Blood Pressure Modulation With Low-Intensity Focused Ultrasound Stimulation to the Vagus Nerve: A Pilot Animal Study
Ning Ji, Wan-Hua Lin, Fei Chen, Lisheng Xu, Jianping Huang, Guanglin Li
Frontiers in Neuroscience 2020, 14 · 10.3389/fnins.2020.586424
Abstract
Objective For hypertensive individuals, their blood pressure (BP) is often managed by taking medications. However, antihypertensive drugs might cause adverse effects such as congestive heart failure and are ineffective in significant numbers of the hypertensive population. As an alternative method for hypertension management, non-drug devices-based neuromodulation approaches such as functional electrical stimulation (FES) have been proposed. The FES approach requires the implantation of a stimulator into the body. One recently emerging technique, called low-intensity focused ultrasound stimulation (FUS), has been proposed to non-invasively modulate neural activities. In this pilot study, the feasibility of adopting low-intensity FUS neuromodulation for BP regulation was investigated using animal models. Methods A FUS system was developed for BP modulation in rabbits. For each rabbit, the low-intensity FUS with different acoustic intensities was used to stimulate its exposed left vagus nerve, and the BP waveform was synchronously recorded in its right common carotid artery. The effects of the different FUS intensities on systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MAP), and heart rate (HR) were extensively examined from the BP recordings. Results The results demonstrated that the proposed FUS method could successfully induce changes in SBP, DBP, MAP, and HR values. When increasing acoustic intensities, the values of SBP, DBP, and MAP would tend to decrease more substantially. Conclusion The findings of this study suggested that BP could be modulated through the FUS, which might provide a new way for non-invasive and non-drug management of hypertension.
Abstract via europepmc.
Exposures
Exposure 1: FUS to exposed left vagus nerve, intensity/duty-cycle sweep
Target: vagus nerve — “left vagus nerve”
Device: other named manufacturer
| Waveform | continuous, pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 3,700 | ✓✓✓⚑ |
| Pulse duration (ms) | 0.3, 0.5, 0.7swept | ✓✓✓ |
| Pulse repetition frequency (Hz) | 1,000 | ✓✓✓ |
| Duty cycle (%) | 30, 50, 70, 100swept | ✓✓✓ |
| Sonication duration (s) | 5 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | 18, 48.5, 87.3swept | ✓✓✓⚑ |
| Free-field Ispta (W/cm²) | 5.4, 87.3swept | ✓✓✓ |
| In-situ estimate | not reported | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
Fundamental frequency, PRF, sonication duration (SD) and inter-stimulus interval (ISI) were fixed at 3.7 MHz, 1 kHz, 5 s and 1 s respectively; tone-burst duration (TBD) was varied to give duty cycles of 30, 50, 70 and 100% at each of three Isppa levels (18.0, 48.5, 87.3 W/cm^2). For each trial the FUS was applied for about 20 s in total (repeated 5-s trains at 1-s ISI), followed by a ~60 s wait for BP to return to baseline. Trial order was pseudo-randomized and balanced across animals, with repeated trials per parameter set.
Flags from extraction
exposures[0].fundamental_frequency_khz— Paper also preliminarily screened 548 kHz and 1.05 MHz transducers ('little' and 'slight' BP response respectively) but reported no quantitative sonication parameters or BP data for those, so only the systematically studied 3.7 MHz condition is recorded as an exposure.exposures[0].timing.waveform— 100% duty cycle condition is continuous wave while 30/50/70% conditions are pulsed; both are listed since this is one exposure with a duty-cycle sweep.exposures[0].free_field.isppa_w_cm2— Domain of the acoustic-field hydrophone measurement (water tank vs. in situ at the nerve) is not explicitly stated; recorded as free_field on the basis that it was measured with a scanning hydrophone system, but the paper does not use the word 'water' or 'free field' explicitly for this measurement.