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Low-Intensity Ultrasound Modulation May Prevent Myocardial Infarction-induced Sympathetic Neural Activation and Ventricular Arrhythmia

Songyun Wang, Binxun Li, Xuemeng Li, Lin Wu, Tongjian Zhu, Dongdong Zhao, Hong Jiang

Journal of Cardiovascular Pharmacology 2020, 75, 432-438 · 10.1097/fjc.0000000000000810

large animalmyocardial infarctioninvasive electrophysiologyautonomic physiologyhistology molecular

Abstract

Background Low-intensity focused ultrasound (LIFU) has been shown to be a beneficial tool for autonomic nervous system modulation, but its effect on the left stellate ganglion (LSG) remains unknown. Objective To seek the effect of LIFU on myocardial infarction (MI)-induced LSG activation and ventricular arrhythmias (VAs). Methods In this study, 20 dogs were included and randomly divided into the LIFU (LIFU & MI, n = 8), Sham (sham LIFU & MI, n = 8), and Control group (sham LIFU & sham MI, n = 4). For each LIFU intervention (1.0-2.0 W, 10 minutes) of the LSG, the LSG function, ventricular effective refractory period (ERP), and temperature were tested pre-intervention and postintervention. Thereafter, MI was induced by left anterior artery ligation and VAs were recorded for 1 hour. At the end, both the LSG and the heart were extracted for biomedical and histological analysis. Results In the Sham group, no significant change was shown in ventricular ERP or LSG function for any intensity settings of sham LIFU intervention when compared with the group baseline. In the LIFU group, however, both 1.5 and 2.0 W LIFU modulation of LSG resulted in significant prolongation of ERP and attenuation of LSG function. Furthermore, the incidence of VAs was significantly attenuated in the LIFU group compared with the Sham group. Moreover, histological analysis showed that no damage or apoptosis was observed in LSG although a statistically significant increase was shown in temperature (maximal increase Conclusion LIFU stimulation may be a safe and beneficial tool for LSG attenuation and VA prevention in the MI canine model.

Abstract via europepmc.

Speciesdog
Subjects8 animals
Sessions per subject1
Randomisedyes
Blindingnot reported
Sham / controlundescribed
Auditory controlnot reported
Readout timingoffline
Anaesthesiaanaesthetised
Readoutsinvasive electrophysiology, autonomic physiology, histology molecular — ventricular effective refractory period; blood pressure response to LSG stimulation; ventricular arrhythmia incidence on ECG; H&E, TUNEL, c-fos western blot, IL-1b and IL-18 mRNA; thermocouple temperature
Direction of effectinhibitoryLIFU at 1.5 and 2.0 W attenuated left stellate ganglion function (smaller pressor response to LSG stimulation), prolonged ventricular ERP and reduced post-MI ventricular arrhythmias and LSG c-fos; 1.0 W and sham had no effect on LSG function.
Adverse eventsnone observedNo damage on H&E or increase in TUNEL staining in the LSG; temperature rose by at most 0.7 C (statistically significant at 1.5 and 2.0 W).

Exposures

Exposure 1: LIFU to left stellate ganglion (1.0, 1.5, 2.0 W)

Target: superior cervical ganglion — “left stellate ganglion (LSG)”
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)600✓✓✓⚑
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
Protocol, in the paper’s words

LIFU (frequency 1 MHz, pulse repetition frequency 1 KHz, duty cycle 8 seconds, and duty cycle % 50%) with intensities of 1.0, 1.5 and 2.0 W applied to the LSG for 10 minutes at each intensity, in increasing order, with ERP and LSG function measured before and after each.

Flags from extraction

  • exposures[0].timing.sonication_duration_s — Text states 'duty cycle 8 seconds' as well as 50 %, which is unexplained; 10 min per intensity is recorded as the sonication duration.
  • exposures[0].free_field — Intensity given only as electrical/acoustic power in W (1.0, 1.5, 2.0 W); no pressure or W/cm2.
  • exposures[0].timing.pulse_duration_ms — Not stated; not computed.
  • safety_notes — Abstract gives maximal temperature increase as garbled ',18C'; results text gives 0.7 C.
  • n_subjects — 20 dogs: LIFU+MI 8, sham LIFU+MI 8, sham LIFU+sham MI 4; only the 8 LIFU dogs received active ultrasound.
  • sham_type — Sham LIFU mechanism not described.