Antiarrhythmic and proarrhythmic effects of subcutaneous nerve stimulation in ambulatory dogs

Juyi Wan, Mu Chen, Yuan Yuan, Zhuo Wang, Changyu Shen, Michael C. Fishbein, Zhenhui Chen, Johnson Wong, Maria B. Grant, Thomas Everett, Peng-Sheng Chen

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: High output subcutaneous nerve stimulation (ScNS) remodels the stellate ganglia and suppresses cardiac arrhythmia. Objective: The purpose of this study was to test the hypothesis that long duration low output ScNS causes cardiac nerve sprouting and increases plasma norepinephrine concentration and the duration of paroxysmal atrial tachycardia (PAT) in ambulatory dogs. Methods: We prospectively randomized 22 dogs (11 males and 11 females) into 5 different output groups for 2 months of ScNS: 0 mA (sham) (n = 6), 0.25 mA (n = 4), 1.5 mA (n = 4), 2.5 mA (n = 4), and 3.5 mA (n = 4). Results: As compared with baseline, the changes in the durations of PAT episodes per 48 hours were significantly different among different groups (sham, −5.0 ± 9.5 seconds; 0.25 mA, 95.5 ± 71.0 seconds; 1.5 mA, −99.3 ± 39.6 seconds; 2.5 mA, −155.3 ± 87.8 seconds; and 3.5 mA, −76.3 ± 44.8 seconds; P <.001). The 3.5 mA group had a greater reduction in sinus heart rate than did the sham group (−29.8 ± 15.0 beats/min vs −14.5 ± 3.0 beats/min; P =.038). Immunohistochemical studies showed that the 0.25 mA group had a significantly increased while 2.5 mA and 3.5 mA stimulation had significantly reduced growth-associated protein 43 nerve densities in both atria and ventricles. The plasma norepinephrine concentrations in the 0.25 mA group was 5063.0 ± 4366.0 pg/mL, which was significantly higher than that in the other groups of dogs (739.3 ± 946.3; P =.009). There were no significant differences in the effects of simulation between males and females. Conclusion: In ambulatory dogs, low output ScNS causes cardiac nerve sprouting and increases plasma norepinephrine concentration and the duration of PAT episodes while high output ScNS is antiarrhythmic.

Original languageEnglish (US)
Pages (from-to)1251-1260
Number of pages10
JournalHeart Rhythm
Volume16
Issue number8
DOIs
StatePublished - Aug 1 2019

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Paroxysmal Tachycardia
Dogs
Norepinephrine
Stellate Ganglion
GAP-43 Protein
Cardiac Arrhythmias
Heart Rate

Keywords

  • Cardiac nerve sprouting
  • Excitotoxicity
  • Immunostaining
  • Nerve sprouting
  • Neuromodulation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Antiarrhythmic and proarrhythmic effects of subcutaneous nerve stimulation in ambulatory dogs. / Wan, Juyi; Chen, Mu; Yuan, Yuan; Wang, Zhuo; Shen, Changyu; Fishbein, Michael C.; Chen, Zhenhui; Wong, Johnson; Grant, Maria B.; Everett, Thomas; Chen, Peng-Sheng.

In: Heart Rhythm, Vol. 16, No. 8, 01.08.2019, p. 1251-1260.

Research output: Contribution to journalArticle

Wan, Juyi ; Chen, Mu ; Yuan, Yuan ; Wang, Zhuo ; Shen, Changyu ; Fishbein, Michael C. ; Chen, Zhenhui ; Wong, Johnson ; Grant, Maria B. ; Everett, Thomas ; Chen, Peng-Sheng. / Antiarrhythmic and proarrhythmic effects of subcutaneous nerve stimulation in ambulatory dogs. In: Heart Rhythm. 2019 ; Vol. 16, No. 8. pp. 1251-1260.
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abstract = "Background: High output subcutaneous nerve stimulation (ScNS) remodels the stellate ganglia and suppresses cardiac arrhythmia. Objective: The purpose of this study was to test the hypothesis that long duration low output ScNS causes cardiac nerve sprouting and increases plasma norepinephrine concentration and the duration of paroxysmal atrial tachycardia (PAT) in ambulatory dogs. Methods: We prospectively randomized 22 dogs (11 males and 11 females) into 5 different output groups for 2 months of ScNS: 0 mA (sham) (n = 6), 0.25 mA (n = 4), 1.5 mA (n = 4), 2.5 mA (n = 4), and 3.5 mA (n = 4). Results: As compared with baseline, the changes in the durations of PAT episodes per 48 hours were significantly different among different groups (sham, −5.0 ± 9.5 seconds; 0.25 mA, 95.5 ± 71.0 seconds; 1.5 mA, −99.3 ± 39.6 seconds; 2.5 mA, −155.3 ± 87.8 seconds; and 3.5 mA, −76.3 ± 44.8 seconds; P <.001). The 3.5 mA group had a greater reduction in sinus heart rate than did the sham group (−29.8 ± 15.0 beats/min vs −14.5 ± 3.0 beats/min; P =.038). Immunohistochemical studies showed that the 0.25 mA group had a significantly increased while 2.5 mA and 3.5 mA stimulation had significantly reduced growth-associated protein 43 nerve densities in both atria and ventricles. The plasma norepinephrine concentrations in the 0.25 mA group was 5063.0 ± 4366.0 pg/mL, which was significantly higher than that in the other groups of dogs (739.3 ± 946.3; P =.009). There were no significant differences in the effects of simulation between males and females. Conclusion: In ambulatory dogs, low output ScNS causes cardiac nerve sprouting and increases plasma norepinephrine concentration and the duration of PAT episodes while high output ScNS is antiarrhythmic.",
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AU - Chen, Mu

AU - Yuan, Yuan

AU - Wang, Zhuo

AU - Shen, Changyu

AU - Fishbein, Michael C.

AU - Chen, Zhenhui

AU - Wong, Johnson

AU - Grant, Maria B.

AU - Everett, Thomas

AU - Chen, Peng-Sheng

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N2 - Background: High output subcutaneous nerve stimulation (ScNS) remodels the stellate ganglia and suppresses cardiac arrhythmia. Objective: The purpose of this study was to test the hypothesis that long duration low output ScNS causes cardiac nerve sprouting and increases plasma norepinephrine concentration and the duration of paroxysmal atrial tachycardia (PAT) in ambulatory dogs. Methods: We prospectively randomized 22 dogs (11 males and 11 females) into 5 different output groups for 2 months of ScNS: 0 mA (sham) (n = 6), 0.25 mA (n = 4), 1.5 mA (n = 4), 2.5 mA (n = 4), and 3.5 mA (n = 4). Results: As compared with baseline, the changes in the durations of PAT episodes per 48 hours were significantly different among different groups (sham, −5.0 ± 9.5 seconds; 0.25 mA, 95.5 ± 71.0 seconds; 1.5 mA, −99.3 ± 39.6 seconds; 2.5 mA, −155.3 ± 87.8 seconds; and 3.5 mA, −76.3 ± 44.8 seconds; P <.001). The 3.5 mA group had a greater reduction in sinus heart rate than did the sham group (−29.8 ± 15.0 beats/min vs −14.5 ± 3.0 beats/min; P =.038). Immunohistochemical studies showed that the 0.25 mA group had a significantly increased while 2.5 mA and 3.5 mA stimulation had significantly reduced growth-associated protein 43 nerve densities in both atria and ventricles. The plasma norepinephrine concentrations in the 0.25 mA group was 5063.0 ± 4366.0 pg/mL, which was significantly higher than that in the other groups of dogs (739.3 ± 946.3; P =.009). There were no significant differences in the effects of simulation between males and females. Conclusion: In ambulatory dogs, low output ScNS causes cardiac nerve sprouting and increases plasma norepinephrine concentration and the duration of PAT episodes while high output ScNS is antiarrhythmic.

AB - Background: High output subcutaneous nerve stimulation (ScNS) remodels the stellate ganglia and suppresses cardiac arrhythmia. Objective: The purpose of this study was to test the hypothesis that long duration low output ScNS causes cardiac nerve sprouting and increases plasma norepinephrine concentration and the duration of paroxysmal atrial tachycardia (PAT) in ambulatory dogs. Methods: We prospectively randomized 22 dogs (11 males and 11 females) into 5 different output groups for 2 months of ScNS: 0 mA (sham) (n = 6), 0.25 mA (n = 4), 1.5 mA (n = 4), 2.5 mA (n = 4), and 3.5 mA (n = 4). Results: As compared with baseline, the changes in the durations of PAT episodes per 48 hours were significantly different among different groups (sham, −5.0 ± 9.5 seconds; 0.25 mA, 95.5 ± 71.0 seconds; 1.5 mA, −99.3 ± 39.6 seconds; 2.5 mA, −155.3 ± 87.8 seconds; and 3.5 mA, −76.3 ± 44.8 seconds; P <.001). The 3.5 mA group had a greater reduction in sinus heart rate than did the sham group (−29.8 ± 15.0 beats/min vs −14.5 ± 3.0 beats/min; P =.038). Immunohistochemical studies showed that the 0.25 mA group had a significantly increased while 2.5 mA and 3.5 mA stimulation had significantly reduced growth-associated protein 43 nerve densities in both atria and ventricles. The plasma norepinephrine concentrations in the 0.25 mA group was 5063.0 ± 4366.0 pg/mL, which was significantly higher than that in the other groups of dogs (739.3 ± 946.3; P =.009). There were no significant differences in the effects of simulation between males and females. Conclusion: In ambulatory dogs, low output ScNS causes cardiac nerve sprouting and increases plasma norepinephrine concentration and the duration of PAT episodes while high output ScNS is antiarrhythmic.

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KW - Excitotoxicity

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KW - Nerve sprouting

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