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Low-intensity focused ultrasound modulation of the paraventricular nucleus to prevent myocardial infarction–induced ventricular arrhythmia

Chunrong Xiang, Ye Cheng, Xiaomei Yu, Tianlong Mao, Hao Luo, Haoyuan Hu, Yuzhe Wu, Ruiqi Sang, Zhuo Wang, Yujie Wang, Qinyu Luo, Jingyu Huang, Jiahui Zhao, Jiale Wang, Xinqi Wang, Mingxian Chen, Wei Liu, Liping Zhou, Songyun Wang, Hong Jiang

Heart Rhythm 2024, 21, 340-348 · 10.1016/j.hrthm.2023.11.026

rodentmyocardial infarctioninvasive electrophysiologyautonomic physiologyhistology molecular

Abstract

Background Our previous study showed that light-emitting diode modulation of the hypothalamic paraventricular nucleus (PVN), which is the control center of the sympathetic nervous system, might attenuate neuroinflammation in the PVN and prevent ventricular arrhythmias (VAs) after myocardial infarction (MI). Low-intensity focused ultrasound (LIFU) has deeper penetration than does light-emitting diode, while its effect on the PVN has not been reported. Objective This study aimed to explore the effect of LIFU modulation of the PVN on the inducibility of post-MI VAs. Methods Fifty-four Sprague-Dawley rats were randomly divided into acute control (n = 12, 22.22%), acute MI (AMI, n = 12, 22.22%), AMI + LIFU (n = 12, 22.22%), chronic control (n = 6, 11.11%), chronic MI (CMI, n = 6, 11.11%), and CMI + LIFU (n = 6, 11.11%) groups. MI was induced by left anterior artery ligation, and electrocardiographic recording for 0.5 hours after MI and programmed electrophysiological stimulation were used to test the vulnerability of VAs. Peripheral sympathetic neural activity was assessed by measuring left stellate ganglion neural activity. Finally, hearts and brains were extracted for Western blotting and histopathological analysis, respectively. Results Compared with the AMI group, AMI-induced VAs (P Conclusion LIFU modulation of the PVN may prevent the incidence of post-MI VAs by attenuating MI-induced sympathetic neural activation and inflammatory response.

Abstract via europepmc.

Speciesrat (Sprague-Dawley)
Subjects12, 6swept animals
Sessions per subjectnot reported
Randomisedyes
Blindingnot reported
Sham / controlnone
Auditory controlnot reported
Readout timingboth
Anaesthesiaanaesthetised
Readoutsinvasive electrophysiology, autonomic physiology, histology molecularLeft stellate ganglion (LSG) neural activity via microelectrode; ECG-based ventricular arrhythmia scoring and programmed electrophysiological stimulation; Western blot for IL-1b, TNF-a, IL-6; Iba-1 immunofluorescence (microglia); HE and TUNEL staining
Direction of effectinhibitoryLIFU stimulation of the PVN significantly decreased left stellate ganglion neural activity, reduced the inducibility of post-MI ventricular arrhythmias, and reduced microglial activation and myocardial inflammatory cytokine expression compared to MI without LIFU.
Adverse eventsnone observedHE and TUNEL immunofluorescence staining showed no obvious extravasation of red blood cells, abnormal cell morphology, inflammatory response, or increased apoptosis in the brain tissue of chronically LIFU-stimulated rats.

Exposures

Exposure 1: LIFU to the paraventricular nucleus (PVN)

Target: paraventricular nucleus — “hypothalamic paraventricular nucleus (PVN)
Device: other named manufacturer · Ultrasound Institute of Chongqing Medical University · GGT2007

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)1,000✓✓
Pulse duration (ms)not reportedimplied by duty cycle ÷ PRF: 0.5 ms (not stated by the paper)
Pulse repetition frequency (Hz)1,000✓✓
Duty cycle (%)50✓✓
Sonication duration (s)8✓✓
Pressure and intensity, by domain
Free-field pressure (kPa)not reported
Free-field Isppa (W/cm²)not reported
Free-field Ispta (W/cm²)not reported
In-situ estimatenot 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)2?
Protocol, in the paper’s words

LIFU at an intensity of 2.0 W/cm2, a frequency of 1 MHz, a pulse repetition frequency of 1 kHz, a duration of 8 seconds, and a duty cycle of 50% was administered to the skull surface corresponding to the PVN for 10 minutes in the acute MI (AMI) + LIFU group and 15 minutes every day in the chronic MI (CMI) + LIFU group.

Flags from extraction

  • n_subjectsPaper gives group sizes for acute (n=12) and chronic (n=6) LIFU-treated groups but no single stated total exposed to ultrasound; reported as a list
  • n_sessions_per_subjectAcute group received a single 10-minute LIFU session while chronic group received daily 15-minute sessions for 4 weeks (~28 sessions); no single value applies to both
  • exposures[0].unspecified_domain.isppa_w_cm2Paper reports a single 'intensity' value of 2.0 W/cm2 without specifying whether it is spatial-peak pulse-average (ISPPA) or spatial-peak temporal-average (ISPTA), and without stating measurement domain (free field vs in situ)
  • exposures[0].timing.pulse_duration_msPulse duration was not stated directly; computed from stated duty cycle (50%) and PRF (1 kHz) per the burst-duration rule