Intermittent left cervical vagal nerve stimulation damages the stellate ganglia and reduces the ventricular rate during sustained atrial fibrillation in ambulatory dogs

Kroekkiat Chinda, Wei Chung Tsai, Yi Hsin Chan, Andrew Y T Lin, Jheel Patel, Ye Zhao, Alex Y. Tan, Mark J. Shen, Hongbo Lin, Changyu Shen, Nipon Chattipakorn, Michael Rubart-von der Lohe, Lan Chen, Michael C. Fishbein, Shien-Fong Lin, Zhenhui Chen, Peng-Sheng Chen

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Background The effects of intermittent open-loop vagal nerve stimulation (VNS) on the ventricular rate (VR) during atrial fibrillation (AF) remain unclear. Objective The purpose of this study was to test the hypothesis that VNS damages the stellate ganglion (SG) and improves VR control during persistent AF. Methods We performed left cervical VNS in ambulatory dogs while recording the left SG nerve activity (SGNA) and vagal nerve activity. Tyrosine hydroxylase (TH) staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were used to assess neuronal cell death in the SG. Results We induced persistent AF by atrial pacing in 6 dogs, followed by intermittent VNS with short ON-time (14 seconds) and long OFF-time (66 seconds). The integrated SGNA and VR during AF were 4.84 mV·s (95% confidence interval [CI] 3.08-6.60 mV·s) and 142 beats/min (95% CI 116-168 beats/min), respectively. During AF, VNS reduced the integrated SGNA and VR, respectively, to 3.74 mV·s (95% CI 2.27-5.20 mV·s; P =.021) and 115 beats/min (95% CI 96-134 beats/min; P =.016) during 66-second OFF-time and to 4.07 mV·s (95% CI 2.42-5.72 mV·s; P =.037) and 114 beats/min (95% CI 83-146 beats/min; P =.039) during 3-minute OFF-time. VNS increased the frequencies of prolonged (>3 seconds) pauses during AF. TH staining showed large confluent areas of damage in the left SG, characterized by pyknotic nuclei, reduced TH staining, increased percentage of TH-negative ganglion cells, and positive TUNEL staining. Occasional TUNEL-positive ganglion cells were also observed in the right SG. Conclusion VNS damaged the SG, leading to reduced SGNA and better rate control during persistent AF.

Original languageEnglish (US)
Pages (from-to)771-780
Number of pages10
JournalHeart Rhythm
Volume13
Issue number3
DOIs
StatePublished - Mar 1 2016

Fingerprint

Stellate Ganglion
Vagus Nerve Stimulation
Atrial Fibrillation
Dogs
Tyrosine 3-Monooxygenase
Confidence Intervals
Staining and Labeling
Transferases
Ganglia
DNA Nucleotidylexotransferase
Cell Death

Keywords

  • Atrial fibrillation
  • Excitotoxicity
  • Vagal nerve stimulation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Intermittent left cervical vagal nerve stimulation damages the stellate ganglia and reduces the ventricular rate during sustained atrial fibrillation in ambulatory dogs. / Chinda, Kroekkiat; Tsai, Wei Chung; Chan, Yi Hsin; Lin, Andrew Y T; Patel, Jheel; Zhao, Ye; Tan, Alex Y.; Shen, Mark J.; Lin, Hongbo; Shen, Changyu; Chattipakorn, Nipon; Rubart-von der Lohe, Michael; Chen, Lan; Fishbein, Michael C.; Lin, Shien-Fong; Chen, Zhenhui; Chen, Peng-Sheng.

In: Heart Rhythm, Vol. 13, No. 3, 01.03.2016, p. 771-780.

Research output: Contribution to journalArticle

Chinda, Kroekkiat ; Tsai, Wei Chung ; Chan, Yi Hsin ; Lin, Andrew Y T ; Patel, Jheel ; Zhao, Ye ; Tan, Alex Y. ; Shen, Mark J. ; Lin, Hongbo ; Shen, Changyu ; Chattipakorn, Nipon ; Rubart-von der Lohe, Michael ; Chen, Lan ; Fishbein, Michael C. ; Lin, Shien-Fong ; Chen, Zhenhui ; Chen, Peng-Sheng. / Intermittent left cervical vagal nerve stimulation damages the stellate ganglia and reduces the ventricular rate during sustained atrial fibrillation in ambulatory dogs. In: Heart Rhythm. 2016 ; Vol. 13, No. 3. pp. 771-780.
@article{b764cf7af7014438bdb3c3ee70944460,
title = "Intermittent left cervical vagal nerve stimulation damages the stellate ganglia and reduces the ventricular rate during sustained atrial fibrillation in ambulatory dogs",
abstract = "Background The effects of intermittent open-loop vagal nerve stimulation (VNS) on the ventricular rate (VR) during atrial fibrillation (AF) remain unclear. Objective The purpose of this study was to test the hypothesis that VNS damages the stellate ganglion (SG) and improves VR control during persistent AF. Methods We performed left cervical VNS in ambulatory dogs while recording the left SG nerve activity (SGNA) and vagal nerve activity. Tyrosine hydroxylase (TH) staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were used to assess neuronal cell death in the SG. Results We induced persistent AF by atrial pacing in 6 dogs, followed by intermittent VNS with short ON-time (14 seconds) and long OFF-time (66 seconds). The integrated SGNA and VR during AF were 4.84 mV·s (95{\%} confidence interval [CI] 3.08-6.60 mV·s) and 142 beats/min (95{\%} CI 116-168 beats/min), respectively. During AF, VNS reduced the integrated SGNA and VR, respectively, to 3.74 mV·s (95{\%} CI 2.27-5.20 mV·s; P =.021) and 115 beats/min (95{\%} CI 96-134 beats/min; P =.016) during 66-second OFF-time and to 4.07 mV·s (95{\%} CI 2.42-5.72 mV·s; P =.037) and 114 beats/min (95{\%} CI 83-146 beats/min; P =.039) during 3-minute OFF-time. VNS increased the frequencies of prolonged (>3 seconds) pauses during AF. TH staining showed large confluent areas of damage in the left SG, characterized by pyknotic nuclei, reduced TH staining, increased percentage of TH-negative ganglion cells, and positive TUNEL staining. Occasional TUNEL-positive ganglion cells were also observed in the right SG. Conclusion VNS damaged the SG, leading to reduced SGNA and better rate control during persistent AF.",
keywords = "Atrial fibrillation, Excitotoxicity, Vagal nerve stimulation",
author = "Kroekkiat Chinda and Tsai, {Wei Chung} and Chan, {Yi Hsin} and Lin, {Andrew Y T} and Jheel Patel and Ye Zhao and Tan, {Alex Y.} and Shen, {Mark J.} and Hongbo Lin and Changyu Shen and Nipon Chattipakorn and {Rubart-von der Lohe}, Michael and Lan Chen and Fishbein, {Michael C.} and Shien-Fong Lin and Zhenhui Chen and Peng-Sheng Chen",
year = "2016",
month = "3",
day = "1",
doi = "10.1016/j.hrthm.2015.11.031",
language = "English (US)",
volume = "13",
pages = "771--780",
journal = "Heart Rhythm",
issn = "1547-5271",
publisher = "Elsevier",
number = "3",

}

TY - JOUR

T1 - Intermittent left cervical vagal nerve stimulation damages the stellate ganglia and reduces the ventricular rate during sustained atrial fibrillation in ambulatory dogs

AU - Chinda, Kroekkiat

AU - Tsai, Wei Chung

AU - Chan, Yi Hsin

AU - Lin, Andrew Y T

AU - Patel, Jheel

AU - Zhao, Ye

AU - Tan, Alex Y.

AU - Shen, Mark J.

AU - Lin, Hongbo

AU - Shen, Changyu

AU - Chattipakorn, Nipon

AU - Rubart-von der Lohe, Michael

AU - Chen, Lan

AU - Fishbein, Michael C.

AU - Lin, Shien-Fong

AU - Chen, Zhenhui

AU - Chen, Peng-Sheng

PY - 2016/3/1

Y1 - 2016/3/1

N2 - Background The effects of intermittent open-loop vagal nerve stimulation (VNS) on the ventricular rate (VR) during atrial fibrillation (AF) remain unclear. Objective The purpose of this study was to test the hypothesis that VNS damages the stellate ganglion (SG) and improves VR control during persistent AF. Methods We performed left cervical VNS in ambulatory dogs while recording the left SG nerve activity (SGNA) and vagal nerve activity. Tyrosine hydroxylase (TH) staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were used to assess neuronal cell death in the SG. Results We induced persistent AF by atrial pacing in 6 dogs, followed by intermittent VNS with short ON-time (14 seconds) and long OFF-time (66 seconds). The integrated SGNA and VR during AF were 4.84 mV·s (95% confidence interval [CI] 3.08-6.60 mV·s) and 142 beats/min (95% CI 116-168 beats/min), respectively. During AF, VNS reduced the integrated SGNA and VR, respectively, to 3.74 mV·s (95% CI 2.27-5.20 mV·s; P =.021) and 115 beats/min (95% CI 96-134 beats/min; P =.016) during 66-second OFF-time and to 4.07 mV·s (95% CI 2.42-5.72 mV·s; P =.037) and 114 beats/min (95% CI 83-146 beats/min; P =.039) during 3-minute OFF-time. VNS increased the frequencies of prolonged (>3 seconds) pauses during AF. TH staining showed large confluent areas of damage in the left SG, characterized by pyknotic nuclei, reduced TH staining, increased percentage of TH-negative ganglion cells, and positive TUNEL staining. Occasional TUNEL-positive ganglion cells were also observed in the right SG. Conclusion VNS damaged the SG, leading to reduced SGNA and better rate control during persistent AF.

AB - Background The effects of intermittent open-loop vagal nerve stimulation (VNS) on the ventricular rate (VR) during atrial fibrillation (AF) remain unclear. Objective The purpose of this study was to test the hypothesis that VNS damages the stellate ganglion (SG) and improves VR control during persistent AF. Methods We performed left cervical VNS in ambulatory dogs while recording the left SG nerve activity (SGNA) and vagal nerve activity. Tyrosine hydroxylase (TH) staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were used to assess neuronal cell death in the SG. Results We induced persistent AF by atrial pacing in 6 dogs, followed by intermittent VNS with short ON-time (14 seconds) and long OFF-time (66 seconds). The integrated SGNA and VR during AF were 4.84 mV·s (95% confidence interval [CI] 3.08-6.60 mV·s) and 142 beats/min (95% CI 116-168 beats/min), respectively. During AF, VNS reduced the integrated SGNA and VR, respectively, to 3.74 mV·s (95% CI 2.27-5.20 mV·s; P =.021) and 115 beats/min (95% CI 96-134 beats/min; P =.016) during 66-second OFF-time and to 4.07 mV·s (95% CI 2.42-5.72 mV·s; P =.037) and 114 beats/min (95% CI 83-146 beats/min; P =.039) during 3-minute OFF-time. VNS increased the frequencies of prolonged (>3 seconds) pauses during AF. TH staining showed large confluent areas of damage in the left SG, characterized by pyknotic nuclei, reduced TH staining, increased percentage of TH-negative ganglion cells, and positive TUNEL staining. Occasional TUNEL-positive ganglion cells were also observed in the right SG. Conclusion VNS damaged the SG, leading to reduced SGNA and better rate control during persistent AF.

KW - Atrial fibrillation

KW - Excitotoxicity

KW - Vagal nerve stimulation

UR - http://www.scopus.com/inward/record.url?scp=84958890232&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84958890232&partnerID=8YFLogxK

U2 - 10.1016/j.hrthm.2015.11.031

DO - 10.1016/j.hrthm.2015.11.031

M3 - Article

VL - 13

SP - 771

EP - 780

JO - Heart Rhythm

JF - Heart Rhythm

SN - 1547-5271

IS - 3

ER -