 dogs (N=6) underwent 1 week of continuous LL-VNS. Group 2 dogs (N=6) underwent intermittent rapid atrial pacing followed by active or sham LL-VNS on alternate weeks. Integrated stellate ganglion nerve activity was significantly reduced during LL-VNS (7.8 mV/s; 95% confidence interval [CI] 6.94 to 8.66 versus 9.4 mV/s [95% CI, 8.5 to 10.3] at baseline; P=0.033) in group 1. The reduction was most apparent at 8 am, along with a significantly reduced heart rate (P=0.008). Left-sided low-level vagus nerve stimulation did not change vagal nerve activity. The density of tyrosine hydroxylase-positive nerves in the left stellate ganglion 1 week after cessation of LL-VNS were 99 684 μm(2)/mm(2) (95% CI, 28 850 to 170 517) in LL-VNS dogs and 186 561 μm(2)/mm(2) (95% CI, 154 956 to 218 166; P=0.008) in normal dogs. In group 2, the frequencies of paroxysmal atrial fibrillation and tachycardia during active LL-VNS were 1.4/d (95% CI, 0.5 to 5.1) and 8.0/d (95% CI, 5.3 to 12.0), respectively, significantly lower than during sham stimulation (9.2/d [95% CI, 5.3 to 13.1]; P=0.001 and 22.0/d [95% CI, 19.1 to 25.5], P<0.001, respectively).
  
  
  CONCLUSIONS
  Left-sided low-level vagus nerve stimulation suppresses stellate ganglion nerve activities and reduces the incidences of paroxysmal atrial tachyarrhythmias in ambulatory dogs. Significant neural remodeling of the left stellate ganglion is evident 1 week after cessation of continuous LL-VNS.
authors.affiliation: Krannert Institute of Cardiology, Division of Cardiology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Shen
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Shinohara
authors.forename: Hyung-Wook
authors.initials: HW
authors.lastname: Park
authors.forename: Kyle
authors.initials: K
authors.lastname: Frick
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Ice
authors.forename: Eue-Keun
authors.initials: EK
authors.lastname: Choi
authors.forename: Seongwook
authors.initials: S
authors.lastname: Han
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Maruyama
authors.forename: Rahul
authors.initials: R
authors.lastname: Sharma
authors.forename: Changyu
authors.initials: C
authors.lastname: Shen
authors.forename: Michael C
authors.initials: MC
authors.lastname: Fishbein
authors.forename: Lan S
authors.initials: LS
authors.lastname: Chen
authors.forename: John C
authors.initials: JC
authors.lastname: Lopshire
authors.forename: Douglas P
authors.initials: DP
authors.lastname: Zipes
authors.forename: Shien-Fong
authors.initials: SF
authors.lastname: Lin
authors.forename: Peng-Sheng
authors.initials: PS
authors.lastname: Chen
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004285:Dogs; D004599:Electric Stimulation Therapy / Q000379:methods*; D006321:Heart / Q000294:innervation / Q000502:physiology; D008124:Locomotion; D008297:Male; D010138:Pacemaker, Artificial; D013233:Stellate Ganglion / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000502:physiology; D013612:Tachycardia, Ectopic Atrial / Q000503:physiopathology* / Q000628:therapy*; D014630:Vagus Nerve / Q000502:physiology*