Abstract
PURPOSE: Transcutaneous auricular vagus nerve stimulation (taVNS) has been 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 expiratory-gated (- 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.