The Use of Noninvasive Vagal Nerve Stimulation to Inhibit Sympathetically Induced Sinus Node Acceleration: A Potential Therapeutic Approach for Inappropriate Sinus Tachycardia

J Cardiovasc Electrophysiol. 2016 Feb;27(2):217-23. doi: 10.1111/jce.12859. Epub 2015 Nov 23.

Abstract

Background: Hyperactivity of the cardiac sympathetic nervous system may underlie the pathogenesis of inappropriate sinus tachycardia (IST). Studies have proven that cervical vagal stimulation could inhibit stellate ganglion neural activity.

Subjects: To investigate whether noninvasive vagal nerve stimulation (NVNS) could inhibit sympathetically induced sinus node acceleration by reducing right stellate ganglion (RSG) neural activity.

Methods: Sixteen anesthetized dogs were randomly divided into NVNS group (with NVNS, n = 8) and control group (with sham NVNS, n = 8). NVNS was delivered to the vagus nerve innervating at the right tragus with a voltage of 80% below the threshold, the minimal voltage to slow the sinus rate or atrioventricular conduction. The maximal sinus rate accelerations induced by high-frequency stimulation (HFS) of RSG and RSG neural activity were measured at baseline and 3 hours after NVNS. At the end, SK2, c-fos, and NGF protein expression in RSG were examined in both groups.

Results: Compared to baseline, the maximal sinus node acceleration induced by RSG stimulation and the RSG neural activity were both significantly attenuated after 3 hours of NVNS (P < 0.05 for both). However, these indices did not change significantly in the control group (P > 0.05). SK2 expression in RSG was significantly higher and c-fos and NGF expressions were significantly lower in the NVNS group than those in the control group (P < 0.05).

Conclusion: Noninvasive vagal nerve stimulation may suppress RSG activity possibly by modulating SK2, c-fos, and NGF expressions in RSG, thus inhibiting sympathetically induced sinus node acceleration.

Keywords: autonomic nervous system; inappropriate sinus tachycardia; noninvasive vagal nerve stimulation; parasympathetic nervous system; right stellate ganglion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Dogs
  • Heart Rate*
  • Nerve Growth Factor / genetics
  • Nerve Growth Factor / metabolism
  • Proto-Oncogene Proteins c-fos / genetics
  • Proto-Oncogene Proteins c-fos / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Sinoatrial Node / innervation*
  • Small-Conductance Calcium-Activated Potassium Channels / genetics
  • Small-Conductance Calcium-Activated Potassium Channels / metabolism
  • Stellate Ganglion / metabolism
  • Stellate Ganglion / physiopathology*
  • Tachycardia, Sinus / etiology
  • Tachycardia, Sinus / genetics
  • Tachycardia, Sinus / metabolism
  • Tachycardia, Sinus / physiopathology
  • Tachycardia, Sinus / therapy*
  • Time Factors
  • Vagus Nerve Stimulation / methods*

Substances

  • Proto-Oncogene Proteins c-fos
  • RNA, Messenger
  • Small-Conductance Calcium-Activated Potassium Channels
  • Nerve Growth Factor