Korean Circulation Journal

The Korean Society of Cardiology (대한심장학회)
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Cervical Vagal Nerve Stimulation Activates the Stellate Ganglion in Ambulatory Dogs

  • Rhee, Kyoung-Suk (Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine) ;
  • Hsueh, Chia-Hsiang (Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine) ;
  • Hellyer, Jessica A. (Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine) ;
  • Park, Hyung Wook (Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine) ;
  • Lee, Young Soo (Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine) ;
  • Garlie, Jason (Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine) ;
  • Onkka, Patrick (Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine) ;
  • Doytchinova, Anisiia T. (Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine) ;
  • Garner, John B. (Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine) ;
  • Patel, Jheel (Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine) ;
  • Chen, Lan S. (Department of Neurology, Indiana University School of Medicine) ;
  • Fishbein, Michael C. (Department of Pathology and Laboratory Medicine, The David Geffen School of Medicine) ;
  • Everett, Thomas (Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine) ;
  • Lin, Shien-Fong (Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine) ;
  • Chen, Peng-Sheng (Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine)
  • Received : 2014.10.19
  • Accepted : 2015.01.08
  • Published : 2015.03.30
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Abstract

Background and Objectives: Recent studies showed that, in addition to parasympathetic nerves, cervical vagal nerves contained significant sympathetic nerves. We hypothesized that cervical vagal nerve stimulation (VNS) may capture the sympathetic nerves within the vagal nerve and activate the stellate ganglion. Materials and Methods: We recorded left stellate ganglion nerve activity (SGNA), left thoracic vagal nerve activity (VNA), and subcutaneous electrocardiogram in seven dogs during left cervical VNS with 30 seconds on-time and 30 seconds off time. We then compared the SGNA between VNS on and off times. Results: Cervical VNS at moderate (0.75 mA) output induced large SGNA, elevated heart rate (HR), and reduced HR variability, suggesting sympathetic activation. Further increase of the VNS output to >1.5 mA increased SGNA but did not significantly increase the HR, suggesting simultaneous sympathetic and parasympathetic activation. The differences of integrated SGNA and integrated VNA between VNS on and off times (${\Delta}SGNA$) increased progressively from 5.2 mV-s {95% confidence interval (CI): 1.25-9.06, p=0.018, n=7} at 1.0 mA to 13.7 mV-s (CI: 5.97-21.43, p=0.005, n=7) at 1.5 mA. The difference in HR (${\Delta}HR$, bpm) between on and off times was 5.8 bpm (CI: 0.28-11.29, p=0.042, n=7) at 1.0 mA and 5.3 bpm (CI 1.92 to 12.61, p=0.122, n=7) at 1.5 mA. Conclusion: Intermittent cervical VNS may selectively capture the sympathetic components of the vagal nerve and excite the stellate ganglion at moderate output. Increasing the output may result in simultaneously sympathetic and parasympathetic capture.

Keywords

References

  1. Terry R. Vagus nerve stimulation: a proven therapy for treatment of epilepsy strives to improve efficacy and expand applications. Conf Proc IEEE Eng Med Biol Soc 2009;2009:4631-4.
  2. Premchand RK, Sharma K, Mittal S, et al. Autonomic regulation therapy via left or right cervical vagus nerve stimulation in patients with chronic heart failure: results of the ANTHEM-HF trial. J Card Fail 2014;20:808-16. https://doi.org/10.1016/j.cardfail.2014.08.009
  3. Zannad F, De Ferrari GM, Tuinenburg AE, et al. Chronic vagal stimulation for the treatment of low ejection fraction heart failure: results of the neural cardiac therapy for heart failure (NECTAR-HF) randomized controlled trial. Eur Heart J 2014;36:425-33.
  4. De Ferrari GM, Crijns HJ, Borggrefe M, et al. Chronic vagus nerve stimulation:a new and promising therapeutic approach for chronic heart failure. Eur Heart J 2011;32:847-55. https://doi.org/10.1093/eurheartj/ehq391
  5. Klein HU, Ferrari GM. Vagus nerve stimulation: a new approach to reduce heart failure. Cardiol J 2010;17:638-44.
  6. Sabbah HN. Electrical vagus nerve stimulation for the treatment of chronic heart failure. Cleve Clin J Med 2011;78 Suppl 1:S24-9.
  7. Onkka P, Maskoun W, Rhee KS, et al. Sympathetic nerve fibers and ganglia in canine cervical vagus nerves: localization and quantitation. Heart Rhythm 2013;10:585-91. https://doi.org/10.1016/j.hrthm.2012.12.015
  8. Kawagishi K, Fukushima N, Yokouchi K, Sumitomo N, Kakegawa A, Moriizumi T. Tyrosine hydroxylase-immunoreactive fibers in the human vagus nerve. J Clin Neurosci 2008;15:1023-6. https://doi.org/10.1016/j.jocn.2007.08.032
  9. Seki A, Green HR, Lee TD, et al. Sympathetic nerve fibers in human cervical and thoracic vagus nerves. Heart Rhythm 2014;11:1411-7. https://doi.org/10.1016/j.hrthm.2014.04.032
  10. Schwartz PJ, Pagani M, Lombardi F, Malliani A, Brown AM. A cardiocardiac sympathovagal reflex in the cat. Circ Res 1973;32:215-20. https://doi.org/10.1161/01.RES.32.2.215
  11. Shen MJ, Shinohara T, Park HW, et al. Continuous low-level vagus nerve stimulation reduces stellate ganglion nerve activity and paroxysmal atrial tachyarrhythmias in ambulatory canines. Circulation 2011;123:2204-12. https://doi.org/10.1161/CIRCULATIONAHA.111.018028
  12. Shen MJ, Hao-Che Chang, Park HW, et al. Low-level vagus nerve stimulation upregulates small conductance calcium-activated potassium channels in the stellate ganglion. Heart Rhythm 2013;10:910-5. https://doi.org/10.1016/j.hrthm.2013.01.029
  13. Adelman JP, Maylie J, Sah P. Small-conductance Ca2+-activated K+ channels: form and function. Annu Rev Physiol 2012;74:245-69. https://doi.org/10.1146/annurev-physiol-020911-153336
  14. Ogawa M, Zhou S, Tan AY, et al. Left stellate ganglion and vagal nerve activity and cardiac arrhythmias in ambulatory dogs with pacing-induced congestive heart failure. J Am Coll Cardiol 2007;50:335-43. https://doi.org/10.1016/j.jacc.2007.03.045
  15. Tan AY, Zhou S, Ogawa M, et al. Neural mechanisms of paroxysmal atrial fibrillation and paroxysmal atrial tachycardia in ambulatory canines. Circulation 2008;118:916-25. https://doi.org/10.1161/CIRCULATIONAHA.108.776203
  16. Robinson EA, Rhee KS, Doytchinova A, et al. Estimating sympathetic tone by recording subcutaneous nerve activity in ambulatory dogs. J Cardiovasc Electrophysiol 2015;26:70-8. https://doi.org/10.1111/jce.12508
  17. Mizeres NJ. The anatomy of the autonomic nervous system in the dog. Am J Anat 1955;96:285-318. https://doi.org/10.1002/aja.1000960205
  18. Ellison JP, Williams TH. Sympathetic nerve pathways to the human heart, and their variations. Am J Anat 1969;124:149-62. https://doi.org/10.1002/aja.1001240203
  19. Armour JA, Hageman GR, Randall WC. Arrhythmias induced by local cardiac nerve stimulation. Am J Physiol 1972;223:1068-75.
  20. Dicarlo L, Libbus I, Amurthur B, Kenknight BH, Anand IS. Autonomic regulation therapy for the improvement of left ventricular function and heart failure symptoms: the ANTHEM-HF study. J Card Fail 2013;19:655-60. https://doi.org/10.1016/j.cardfail.2013.07.002
  21. Burashnikov A, Antzelevitch C. Reinduction of atrial fibrillation immediately after termination of the arrhythmia is mediated by late phase 3 early afterdepolarization-induced triggered activity. Circulation 2003;107:2355-60. https://doi.org/10.1161/01.CIR.0000065578.00869.7C
  22. Patterson E, Po SS, Scherlag BJ, Lazzara R. Triggered firing in pulmonary veins initiated by in vitro autonomic nerve stimulation. Heart Rhythm 2005;2:624-31. https://doi.org/10.1016/j.hrthm.2005.02.012
  23. Goldberger AL, Pavelec RS. Vagally-mediated atrial fibrillation in dogs:conversion with bretylium tosylate. Int J Cardiol 1986;13:47-55. https://doi.org/10.1016/0167-5273(86)90078-1
  24. del Negro CA, Hsiao CF, Chandler SH. Outward currents influencing bursting dynamics in guinea pig trigeminal motoneurons. J Neurophysiol 1999;81:1478-85. https://doi.org/10.1152/jn.1999.81.4.1478
  25. Kohler M, Hirschberg B, Bond CT, et al. Small-conductance, calciumactivated potassium channels from mammalian brain. Science 1996;273:1709-14. https://doi.org/10.1126/science.273.5282.1709

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