Impact of Respiratory-Gated Transcutaneous Vagus Nerve Stimulation on Cardiovagal Regulation in Hypertension

Rachel Staley, BA

Massachusetts General Hospital
Impact of Respiratory-Gated Transcutaneous Vagus Nerve Stimulation on Cardiovagal Regulation in Hypertension

Scientific Abstract


Background: Hypertension is a risk factor for developing cardiovascular disease (CVD) and is associated with numerous disorders of the brain. Studies have demonstrated an association between reduced cardiac vagal tone, driven by the brain, and worse cardiovascular prognosis in hypertension. Thus, developing a therapeutic targeted to the vagus nerve could have implications for CVD risk and comorbidity with brain disorders. We present here a pilot study to identify effects of a non-invasive Respiratory-gated Auricular Vagus Afferent Nerve Stimulation (RAVANS) on cardiac tone (operationalized as heart rate variability (HRV)) in hypertensive patients.

Methods: 20 hypertensive subjects (57.3±6.2 years; 11 females) were randomized to receive either active RAVANS or sham stimulation for 5 consecutive days (Sessions 1-5). All subjects were on stable doses of antihypertensives for ≥30 days prior to enrollment. Electrodes were placed over a vagal-innervated region on the outer ear and RAVANS was delivered at 25Hz with a moderate intensity. Each stimulation session consisted of a 30-min stimulation period with 10- min baseline and recovery periods. Participants were also evaluated 5 and 10 days after the last stimulation session (Sessions 6 and 7). ECG and heart rate signals were collected throughout all visits. Percent changes in the relative power of the high-frequency band (HF power (%)), an HRV index of cardiovagal activity, were calculated to compare Sessions 5, 6, and 7 to Session 1. General linear models were implemented to evaluate the effects of RAVANS versus sham. Baseline HF values and sex were included in the models and adjusted regression coefficients were calculated.

Results: RAVANS had a significant effect on increasing HF power (%) during the recovery period of Sessions 5 (β=179.81, t(39)=2.92, p=0.014, Adj R2=0.57), 6 (β=197.46, t(39)=2.60, p=0.027, Adj R2=0.24), and 7 (β=144.67, t(39)=2.40, p=0.037, Adj R2=0.19) in comparison to sham.

Conclusions: Repeated administration of RAVANS at 25Hz effectively upregulates cardiovagal activity in hypertensive subjects, with effects lasting up to 10 days after the last stimulation session.

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research Areas


Rachel Staley, BA, Ronald G. Garcia, MD, PhD, Jessica Stowell, BS, Roberta Sclocco, PhD, Harrison Fisher, BS, Vitaly Napadow, PhD, LicAc, Riccardo Barbieri, PhD, Jill Goldstein, PhD

Principal Investigator

Jill Goldstein, PhD

Affiliated Website