Continuous low-level vagus nerve stimulation reduces stellate ganglion nerve activity and paroxysmal atrial tachyarrhythmias in ambulatory canines

Mark J. Shen, Tetsuji Shinohara, Hyung Wook Park, Kyle Frick, Daniel S. Ice, Eue Keun Choi, Seongwook Han, Mitsunori Maruyama, Rahul Sharma, Changyu Shen, Michael C. Fishbein, Lan Chen, John C. Lopshire, Douglas P. Zipes, Shien-Fong Lin, Peng-Sheng Chen

Research output: Contribution to journalArticle

121 Citations (Scopus)

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. Methods and 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/mm (95% CI, 28 850 to 170 517) in LL-VNS dogs and 186 561 μm/mm (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.

Original languageEnglish
Pages (from-to)2204-2212
Number of pages9
JournalCirculation
Volume123
Issue number20
DOIs
StatePublished - May 24 2011

Fingerprint

Stellate Ganglion
Vagus Nerve Stimulation
Tachycardia
Canidae
Confidence Intervals
Dogs
Implantable Neurostimulators
Vagus Nerve
Tyrosine 3-Monooxygenase
Atrial Fibrillation
Electrocardiography
Heart Rate

Keywords

  • atrial fibrillation
  • nervous system, autonomic
  • tachyarrhythmias
  • vagal nerve stimulation

ASJC Scopus subject areas

  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Cite this

Continuous low-level vagus nerve stimulation reduces stellate ganglion nerve activity and paroxysmal atrial tachyarrhythmias in ambulatory canines. / Shen, Mark J.; Shinohara, Tetsuji; Park, Hyung Wook; Frick, Kyle; Ice, Daniel S.; Choi, Eue Keun; Han, Seongwook; Maruyama, Mitsunori; Sharma, Rahul; Shen, Changyu; Fishbein, Michael C.; Chen, Lan; Lopshire, John C.; Zipes, Douglas P.; Lin, Shien-Fong; Chen, Peng-Sheng.

In: Circulation, Vol. 123, No. 20, 24.05.2011, p. 2204-2212.

Research output: Contribution to journalArticle

Shen, MJ, Shinohara, T, Park, HW, Frick, K, Ice, DS, Choi, EK, Han, S, Maruyama, M, Sharma, R, Shen, C, Fishbein, MC, Chen, L, Lopshire, JC, Zipes, DP, Lin, S-F & Chen, P-S 2011, 'Continuous low-level vagus nerve stimulation reduces stellate ganglion nerve activity and paroxysmal atrial tachyarrhythmias in ambulatory canines', Circulation, vol. 123, no. 20, pp. 2204-2212. https://doi.org/10.1161/CIRCULATIONAHA.111.018028
Shen, Mark J. ; Shinohara, Tetsuji ; Park, Hyung Wook ; Frick, Kyle ; Ice, Daniel S. ; Choi, Eue Keun ; Han, Seongwook ; Maruyama, Mitsunori ; Sharma, Rahul ; Shen, Changyu ; Fishbein, Michael C. ; Chen, Lan ; Lopshire, John C. ; Zipes, Douglas P. ; Lin, Shien-Fong ; Chen, Peng-Sheng. / Continuous low-level vagus nerve stimulation reduces stellate ganglion nerve activity and paroxysmal atrial tachyarrhythmias in ambulatory canines. In: Circulation. 2011 ; Vol. 123, No. 20. pp. 2204-2212.
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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. Methods and 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/mm (95{\%} CI, 28 850 to 170 517) in LL-VNS dogs and 186 561 μm/mm (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.",
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T1 - Continuous low-level vagus nerve stimulation reduces stellate ganglion nerve activity and paroxysmal atrial tachyarrhythmias in ambulatory canines

AU - Shen, Mark J.

AU - Shinohara, Tetsuji

AU - Park, Hyung Wook

AU - Frick, Kyle

AU - Ice, Daniel S.

AU - Choi, Eue Keun

AU - Han, Seongwook

AU - Maruyama, Mitsunori

AU - Sharma, Rahul

AU - Shen, Changyu

AU - Fishbein, Michael C.

AU - Chen, Lan

AU - Lopshire, John C.

AU - Zipes, Douglas P.

AU - Lin, Shien-Fong

AU - Chen, Peng-Sheng

PY - 2011/5/24

Y1 - 2011/5/24

N2 - Background-: We hypothesize that left-sided low-level vagus nerve stimulation (LL-VNS) can suppress sympathetic outflow and reduce atrial tachyarrhythmias in ambulatory dogs. Methods and 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/mm (95% CI, 28 850 to 170 517) in LL-VNS dogs and 186 561 μm/mm (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.

AB - Background-: We hypothesize that left-sided low-level vagus nerve stimulation (LL-VNS) can suppress sympathetic outflow and reduce atrial tachyarrhythmias in ambulatory dogs. Methods and 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/mm (95% CI, 28 850 to 170 517) in LL-VNS dogs and 186 561 μm/mm (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.

KW - atrial fibrillation

KW - nervous system, autonomic

KW - tachyarrhythmias

KW - vagal nerve stimulation

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