Macrophage activation in stellate ganglia contributes to lung injury-induced arrhythmogenesis in male rats

Juan Hong, Ryan J. Adam, Lie Gao, Taija Hahka, Zhiqiu Xia, Dong Wang, Thomas A. Nicholas, Irving H. Zucker, Steven J. Lisco, Han Jun Wang

Research output: Contribution to journalArticlepeer-review

Abstract

Aim: Patients suffering from acute lung injury (ALI) are at high risk of developing cardiac arrhythmias. We hypothesized that stellate ganglia (SG) neural inflammation contributes to ALI-induced arrhythmia. Methods: We created an ALI rat model using a single tracheal instillation of bleomycin (2.5 mg/kg), with saline as a sham control. We recorded ECGs by implanted radiotelemetry in male bleomycin and sham rats treated with and without oral minocycline (20 mg/kg/d), an anti-inflammatory drug that inhibits microglia/macrophage activation. The SG neuronal excitability was assessed by electrophysiology experiments. Results: ECG data showed that bleomycin-exposed rats exhibited significantly more spontaneous premature ventricular contractions (PVCs) from 1- to 3-week post-induction compared with sham rats, which was mitigated by chronic oral administration of minocycline. The bleomycin-exposed rats displayed a robust increase in both the number of Iba1-positive macrophages and protein expression of interferon regulatory factor 8 in the SG starting as early at 1-week post-exposure and lasted for at least 4 weeks, which was largely attenuated by minocycline. Heart rate variability analysis indicated autonomic imbalance during the first 2-week post-bleomycin, which was significantly attenuated by minocycline. Electrical stimulation of the decentralized SG triggered more PVCs in bleomycin-exposed rats than sham and bleomycin + minocycline rats. Patch-clamp data demonstrated enhanced SG neuronal excitability in the bleomycin-exposed rats, which was attenuated by minocycline. Co-culture of lipopolysaccharide (LPS)-pretreated macrophages with normal SG neurons enhanced SG neuronal excitability. Conclusion: Macrophage activation in the SG contributes to arrhythmogenesis in bleomycin-induced ALI in male rats.

Original languageEnglish (US)
Article numbere13657
JournalActa Physiologica
Volume232
Issue number2
DOIs
StatePublished - Jun 2021

Keywords

  • acute lung injury
  • arrhythmogenesis
  • autonomic dysfunction
  • cardiopulmonary afferents
  • neural inflammation
  • sympatho-excitation

ASJC Scopus subject areas

  • Physiology

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