Low-intensity pulsed ultrasound elevates blood pressure for shock
Chenrui Wu, Yu Tian, Tao Liu, Shuo An, Yu Qian, Chuang Gao, Jiangyuan Yuan, Mingqi Liu, Meng Nie, Weiwei Jiang, Zhuang Sha, Chuanxiang Lv, Qiang Liu, Xiaochun Wang, Sheng Zhou, Rongcai Jiang
Science Advances 2025, 11 · 10.1126/sciadv.ads6947
Abstract
Fluid replacement is the primary treatment for life-threatening shock but is challenging in harsh environments. This study explores low-intensity pulsed ultrasound (LIPUS) as a resuscitation strategy. Cervical LIPUS stimulation effectively elevated blood pressure in shocked rats. It also improved cerebral and multiorgan perfusion. Mechanistically, LIPUS activated pathways related to sympathetic nerve excitation and vascular smooth muscle contraction, increasing plasma catecholamines and stimulating blood pressure-regulating neural nuclei. Partial sympathetic nerve transection reduced LIPUS efficacy, while complete inhibition of these nuclei abolished the response. Preliminary clinical trials demonstrated LIPUS's ability to raise blood pressure in shock patients. The findings suggest that LIPUS enhances sympathetic nerve activity and activates blood pressure-regulating nuclei, offering a noninvasive, neuromodulation-based approach to shock treatment. This method holds potential for improving blood pressure and organ perfusion in shock patients, especially in resource-limited environments.
Abstract via europepmc.
Exposures
Exposure 1: Cervical carotid triangle LIPUS stimulation in rats (dose-response and mechanistic experiments)
Target: other — “cervical carotid triangle (overlying sympathetic nerve trunk, vagus nerve and carotid sinus nerve region)”
Device: other named manufacturer · DJO FRANCE SAS
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 3,000 | ✓✓✓ |
| Pulse duration (ms) | 1 | ✓✓✓⚑ |
| Pulse repetition frequency (Hz) | 100 | ✓✓✓ |
| Duty cycle (%) | 50pulse duration × PRF gives 10%, which disagrees with the stated value | ✓✓✓ |
| Sonication duration (s) | 600 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| 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 | |
| Isppa, domain unspecified (W/cm²) | 1, 2, 3swept | ✓✓✓ |
A minimum of 5 min of baseline BP/ECG monitoring was performed before cervical LIPUS stimulation, followed by 10 min of stimulation, and 5 min of continued monitoring after stopping. In the dose-response experiment, Isppa was set to 1, 2, or 3 W/cm2 (5 rats per group); 2 W/cm2 was selected for subsequent mechanistic experiments (sympathectomy, HRV, metabolomics, fMRI, hemorrhagic shock).
Exposure 2: Cervical carotid triangle LIPUS stimulation in shock patients and healthy volunteers
Target: other — “cervical carotid triangle (overlying sympathetic trunk / carotid sinus nerve region), left neck anterior to sternocleidomastoid”
Device: not reported
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 3,000 | ✓✓✓ |
| Pulse duration (ms) | not reportedimplied by duty cycle ÷ PRF: 5 ms (not stated by the paper) | ⚑ |
| Pulse repetition frequency (Hz) | 100 | ✓✓✓ |
| Duty cycle (%) | 50 | ✓✓✓ |
| Sonication duration (s) | 300 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| 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 | |
| Isppa, domain unspecified (W/cm²) | 3 | ✓✓✓ |
Cervical LIPUS was applied via a 5-cm2 ultrasound generator to the left carotid triangle. All participants (12 shock patients; 5 healthy volunteers) underwent a 5-min stimulus, with BP measurements recorded for a minimum of 5 min before and after the stimulus.
Flags from extraction
n_subjects— Paper spans many different rat cohorts (5 per intensity group; 9 vs 8 per HRV/metabolomics group; 5-6 per mechanistic sub-experiment) plus 12 shock patients and 5 healthy volunteers; no single overall total number of subjects exposed to ultrasound is stated.n_sessions_per_subject— Procedure describes a single baseline-stimulation-poststimulation timeline per animal/patient, but no explicit numeric statement of sessions per subject is given.exposures[0].timing.pulse_duration_ms— Stated pulse duration (1 ms) is inconsistent with the stated duty cycle (50%) and PRF (100 Hz), which would imply a 5 ms pulse; recorded as stated per the burst rule (possible typo).exposures[0].target— No vocabulary term exactly matches 'cervical sympathetic trunk / carotid sinus nerve region'; classified as other.exposures[1].timing.pulse_duration_ms— Pulse duration not explicitly stated for the human protocol, only duty cycle (50%) and pulse frequency (100 Hz).anaesthesia— Value reflects the rat experiments (conducted under isoflurane anaesthesia); human patients and healthy volunteers were conscious/not anaesthetised.