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Macrophage Activation in Stellate Ganglia Contributes to Lung Injury‐Induced Arrhythmogenesis in Male Rats

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Acta Physiologica

Published online on


["Acta Physiologica, Accepted Article. ", "\nAbstract\n\nAim\nPatients 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.\n\n\nMethods\nWe 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 radio‐telemetry in male bleomycin and sham rats treated with and without oral minocycline (20 mg/kg/day), an anti‐inflammatory drug that inhibits microglia/macrophage activation. The SG neuronal excitability was assessed by electrophysiology experiments.\n\n\nResults\nECG data showed that bleomycin‐exposed rats exhibited significantly more spontaneous premature ventricular contractions (PVCs) from one to three weeks post induction compared to 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 two weeks 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.\n\n\nConclusion\nMacrophage activation in the SG contributes to arrhythmogenesis in bleomycin‐induced ALI in male rats.\n\n"]