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A potential link between left stellate ganglion and renal sympathetic nerve: An important mechanism for cardiac arrhythmias?
International Journal of Cardiology 179 (2015) 123–124
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
A potential link between left stellate ganglion and renal sympathetic nerve: An important mechanism for cardiac arrhythmias? Bing Huang, Lilei Yu, Hong Jiang ⁎ Department of Cardiology, Renmin Hospital of Wuhan University, Cardiovascular Research Institute of Wuhan University, Wuhan, China
a r t i c l e
i n f o
Article history: Received 25 August 2014 Received in revised form 9 October 2014 Accepted 18 October 2014 Available online 22 October 2014 Keywords: Cardiac arrhythmias Autonomic nervous system Left stellate ganglion Renal sympathetic nerve
Atrial fibrillation is the most common arrhythmia in clinical practice, and ventricular arrhythmias represent the major mechanism of sudden cardiac death which is the leading cause of death in United States. It is now well established that the autonomic nervous system has an important role in the genesis and maintenance of these cardiac arrhythmias [1]. Therefore, modulating autonomic activity has been proposed as a method to potentially suppress cardiac arrhythmias. Increased nerve activity of left stellate ganglion (LSG) has been shown to contribute to the generation of cardiac arrhythmias. In a canine model of atrial pacing-induced atrial fibrillation, Tan et al. found that simultaneous sympathovagal discharges (recording from LSG and left vagal nerve) were common triggers of paroxysmal atrial tachyarrhythmias, which could be eliminated by cryoablation of extrinsic sympathovagal nerves [2]. Chen and colleagues [3,4] found that infusion of nerve growth factor or applying electrical stimulation to the LSG following myocardial infarction increased nerve density and ventricular arrhythmias. Direct nerve activity recording from the LSG in a canine model of sudden cardiac death showed that most ventricular tachycardia (86.3%) and sudden cardiac death were triggered by increased LSG nerve activity [5]. Interventions that decrease nerve activity of LSG are often antiarrhythmic. For example, inhibition of LSG nerve activity by chronic low-level vagus nerve stimulation significantly reduces the frequencies of paroxysmal atrial fibrillation (1.4/d versus 9.2/d in sham ⁎ Corresponding author at: Department of Cardiology, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuchang District, Wuhan City, Hubei Province 430060, China. E-mail address: [email protected] (H. Jiang).
http://dx.doi.org/10.1016/j.ijcard.2014.10.046 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
stimulation group) and atrial tachycardia (8.0/d versus 22.0/d in sham stimulation group) in ambulatory dogs [6]. Clinical evidence has shown that left cardiac sympathetic denervation, e.g. LSG resection, is able to prevent recurrence of malignant ventricular arrhythmias in high-risk patients [7]. These observations suggest that LSG plays an important role in the pathogenesis of cardiac arrhythmias. Renal sympathetic nerve (RSN), which has been identified as an important mediator of systemic sympathetic tone, may also be involved in the pathogenesis of cardiac arrhythmias. Clinical studies suggest that patients with chronic kidney disease, which is always accompanied by RSN activation, are associated with higher prevalence of atrial fibrillation [8] and sudden cardiac death [9] compared to those without chronic kidney disease. In recent years, RSN has become an interesting intervention target for the treatment of many diseases associated with chronic sympathetic activation [10], including cardiac arrhythmias [11–13]. Linz et al. showed that RSN denervation was able to prevent obstructive sleep apnea-associated atrial fibrillation [14] and acute ischemia-induced ventricular arrhythmias [15]. In a canine model of pacing-induced heart failure, Zhao and colleagues found that RSN denervation could suppress the atrial substrate remodeling and the atrial fibrillation vulnerability [16] as well as the ventricular substrate remodeling and the ventricular tachyarrhythmia vulnerability [17]. In a small human study [11], 9 of the 13 patients (69%) treated with circumferential pulmonary vein isolation (PVI) with RSN denervation had no longer atrial fibrillation recurrences at the 12-month post-ablation follow-up versus 4 of the 14 patients (29%) in the PVI-only group, indicating that RSN denervation significantly reduced atrial fibrillation recurrences when combined with PVI in patients with resistant hypertension. In addition, several case reports [12,13] have recently suggested that RSN denervation is an effective and safe therapy for the treatment of ventricular electrical storm. These results indicate that RSN may be a potential therapeutic target for cardiac arrhythmias. Recent studies showed that there is an association between LSG and RSN. Hou et al. [18] showed that RSN denervation could reduce atrial fibrillation inducibility and reverse atrial electrophysiological changes in a canine model of hyper-sympathetic activity induced by 3-hour LSG stimulation plus rapid atrial pacing. Tsai et al. [19] recorded LSG nerve activity before and after RSN denervation, and they found that the 24hour average LSG nerve activity decreased from 275 mV-s at baseline to 233 mV-s 4 weeks after RSN denervation, which was associated with a reduction of paroxysmal atrial tachycardia episodes and duration. Recently, our study [20] showed that 3-hour RSN stimulation was able to increase LSG neuronal activity, and facilitate the incidence
124
B. Huang et al. / International Journal of Cardiology 179 (2015) 123–124
Fig. 1. A potential link between renal sympathetic nerve (RSN) and left stellate ganglion (LSG). Afferent signals from the RSN are able to affect nerve activity of LSG by modulating central sympathetic outflow. For example, activation of RSN may send excessive afferent signaling to the central sympathetic center, which in turn increases efferent neural inputs to LSG, inducing sympathetic nerve sprouting in the atrium and ventricle, which are important triggers for cardiac arrhythmias.
of ventricular arrhythmias during acute myocardial ischemia which was attenuated by LSG ablation. Taken together, these observations suggest that there is a potential link between LSG and RSN. Most of the brainstem regions received inputs from the renal afferents also involve in cardiovascular control [21], therefore afferent signals from the RSN are able to affect nerve activity of LSG by modulating central sympathetic outflow (Fig. 1). In conclusion, both LSG and RSN play an important role in cardiac arrhythmias and the potential link between them may be an important mechanism for cardiac arrhythmias. Acknowledgments This work was supported by the grants from the National Natural Science Foundation of China (81270339; 81300182; 81370281; 81270250; 81300181; 81400254), the Science and Technology Research Project of Wuhan (201306060201010271), the Natural Science Foundation of Hubei Province (2013CFB302), and the Fundamental Research Funds for the Central Universities (2012302020206; 2042012kf1099; 2042014kf0110). References [1] M.J. Shen, D.P. Zipes, Role of the autonomic nervous system in modulating cardiac arrhythmias, Circ. Res. 114 (2014) 1004–1021. [2] A.Y. Tan, S. Zhou, M. Ogawa, J. Song, M. Chu, H. Li, et al., Neural mechanisms of paroxysmal atrial fibrillation and paroxysmal atrial tachycardia in ambulatory canines, Circulation 118 (2008) 916–925. [3] J.M. Cao, L.S. Chen, B.H. KenKnight, T. Ohara, M.H. Lee, J. Tsai, et al., Nerve sprouting and sudden cardiac death, Circ. Res. 86 (2000) 816–821. [4] M. Swissa, S. Zhou, I. Gonzalez-Gomez, C.M. Chang, A.C. Lai, A.W. Cates, et al., Longterm subthreshold electrical stimulation of the left stellate ganglion and a canine model of sudden cardiac death, J. Am. Coll. Cardiol. 43 (2004) 858–864. [5] S. Zhou, B.C. Jung, A.Y. Tan, V.Q. Trang, G. Gholmieh, S.W. Han, et al., Spontaneous stellate ganglion nerve activity and ventricular arrhythmia in a canine model of sudden death, Heart Rhythm. 5 (2008) 131–139. [6] M.J. Shen, T. Shinohara, H.W. Park, K. Frick, D.S. Ice, E.K. Choi, et al., Continuous lowlevel vagus nerve stimulation reduces stellate ganglion nerve activity and paroxysmal atrial tachyarrhythmias in ambulatory canines, Circulation 123 (2011) 2204–2212.
[7] P.J. Schwartz, S.G. Priori, M. Cerrone, C. Spazzolini, A. Odero, C. Napolitano, et al., Left cardiac sympathetic denervation in the management of high-risk patients affected by the long-QT syndrome, Circulation 109 (2004) 1826–1833. [8] U. Baber, V.J. Howard, J.L. Halperin, E.Z. Soliman, X. Zhang, W. McClellan, et al., Association of chronic kidney disease with atrial fibrillation among adults in the United States: REasons for Geographic and Racial Differences in Stroke (REGARDS) Study, Circ. Arrhythm. Electrophysiol. 4 (2011) 26–32. [9] D. Dalal, J.S. de Jong, F.V. Tjong, Y. Wang, N. Bruinsma, L.R. Dekker, et al., Mild-tomoderate kidney dysfunction and the risk of sudden cardiac death in the setting of acute myocardial infarction, Heart Rhythm. 9 (2012) 540–545. [10] J.E. Davies, C.H. Manisty, R. Petraco, A.J. Barron, B. Unsworth, J. Mayet, et al., First-inman safety evaluation of renal denervation for chronic systolic heart failure: primary outcome from REACH-Pilot study, Int. J. Cardiol. 162 (2013) 189–192. [11] E. Pokushalov, A. Romanov, G. Corbucci, S. Artyomenko, V. Baranova, A. Turov, et al., A randomized comparison of pulmonary vein isolation with versus without concomitant renal artery denervation in patients with refractory symptomatic atrial fibrillation and resistant hypertension, J. Am. Coll. Cardiol. 60 (2012) 1163–1170. [12] B.F. Remo, M. Preminger, J. Bradfield, S. Mittal, N. Boyle, A. Gupta, et al., Safety and efficacy of renal denervation as a novel treatment of ventricular tachycardia storm in patients with cardiomyopathy, Heart Rhythm. 11 (2014) 541–546. [13] C. Ukena, A. Bauer, F. Mahfoud, J. Schreieck, H.R. Neuberger, C. Eick, et al., Renal sympathetic denervation for treatment of electrical storm: first-in-man experience, Clin. Res. Cardiol. 101 (2012) 63–67. [14] D. Linz, F. Mahfoud, U. Schotten, C. Ukena, H.R. Neuberger, K. Wirth, et al., Renal sympathetic denervation suppresses postapneic blood pressure rises and atrial fibrillation in a model for sleep apnea, Hypertension 60 (2012) 172–178. [15] D. Linz, K. Wirth, C. Ukena, F. Mahfoud, J. Poss, B. Linz, et al., Renal denervation suppresses ventricular arrhythmias during acute ventricular ischemia in pigs, Heart Rhythm. 10 (2013) 1525–1530. [16] Q. Zhao, S. Yu, H. Huang, Y. Tang, J. Xiao, Z. Dai, et al., Effects of renal sympathetic denervation on the development of atrial fibrillation substrates in dogs with pacing-induced heart failure, Int. J. Cardiol. 168 (2013) 1672–1673. [17] Z. Guo, Q. Zhao, H. Deng, Y. Tang, X. Wang, Z. Dai, et al., Renal sympathetic denervation attenuates the ventricular substrate and electrophysiological remodeling in dogs with pacing-induced heart failure, Int. J. Cardiol. 175 (2014) 185–186. [18] Y. Hou, J. Hu, S.S. Po, H. Wang, L. Zhang, F. Zhang, et al., Catheter-based renal sympathetic denervation significantly inhibits atrial fibrillation induced by electrical stimulation of the left stellate ganglion and rapid atrial pacing, PLoS One 8 (2013) e78218. [19] W.C. Tsai, Y.H. Chan, K. Chinda, W.T. Lai, S.F. Lin, P.S. Chen, Renal sympathetic denervation decreases the incidence of atrial tachycardia and improves baroreflex sensitivity in ambulatory dogs, Heart Rhythm. 11 (2014) S236. [20] B. Huang, L. Yu, B.J. Scherlag, S. Wang, B. He, K. Yang, et al., Left renal nerves stimulation facilitates ischemia-induced ventricular arrhythmia by increasing nerve activity of left stellate ganglion, J. Cardiovasc. Electrophysiol. (2014), http://dx.doi.org/10. 1111/jce.12498. [21] G.F. DiBona, Neural control of the kidney: past, present, and future, Hypertension 41 (2013) 621–624.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
A potential link between left stellate ganglion and renal sympathetic nerve: An important mechanism for cardiac arrhythmias? Bing Huang, Lilei Yu, Hong Jiang ⁎ Department of Cardiology, Renmin Hospital of Wuhan University, Cardiovascular Research Institute of Wuhan University, Wuhan, China
a r t i c l e
i n f o
Article history: Received 25 August 2014 Received in revised form 9 October 2014 Accepted 18 October 2014 Available online 22 October 2014 Keywords: Cardiac arrhythmias Autonomic nervous system Left stellate ganglion Renal sympathetic nerve
Atrial fibrillation is the most common arrhythmia in clinical practice, and ventricular arrhythmias represent the major mechanism of sudden cardiac death which is the leading cause of death in United States. It is now well established that the autonomic nervous system has an important role in the genesis and maintenance of these cardiac arrhythmias [1]. Therefore, modulating autonomic activity has been proposed as a method to potentially suppress cardiac arrhythmias. Increased nerve activity of left stellate ganglion (LSG) has been shown to contribute to the generation of cardiac arrhythmias. In a canine model of atrial pacing-induced atrial fibrillation, Tan et al. found that simultaneous sympathovagal discharges (recording from LSG and left vagal nerve) were common triggers of paroxysmal atrial tachyarrhythmias, which could be eliminated by cryoablation of extrinsic sympathovagal nerves [2]. Chen and colleagues [3,4] found that infusion of nerve growth factor or applying electrical stimulation to the LSG following myocardial infarction increased nerve density and ventricular arrhythmias. Direct nerve activity recording from the LSG in a canine model of sudden cardiac death showed that most ventricular tachycardia (86.3%) and sudden cardiac death were triggered by increased LSG nerve activity [5]. Interventions that decrease nerve activity of LSG are often antiarrhythmic. For example, inhibition of LSG nerve activity by chronic low-level vagus nerve stimulation significantly reduces the frequencies of paroxysmal atrial fibrillation (1.4/d versus 9.2/d in sham ⁎ Corresponding author at: Department of Cardiology, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuchang District, Wuhan City, Hubei Province 430060, China. E-mail address: [email protected] (H. Jiang).
http://dx.doi.org/10.1016/j.ijcard.2014.10.046 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
stimulation group) and atrial tachycardia (8.0/d versus 22.0/d in sham stimulation group) in ambulatory dogs [6]. Clinical evidence has shown that left cardiac sympathetic denervation, e.g. LSG resection, is able to prevent recurrence of malignant ventricular arrhythmias in high-risk patients [7]. These observations suggest that LSG plays an important role in the pathogenesis of cardiac arrhythmias. Renal sympathetic nerve (RSN), which has been identified as an important mediator of systemic sympathetic tone, may also be involved in the pathogenesis of cardiac arrhythmias. Clinical studies suggest that patients with chronic kidney disease, which is always accompanied by RSN activation, are associated with higher prevalence of atrial fibrillation [8] and sudden cardiac death [9] compared to those without chronic kidney disease. In recent years, RSN has become an interesting intervention target for the treatment of many diseases associated with chronic sympathetic activation [10], including cardiac arrhythmias [11–13]. Linz et al. showed that RSN denervation was able to prevent obstructive sleep apnea-associated atrial fibrillation [14] and acute ischemia-induced ventricular arrhythmias [15]. In a canine model of pacing-induced heart failure, Zhao and colleagues found that RSN denervation could suppress the atrial substrate remodeling and the atrial fibrillation vulnerability [16] as well as the ventricular substrate remodeling and the ventricular tachyarrhythmia vulnerability [17]. In a small human study [11], 9 of the 13 patients (69%) treated with circumferential pulmonary vein isolation (PVI) with RSN denervation had no longer atrial fibrillation recurrences at the 12-month post-ablation follow-up versus 4 of the 14 patients (29%) in the PVI-only group, indicating that RSN denervation significantly reduced atrial fibrillation recurrences when combined with PVI in patients with resistant hypertension. In addition, several case reports [12,13] have recently suggested that RSN denervation is an effective and safe therapy for the treatment of ventricular electrical storm. These results indicate that RSN may be a potential therapeutic target for cardiac arrhythmias. Recent studies showed that there is an association between LSG and RSN. Hou et al. [18] showed that RSN denervation could reduce atrial fibrillation inducibility and reverse atrial electrophysiological changes in a canine model of hyper-sympathetic activity induced by 3-hour LSG stimulation plus rapid atrial pacing. Tsai et al. [19] recorded LSG nerve activity before and after RSN denervation, and they found that the 24hour average LSG nerve activity decreased from 275 mV-s at baseline to 233 mV-s 4 weeks after RSN denervation, which was associated with a reduction of paroxysmal atrial tachycardia episodes and duration. Recently, our study [20] showed that 3-hour RSN stimulation was able to increase LSG neuronal activity, and facilitate the incidence
124
B. Huang et al. / International Journal of Cardiology 179 (2015) 123–124
Fig. 1. A potential link between renal sympathetic nerve (RSN) and left stellate ganglion (LSG). Afferent signals from the RSN are able to affect nerve activity of LSG by modulating central sympathetic outflow. For example, activation of RSN may send excessive afferent signaling to the central sympathetic center, which in turn increases efferent neural inputs to LSG, inducing sympathetic nerve sprouting in the atrium and ventricle, which are important triggers for cardiac arrhythmias.
of ventricular arrhythmias during acute myocardial ischemia which was attenuated by LSG ablation. Taken together, these observations suggest that there is a potential link between LSG and RSN. Most of the brainstem regions received inputs from the renal afferents also involve in cardiovascular control [21], therefore afferent signals from the RSN are able to affect nerve activity of LSG by modulating central sympathetic outflow (Fig. 1). In conclusion, both LSG and RSN play an important role in cardiac arrhythmias and the potential link between them may be an important mechanism for cardiac arrhythmias. Acknowledgments This work was supported by the grants from the National Natural Science Foundation of China (81270339; 81300182; 81370281; 81270250; 81300181; 81400254), the Science and Technology Research Project of Wuhan (201306060201010271), the Natural Science Foundation of Hubei Province (2013CFB302), and the Fundamental Research Funds for the Central Universities (2012302020206; 2042012kf1099; 2042014kf0110). References [1] M.J. Shen, D.P. Zipes, Role of the autonomic nervous system in modulating cardiac arrhythmias, Circ. Res. 114 (2014) 1004–1021. [2] A.Y. Tan, S. Zhou, M. Ogawa, J. Song, M. Chu, H. Li, et al., Neural mechanisms of paroxysmal atrial fibrillation and paroxysmal atrial tachycardia in ambulatory canines, Circulation 118 (2008) 916–925. [3] J.M. Cao, L.S. Chen, B.H. KenKnight, T. Ohara, M.H. Lee, J. Tsai, et al., Nerve sprouting and sudden cardiac death, Circ. Res. 86 (2000) 816–821. [4] M. Swissa, S. Zhou, I. Gonzalez-Gomez, C.M. Chang, A.C. Lai, A.W. Cates, et al., Longterm subthreshold electrical stimulation of the left stellate ganglion and a canine model of sudden cardiac death, J. Am. Coll. Cardiol. 43 (2004) 858–864. [5] S. Zhou, B.C. Jung, A.Y. Tan, V.Q. Trang, G. Gholmieh, S.W. Han, et al., Spontaneous stellate ganglion nerve activity and ventricular arrhythmia in a canine model of sudden death, Heart Rhythm. 5 (2008) 131–139. [6] M.J. Shen, T. Shinohara, H.W. Park, K. Frick, D.S. Ice, E.K. Choi, et al., Continuous lowlevel vagus nerve stimulation reduces stellate ganglion nerve activity and paroxysmal atrial tachyarrhythmias in ambulatory canines, Circulation 123 (2011) 2204–2212.
[7] P.J. Schwartz, S.G. Priori, M. Cerrone, C. Spazzolini, A. Odero, C. Napolitano, et al., Left cardiac sympathetic denervation in the management of high-risk patients affected by the long-QT syndrome, Circulation 109 (2004) 1826–1833. [8] U. Baber, V.J. Howard, J.L. Halperin, E.Z. Soliman, X. Zhang, W. McClellan, et al., Association of chronic kidney disease with atrial fibrillation among adults in the United States: REasons for Geographic and Racial Differences in Stroke (REGARDS) Study, Circ. Arrhythm. Electrophysiol. 4 (2011) 26–32. [9] D. Dalal, J.S. de Jong, F.V. Tjong, Y. Wang, N. Bruinsma, L.R. Dekker, et al., Mild-tomoderate kidney dysfunction and the risk of sudden cardiac death in the setting of acute myocardial infarction, Heart Rhythm. 9 (2012) 540–545. [10] J.E. Davies, C.H. Manisty, R. Petraco, A.J. Barron, B. Unsworth, J. Mayet, et al., First-inman safety evaluation of renal denervation for chronic systolic heart failure: primary outcome from REACH-Pilot study, Int. J. Cardiol. 162 (2013) 189–192. [11] E. Pokushalov, A. Romanov, G. Corbucci, S. Artyomenko, V. Baranova, A. Turov, et al., A randomized comparison of pulmonary vein isolation with versus without concomitant renal artery denervation in patients with refractory symptomatic atrial fibrillation and resistant hypertension, J. Am. Coll. Cardiol. 60 (2012) 1163–1170. [12] B.F. Remo, M. Preminger, J. Bradfield, S. Mittal, N. Boyle, A. Gupta, et al., Safety and efficacy of renal denervation as a novel treatment of ventricular tachycardia storm in patients with cardiomyopathy, Heart Rhythm. 11 (2014) 541–546. [13] C. Ukena, A. Bauer, F. Mahfoud, J. Schreieck, H.R. Neuberger, C. Eick, et al., Renal sympathetic denervation for treatment of electrical storm: first-in-man experience, Clin. Res. Cardiol. 101 (2012) 63–67. [14] D. Linz, F. Mahfoud, U. Schotten, C. Ukena, H.R. Neuberger, K. Wirth, et al., Renal sympathetic denervation suppresses postapneic blood pressure rises and atrial fibrillation in a model for sleep apnea, Hypertension 60 (2012) 172–178. [15] D. Linz, K. Wirth, C. Ukena, F. Mahfoud, J. Poss, B. Linz, et al., Renal denervation suppresses ventricular arrhythmias during acute ventricular ischemia in pigs, Heart Rhythm. 10 (2013) 1525–1530. [16] Q. Zhao, S. Yu, H. Huang, Y. Tang, J. Xiao, Z. Dai, et al., Effects of renal sympathetic denervation on the development of atrial fibrillation substrates in dogs with pacing-induced heart failure, Int. J. Cardiol. 168 (2013) 1672–1673. [17] Z. Guo, Q. Zhao, H. Deng, Y. Tang, X. Wang, Z. Dai, et al., Renal sympathetic denervation attenuates the ventricular substrate and electrophysiological remodeling in dogs with pacing-induced heart failure, Int. J. Cardiol. 175 (2014) 185–186. [18] Y. Hou, J. Hu, S.S. Po, H. Wang, L. Zhang, F. Zhang, et al., Catheter-based renal sympathetic denervation significantly inhibits atrial fibrillation induced by electrical stimulation of the left stellate ganglion and rapid atrial pacing, PLoS One 8 (2013) e78218. [19] W.C. Tsai, Y.H. Chan, K. Chinda, W.T. Lai, S.F. Lin, P.S. Chen, Renal sympathetic denervation decreases the incidence of atrial tachycardia and improves baroreflex sensitivity in ambulatory dogs, Heart Rhythm. 11 (2014) S236. [20] B. Huang, L. Yu, B.J. Scherlag, S. Wang, B. He, K. Yang, et al., Left renal nerves stimulation facilitates ischemia-induced ventricular arrhythmia by increasing nerve activity of left stellate ganglion, J. Cardiovasc. Electrophysiol. (2014), http://dx.doi.org/10. 1111/jce.12498. [21] G.F. DiBona, Neural control of the kidney: past, present, and future, Hypertension 41 (2013) 621–624.