Vagus Nerve Stimulation by Focused Ultrasound Attenuates Acute Myocardial Ischemia/Reperfusion Injury Predominantly Through Cholinergic Anti-inflammatory Pathway
Qian Zhang, Qianyun Cai, Shenrong Zhong, Qin Li, Weibao Qiu, Juefei Wu
Cardiovascular Drugs and Therapy 2026, 40, 575-587 · 10.1007/s10557-025-07718-w
Abstract
Purpose This study investigates the cardioprotective effects of focused ultrasound stimulation (FUS) as a novel, noninvasive intervention for mitigating acute myocardial ischemia/reperfusion (I/R) injury. Methods In rat I/R models (30-min left anterior descending coronary artery (LAD) occlusion followed by 2-/24-h reperfusion), FUS was applied to the right cervical vagus nerve during early reperfusion (10-60 min post-reperfusion). The effects of FUS were assessed by analyzing inflammatory markers, arrhythmia incidence, pathological changes, echocardiographic parameters, pro-/anti-oxidative biomarkers, myocardial fibrosis, and infarct size. To elucidate the underlying mechanism, vagotomy and atropine administration were performed. Results FUS significantly reduced heart rate and inflammation in the 2-h reperfusion model. Compared to the I/R group, the I/R + FUS group exhibited markedly decreased premature ventricular contractions (221.00 ± 166.93 vs 83.11 ± 34.08, p Conclusion Targeted FUS neuromodulation exerts acute and sustained cardioprotection against I/R injury primarily through cholinergic anti-inflammatory mechanisms, offering a safer and more accessible alternative to traditional treatments.
Abstract via europepmc.
Exposures
Exposure 1: FUS of the right cervical vagus nerve
Target: vagus nerve — “right cervical vagus nerve (within the carotid sheath at the C5-C6 level)”
Device: custom-built · Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 1,710 | ✓✓✓ |
| Pulse duration (ms) | 10 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 10 | ✓✓✓⚑ |
| Duty cycle (%) | 10pulse duration × PRF gives 10% | ✓✓✓ |
| Sonication duration (s) | 360 | ✓✓✓⚑ |
| 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 | |
| Ispta, domain unspecified (W/cm²) | 0.0858 | ✓✓✓ |
Stimulation parameters were selected via a heart-rate-response optimisation sweep across frequency (0.5-5 MHz), amplitude (25-100%), continuous pulse duration T1 (0.2-10 ms), pulse-repetition period T2 (1-100 ms), stimulation duration T3 (0.2-360 s) and off-time. The combination of 1.71 MHz, 50% amplitude, T1=10 ms, T2=100 ms and T3=360 s produced >30% heart-rate reduction and was used for subsequent FUS experiments, in which FUS was applied to the right vagus nerve for 50 min beginning 10 min after reperfusion.
Flags from extraction
n_subjects— Paper states only per-group sizes (nine rats/group among 6 groups in part 1; 18 rats/group among 4 groups in part 2), never a total number of FUS-exposed animals; the group sizes of the FUS-treated arms (I/R+vagotomy+FUS, I/R+atropine+FUS, I/R+FUS = 9 each; I/R-24h+atropine+FUS, I/R-24h+FUS = 18 each) are listed rather than summed.exposures[0].timing.sonication_duration_s— T3=360 s is the stimulation-duration parameter identified during the frequency/amplitude optimisation sweep used to select final parameters; the therapeutic I/R protocol separately states FUS was applied for a total of 50 min after reperfusion, and the relationship between the 360 s parameter and this 50-min total exposure is not explained.exposures[0].timing.pulse_repetition_frequency_hz— PRF (10 Hz) is derived by converting the stated pulse-repetition period T2=100 ms to Hz, per the period-to-frequency unit-conversion rule (not an arithmetic combination of duty cycle and PRF).