Effects of renal sympathetic denervation on the stellate ganglion and brain stem in dogs

Wei Chung Tsai, Yi Hsin Chan, Kroekkiat Chinda, Zhenhui Chen, Jheel Patel, Changyu Shen, Ye Zhao, Zhaolei Jiang, Yuan Yuan, Michael Ye, Lan Chen, Amanda A. Riley, Scott A. Persohn, Paul Territo, Thomas Everett, Shien-Fong Lin, Harry V. Vinters, Michael C. Fishbein, Peng-Sheng Chen

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Background Renal sympathetic denervation (RD) is a promising method of neuromodulation for the management of cardiac arrhythmia. Objective We tested the hypothesis that RD is antiarrhythmic in ambulatory dogs because it reduces the stellate ganglion nerve activity (SGNA) by remodeling the stellate ganglion (SG) and brain stem. Methods We implanted a radiotransmitter to record SGNA and electrocardiogram in 9 ambulatory dogs for 2 weeks, followed by a second surgery for RD and 2 months SGNA recording. Cell death was probed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Results Integrated SGNA at baseline and 1 and 2 months after RD were 14.0 ± 4.0, 9.3 ± 2.8, and 9.6 ± 2.0 μV, respectively (P = .042). The SG from RD but not normal control dogs (n = 5) showed confluent damage. An average of 41% ± 10% and 40% ± 16% of ganglion cells in the left and right SG, respectively, were TUNEL positive in RD dogs compared with 0% in controls dogs (P = .005 for both). The left and right SG from RD dogs had more tyrosine hydroxylase–negative ganglion cells than did the left SG of control dogs (P = .028 and P = .047, respectively). Extensive TUNEL-positive neurons and glial cells were also noted in the medulla, associated with strongly positive glial fibrillary acidic protein staining. The distribution was heterogeneous, with more cell death in the medial than lateral aspects of the medulla. Conclusion Bilateral RD caused significant central and peripheral sympathetic nerve remodeling and reduced SGNA in ambulatory dogs. These findings may in part explain the antiarrhythmic effects of RD.

Original languageEnglish (US)
Pages (from-to)255-262
Number of pages8
JournalHeart Rhythm
Volume14
Issue number2
DOIs
StatePublished - Feb 1 2017

Fingerprint

Stellate Ganglion
Sympathectomy
Brain Stem
Dogs
Kidney
Transferases
Ganglia
Cell Death
DNA Nucleotidylexotransferase
Glial Fibrillary Acidic Protein
Peripheral Nerves
Neuroglia
Tyrosine
Cardiac Arrhythmias
Electrocardiography
Staining and Labeling

Keywords

  • Arrhythmia
  • Nervous system
  • Neuromodulation
  • Sympathetic
  • Trans-synaptic degeneration

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Effects of renal sympathetic denervation on the stellate ganglion and brain stem in dogs. / Tsai, Wei Chung; Chan, Yi Hsin; Chinda, Kroekkiat; Chen, Zhenhui; Patel, Jheel; Shen, Changyu; Zhao, Ye; Jiang, Zhaolei; Yuan, Yuan; Ye, Michael; Chen, Lan; Riley, Amanda A.; Persohn, Scott A.; Territo, Paul; Everett, Thomas; Lin, Shien-Fong; Vinters, Harry V.; Fishbein, Michael C.; Chen, Peng-Sheng.

In: Heart Rhythm, Vol. 14, No. 2, 01.02.2017, p. 255-262.

Research output: Contribution to journalArticle

Tsai, WC, Chan, YH, Chinda, K, Chen, Z, Patel, J, Shen, C, Zhao, Y, Jiang, Z, Yuan, Y, Ye, M, Chen, L, Riley, AA, Persohn, SA, Territo, P, Everett, T, Lin, S-F, Vinters, HV, Fishbein, MC & Chen, P-S 2017, 'Effects of renal sympathetic denervation on the stellate ganglion and brain stem in dogs', Heart Rhythm, vol. 14, no. 2, pp. 255-262. https://doi.org/10.1016/j.hrthm.2016.10.003
Tsai, Wei Chung ; Chan, Yi Hsin ; Chinda, Kroekkiat ; Chen, Zhenhui ; Patel, Jheel ; Shen, Changyu ; Zhao, Ye ; Jiang, Zhaolei ; Yuan, Yuan ; Ye, Michael ; Chen, Lan ; Riley, Amanda A. ; Persohn, Scott A. ; Territo, Paul ; Everett, Thomas ; Lin, Shien-Fong ; Vinters, Harry V. ; Fishbein, Michael C. ; Chen, Peng-Sheng. / Effects of renal sympathetic denervation on the stellate ganglion and brain stem in dogs. In: Heart Rhythm. 2017 ; Vol. 14, No. 2. pp. 255-262.
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abstract = "Background Renal sympathetic denervation (RD) is a promising method of neuromodulation for the management of cardiac arrhythmia. Objective We tested the hypothesis that RD is antiarrhythmic in ambulatory dogs because it reduces the stellate ganglion nerve activity (SGNA) by remodeling the stellate ganglion (SG) and brain stem. Methods We implanted a radiotransmitter to record SGNA and electrocardiogram in 9 ambulatory dogs for 2 weeks, followed by a second surgery for RD and 2 months SGNA recording. Cell death was probed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Results Integrated SGNA at baseline and 1 and 2 months after RD were 14.0 ± 4.0, 9.3 ± 2.8, and 9.6 ± 2.0 μV, respectively (P = .042). The SG from RD but not normal control dogs (n = 5) showed confluent damage. An average of 41{\%} ± 10{\%} and 40{\%} ± 16{\%} of ganglion cells in the left and right SG, respectively, were TUNEL positive in RD dogs compared with 0{\%} in controls dogs (P = .005 for both). The left and right SG from RD dogs had more tyrosine hydroxylase–negative ganglion cells than did the left SG of control dogs (P = .028 and P = .047, respectively). Extensive TUNEL-positive neurons and glial cells were also noted in the medulla, associated with strongly positive glial fibrillary acidic protein staining. The distribution was heterogeneous, with more cell death in the medial than lateral aspects of the medulla. Conclusion Bilateral RD caused significant central and peripheral sympathetic nerve remodeling and reduced SGNA in ambulatory dogs. These findings may in part explain the antiarrhythmic effects of RD.",
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AU - Tsai, Wei Chung

AU - Chan, Yi Hsin

AU - Chinda, Kroekkiat

AU - Chen, Zhenhui

AU - Patel, Jheel

AU - Shen, Changyu

AU - Zhao, Ye

AU - Jiang, Zhaolei

AU - Yuan, Yuan

AU - Ye, Michael

AU - Chen, Lan

AU - Riley, Amanda A.

AU - Persohn, Scott A.

AU - Territo, Paul

AU - Everett, Thomas

AU - Lin, Shien-Fong

AU - Vinters, Harry V.

AU - Fishbein, Michael C.

AU - Chen, Peng-Sheng

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N2 - Background Renal sympathetic denervation (RD) is a promising method of neuromodulation for the management of cardiac arrhythmia. Objective We tested the hypothesis that RD is antiarrhythmic in ambulatory dogs because it reduces the stellate ganglion nerve activity (SGNA) by remodeling the stellate ganglion (SG) and brain stem. Methods We implanted a radiotransmitter to record SGNA and electrocardiogram in 9 ambulatory dogs for 2 weeks, followed by a second surgery for RD and 2 months SGNA recording. Cell death was probed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Results Integrated SGNA at baseline and 1 and 2 months after RD were 14.0 ± 4.0, 9.3 ± 2.8, and 9.6 ± 2.0 μV, respectively (P = .042). The SG from RD but not normal control dogs (n = 5) showed confluent damage. An average of 41% ± 10% and 40% ± 16% of ganglion cells in the left and right SG, respectively, were TUNEL positive in RD dogs compared with 0% in controls dogs (P = .005 for both). The left and right SG from RD dogs had more tyrosine hydroxylase–negative ganglion cells than did the left SG of control dogs (P = .028 and P = .047, respectively). Extensive TUNEL-positive neurons and glial cells were also noted in the medulla, associated with strongly positive glial fibrillary acidic protein staining. The distribution was heterogeneous, with more cell death in the medial than lateral aspects of the medulla. Conclusion Bilateral RD caused significant central and peripheral sympathetic nerve remodeling and reduced SGNA in ambulatory dogs. These findings may in part explain the antiarrhythmic effects of RD.

AB - Background Renal sympathetic denervation (RD) is a promising method of neuromodulation for the management of cardiac arrhythmia. Objective We tested the hypothesis that RD is antiarrhythmic in ambulatory dogs because it reduces the stellate ganglion nerve activity (SGNA) by remodeling the stellate ganglion (SG) and brain stem. Methods We implanted a radiotransmitter to record SGNA and electrocardiogram in 9 ambulatory dogs for 2 weeks, followed by a second surgery for RD and 2 months SGNA recording. Cell death was probed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Results Integrated SGNA at baseline and 1 and 2 months after RD were 14.0 ± 4.0, 9.3 ± 2.8, and 9.6 ± 2.0 μV, respectively (P = .042). The SG from RD but not normal control dogs (n = 5) showed confluent damage. An average of 41% ± 10% and 40% ± 16% of ganglion cells in the left and right SG, respectively, were TUNEL positive in RD dogs compared with 0% in controls dogs (P = .005 for both). The left and right SG from RD dogs had more tyrosine hydroxylase–negative ganglion cells than did the left SG of control dogs (P = .028 and P = .047, respectively). Extensive TUNEL-positive neurons and glial cells were also noted in the medulla, associated with strongly positive glial fibrillary acidic protein staining. The distribution was heterogeneous, with more cell death in the medial than lateral aspects of the medulla. Conclusion Bilateral RD caused significant central and peripheral sympathetic nerve remodeling and reduced SGNA in ambulatory dogs. These findings may in part explain the antiarrhythmic effects of RD.

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KW - Nervous system

KW - Neuromodulation

KW - Sympathetic

KW - Trans-synaptic degeneration

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