Inspiratory- and expiratory-gated transcutaneous vagus nerve stimulation have different effects on heart rate in healthy subjects: preliminary results

Abstract

Purpose Transcutaneous auricular vagus nerve stimulation (taVNS) hasbeen considered for the treatment of sympathetically mediated disorders. However, the optimal mode of stimulation is unknown. This study aimed to compare the cardiovascular effects of respiratory-gated taVNS in healthy subjects. Methods The examination included expiratory-gated, inspiratory-gated, and non-respiratory-gated taVNS trials. Subjects were examined twice (the order of expiratory-and inspiratory-gated taVNS was changed). taVNS trials started with controlled breathing without stimulation (pre-stimulatory recording) followed by controlled breathing with taVNS (stimulatory recording). Synchronizing taVNS with the respiratory phase was computer-controlled. Heart rate (HR) was calculated from ECG. Systolic blood pressure (SBP) and systemic vascular resistance (SVR) were recorded continuously and noninvasively. Baroreflex sensitivity based on rising (BRS-UP) or falling SBP sequences (BRS-DOWN) or all sequences (BRS-ALL) and heart rate variability (HRV) were analyzed. Results Seventy-two taVNS trials were obtained from 12 subjects (age 23 ± 3 years). Pre-stimulatory HR correlated with change in HR (r = − 0.25) and SVR (r = 0.24, both p < 0.05). There were no differences between three stimulatory conditions in (1) the changes of hemodynamic parameters, (2) BRS-UP and BRS-ALL, or (3) HRV indices (all p > 0.20). However, in the group of high pre-stimulatory HR trials, HR change differed between inspiratory-gated (0.11 ± 0.53%) and both expiratorygated (− 1.30 ± 0.58%, p = 0.06) and non-respiratory-gated taVNS (− 1.69 ± 0.65, p = 0.02). BRS-DOWN was higher in inspiratory-vs. non-respiratory-gated taVNS (15.4 ± 1.3 vs. 14.1 ± 0.9 ms/mmHg, p = 0.03). Conclusions Expiratory-gated and non-respiratory-gated taVNS exert clear cardioinhibitory effects in healthy subjects with high pre-stimulatory HR, whereas inspiratory-gated taVNS does not affect HR. Cardiac and vascular effects of taVNS depend on pre-stimulatory HR.

Does transcutaneous auricular vagus nerve stimulation affect vagally mediated heart rate variability? A living and interactive Bayesian meta‐analysis

“…Additionally, four studies measured vmHRV, but reported the results insufficiently to derive estimates for the meta-analysis and thus were excluded. One study had neither a sham condition nor a vmHRV baseline measurement and was thus excluded (Paleczny et al, 2021). Furthermore, we excluded two studies which did not use taVNS but transcutaneous cervical vagus nerve stimulation (Brock et al, 2017) or transcutaneous electrical nerve stimulation on cervical acupuncture points (Chan et al, 2012), respectively.…”

International Consensus Based Review and Recommendations for Minimum Reporting Standards in Research on Transcutaneous Vagus Nerve Stimulation (Version 2020)

“…Other more physiologically oriented studies have investigated the influence of tVNS on cardiac activity (Brock et al, 2017;De Couck et al, 2017;Lamb et al, 2017;Gancheva et al, 2018;Borges et al, 2019;Bretherton et al, 2019;Koenig et al, 2019;Paleczny et al, 2019;Tobaldini et al, 2019;Tran et al, 2019); autonomic outflow (Sclocco et al, 2017); sympathetic nerve activity (Clancy et al, 2014) or cardiac baroreflex sensitivity (Antonino et al, 2017); atrial fibrillation (Stavrakis et al, 2015); cardiac mechanical function (Tran et al, 2019); vagal sensory evoked potentials (Fallgatter et al, 2003(Fallgatter et al, , 2005Polak et al, 2009;Leutzow et al, 2013); persistent hiccups (Schulz-Stübner and Kehl, 2011); visual bistable perception (Keute et al, 2019a); nociceptive neuromodulation (Napadow et al, 2012;Busch et al, 2013;Laqua et al, 2014;Usichenko et al, 2017b;Janner et al, 2018); tumor necrosis factor-alpha (Brock et al, 2017); hepatic energy metabolism (Gancheva et al, 2018); whole blood culture-derived cytokines and chemokines (Lerman et al, 2016); salivary hormones (Ventura-Bort et al, 2018;Koenig et al, 2019;Warren et al, 2019); pupil diameter (Warren et al, 2019); gastroduodenal or gastrointestinal motility (Frøkjaer et al, 2016;Juel et al, 2017); muscle activity in the gastrointest...…”

Does non-invasive vagus nerve stimulation affect heart rate variability? A living and interactive Bayesian meta-analysis

“…Additionally, four studies measured HRV, but reported the results insufficiently to derive estimates for the meta-analysis and thus were excluded. One study had neither a sham condition nor an HRV baseline measurement and was thus excluded (Paleczny et al, 2019). Furthermore, we excluded two studies which did not use taVNS but transcutaneous cervical vagus nerve stimulation (Brock et al, 2017) or transcutaneous electrical nerve stimulation on cervical acupuncture points (Chan et al, 2012), respectively.…”