A framework for the interpretation of heart rate variability applied to transcutaneous auricular vagus nerve stimulation and osteopathic manipulation.

Reports on autonomic responses to transcutaneous auricular vagus nerve stimulation (taVNS) and osteopathic manipulative techniques have been equivocal, partly due to inconsistent interpretation of heart rate variability (HRV). We developed a mechanistic framework for the interpretation of HRV based on a model of sinus node automaticity that considers autonomic effects on Phase 3 repolarization and Phase 4 depolarization of the sinoatrial action potential. The model was applied to HRV parameters calculated from ECG recordings (healthy adult humans, both genders) before (30 min), during (15 min), and after (30 min) a time control intervention (rest, n = 23), taVNS (10 Hz, 300 µs, 1-2 mA, cymba concha, left ear, n = 12), or occipitoatlantal decompression (OA-D, n = 14). The experimental protocol was repeated on 3 consecutive days. The model simulation revealed that low frequency (LF) HRV best predicts sympathetic tone when calculated from heart rate time series, while high frequency (HF) HRV best predicts parasympathetic tone when calculated from heart period time series. Applying our model to the HRV responses to taVNS and OA-D, revealed that taVNS increases cardiac parasympathetic tone, while OA-D elicits a mild decrease in cardiac sympathetic tone.

Transcutaneous auricular vagus nerve stimulation augments postprandial inhibition of ghrelin.

Vagus nerve stimulation (VNS) facilitates weight loss in animals and patients treated with VNS for depression or epilepsy. Likewise, chronic transcutaneous auricular VNS (taVNS) reduces weight gain and improves glucose tolerance in Zucker diabetic fatty rats. If these metabolic effects of taVNS observed in rats translate to humans is unknown. Therefore, the hypothesis of this study was that acute application of taVNS affects glucotropic and orexigenic hormones which could potentially facilitate weight loss and improve glucose tolerance if taVNS were applied chronically. In two single-blinded randomized cross-over protocols, blood glucose levels, plasma concentrations of insulin, C-peptide, glucagon, leptin, and ghrelin, together with heart rate variability and baroreceptor-heart rate reflex sensitivity were determined before and after taVNS (left ear, 10 Hz, 300 µs, 2.0-2.5 mA, 30 min) or sham-taVNS (electrode attached to ear with the stimulator turned off). In a first protocol, subjects (n = 16) were fasted throughout the protocol and in a second protocol, subjects (n = 10) received a high-calorie beverage (220 kCal) after the first blood sample, just before initiation of taVNS or sham-taVNS. No significant effects of taVNS on heart rate variability and baroreceptor-heart rate reflex sensitivity and only minor effects on glucotropic hormones were observed. However, in the second protocol taVNS significantly lowered postprandial plasma ghrelin levels (taVNS: -115.5 ± 28.3 pg/ml vs. sham-taVNS: -51.2 ± 30.6 pg/ml, p < 0.05). This finding provides a rationale for follow-up studies testing the hypothesis that chronic application of taVNS may reduce food intake through inhibition of ghrelin and, therefore, may indirectly improve glucose tolerance through weight loss.