Effects of Vagal Nerve Stimulation on Ganglionated Plexi Nerve Activity and Ventricular Rate in Ambulatory Dogs With Persistent Atrial Fibrillation

Zhaolei Jiang, Ye Zhao, Wei Chung Tsai, Yuan Yuan, Kroekkiat Chinda, Jian Tan, Patrick Onkka, Changyu Shen, Lan Chen, Michael C. Fishbein, Shien-Fong Lin, Peng-Sheng Chen, Thomas Everett

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Abstract

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.

Original languageEnglish (US)
JournalJACC: Clinical Electrophysiology
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Vagus Nerve Stimulation
Stellate Ganglion
Atrial Fibrillation
Dogs
Confidence Intervals
Inferior Vena Cava
DNA Nucleotidylexotransferase
Staining and Labeling
Atrioventricular Node
Tyrosine 3-Monooxygenase
Canidae
Electrocardiography
Neurons

Keywords

  • atrial fibrillation
  • ganglionated plexi
  • neuromodulation
  • stellate ganglion

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Effects of Vagal Nerve Stimulation on Ganglionated Plexi Nerve Activity and Ventricular Rate in Ambulatory Dogs With Persistent Atrial Fibrillation. / Jiang, Zhaolei; Zhao, Ye; Tsai, Wei Chung; Yuan, Yuan; Chinda, Kroekkiat; Tan, Jian; Onkka, Patrick; Shen, Changyu; Chen, Lan; Fishbein, Michael C.; Lin, Shien-Fong; Chen, Peng-Sheng; Everett, Thomas.

In: JACC: Clinical Electrophysiology, 01.01.2018.

Research output: Contribution to journalArticle

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title = "Effects of Vagal Nerve Stimulation on Ganglionated Plexi Nerve Activity and Ventricular Rate in Ambulatory Dogs With Persistent Atrial Fibrillation",
abstract = "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.",
keywords = "atrial fibrillation, ganglionated plexi, neuromodulation, stellate ganglion",
author = "Zhaolei Jiang and Ye Zhao and Tsai, {Wei Chung} and Yuan Yuan and Kroekkiat Chinda and Jian Tan and Patrick Onkka and Changyu Shen and Lan Chen and Fishbein, {Michael C.} and Shien-Fong Lin and Peng-Sheng Chen and Thomas Everett",
year = "2018",
month = "1",
day = "1",
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journal = "JACC: Clinical Electrophysiology",
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T1 - Effects of Vagal Nerve Stimulation on Ganglionated Plexi Nerve Activity and Ventricular Rate in Ambulatory Dogs With Persistent Atrial Fibrillation

AU - Jiang, Zhaolei

AU - Zhao, Ye

AU - Tsai, Wei Chung

AU - Yuan, Yuan

AU - Chinda, Kroekkiat

AU - Tan, Jian

AU - Onkka, Patrick

AU - Shen, Changyu

AU - Chen, Lan

AU - Fishbein, Michael C.

AU - Lin, Shien-Fong

AU - Chen, Peng-Sheng

AU - Everett, Thomas

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

KW - atrial fibrillation

KW - ganglionated plexi

KW - neuromodulation

KW - stellate ganglion

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