Dose-Optimization of Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS) for Blood Pressure Modulation in Hypertensive Patients

Jessica Stowell1, Ronald Garcia2, Rachel Staley1, Roberta Sclocco3, Harrison Fisher4, Vitaly Napadow3, Jill Goldstein5, Riccardo Barbieri6
1Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, 2Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School. Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, 3Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Department of Radiology, Logan University, 4Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, 5Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Women, Heart and Brain Global Initiative, Massachusetts General Hospital, Harvard Medical School, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, 6Politecnico di Milano

Abstract

Introduction: Reduced cardiac vagal activity has been proposed as an etiological mechanism for hypertension. Non-invasive brain stimulation methods targeting the vagus nerve and brain regions regulating parasympathetic tone could have the potential to modulate cardiovascular activity in subjects with hypertension. The objective of this study was to characterize, in hypertensive subjects, blood pressure responses to respiratory-gated auricular vagal nerve stimulation (RAVANS) over a wide range of stimulation frequencies in order to define the optimal protocol for treatment of hypertension.

Methods: Twelve hypertensive subjects (52.5±6.0 years, 8 females) were enrolled in this study. Participants underwent five randomized stimulation sessions, during which they received exhalatory-gated stimulation at frequencies of 2, 10, 25, and 100 Hz (pulse width:300μs) or sham stimulation. Electrodes were placed over vagal-innervated auricular regions (cymba concha) in the left ear, and stimulation amplitude was calibrated to an intensity that produced a moderate, non-painful sensation. A continuous blood pressure signal was collected during 30-minute stimulation period and for a 10-minute recovery period using a Finometer device (Finapress Medical System, the Netherlands). Blood pressure levels were computed over the recovery and stimulation periods by using LabChart (ADInstruments, New Zealand).

Results: Significant reductions in diastolic (72.4±9.1 mmHg vs 78.6 ± 7.9 mmHg, p=0.04) and mean arterial pressure (94.1±9.6 mmHg vs 100.3±9.0, p=0.04) values were observed during RAVANS stimulation at 100 Hz compared to baseline. The difference between systolic arterial pressure values during stimulation and baseline also revealed a significant difference between the 100 Hz session compared to sham stimulation (-5.0±10.5 mmHg vs 2.7±7.5, p=0.01). Evaluation of other stimulation frequencies did not reveal significant results.

Conclusions: Our results support that RAVANS has a frequency-dependent effect on the modulation of arterial blood pressure levels of hypertensive subjects. Future longitudinal studies should examine the potential therapeutic effects of this technique in hypertension.