Acute Effects of Respiratory-Gated Auricular Vagal Afferent Nerve Stimulation in the Modulation of Blood Pressure in Hypertensive Patients

Harrison Fisher1, Jessica Stowell2, Ronald Garcia3, Roberta Sclocco4, Jill Goldstein5, Vitaly Napadow6, Riccardo Barbieri7
1Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, 2Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, 3Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School. Connors Center for Women's Health, Brigham and Women's Hospital, Harvard Medical School., 4Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital. Department of Radiology, Logan University, 5Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School. Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School. 3Division of Women’s Health, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, 6Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School. Department of Radiology, Logan University, 7Politecnico di Milano

Abstract

Background: Previous studies have demonstrated a link between cardiac autonomic dysregulation and the development and progression of hypertension. Transcutaneous vagus nerve stimulation has previously been shown to regulate parasympathetic tone, thus providing a potential therapeutic tool for cardiovascular disorders associated with autonomic imbalance. In this study, our aim was to evaluate the acute effects of a novel, non-invasive, respiratory-gated auricular vagal afferent nerve stimulation (RAVANS) technique in the modulation of blood pressure in hypertensive patients. Methods: Eighteen hypertensive subjects (53.6±6.3 years, 9 males) were enrolled in this study. Participants underwent three stimulation sessions, during which they received either sham, low-intensity, or medium-intensity stimulation in randomized order. Electrodes were placed over vagal-innervated auricular regions. RAVANS was delivered at 25 Hz (duration:1s, pulse width:15ms) and gated to exhalation, with current intensity set to achieve a non-painful, mild or moderate sensation. Sham stimulation was delivered with the current generator shut off, with subjects blinded to stimulus condition. Continuous blood pressure signal was collected during 15-minute baseline, stimulation, and recovery windows. Results: During stimulation, the percent decrease of median systolic blood pressure from baseline was significantly higher during RAVANS (medium-intensity) when compared to sham (p < 0.05). Furthermore, a two-way ANOVA revealed a significant interaction between Intervention and Phase for changes in median systolic blood pressure (F(4) = 2.89, p < 0.05). Pairwise post hoc testing revealed that this effect was largely driven by the Recovery Phase following RAVANS where median Systolic BP significantly decreased in the last 5 minutes compared to sham (p < 0.05).  Conclusions: Our results indicate that exhalatory-gated RAVANS has significant acute modulatory effects on systolic blood pressure levels of hypertensive patients, both during and following stimulation. Further longitudinal studies will be required to validate these findings and evaluate the therapeutic potential of this electroceutical.