Abstract P2004: Neural Inflammation in Stellate Ganglia Mediates Lung Injury-Induced Arrhythmogenesis

Abstract

Background: People who suffer lung injury, incurred through a variety of means, are at greatly increased risk of developing cardiac arrhythmias. Treatment options remain limited. We propose that stellate ganglia neuro-inflammation contributes to lung injury-induced arrhythmogenesis. Methods: We created lung injury in adult Sprague-Dawley rats by a single tracheal instillation of Bleomycin (Bleo, 2.5 mg/kg), and used Saline instillation as a control. We recorded ECGs in conscience, freely moving Bleo and Saline rats treated with and without oral minocycline (20 mg/kg/day for 4 weeks, an anti-inflammatory drug to inhibit microglia/macrophage activation) using implantable radio-telemeters. During terminal experimentation we investigated the effect of minocycline on isolated electrical stellate stimulation-induced cardiac arrhythmias in Bleo rats. Results: Bleo rats exhibited lung lesions at necropsy and lung fibrosis histologically. Bleo rats, on average, had more premature ventricular contractions (PVCs) than Saline rats, an effect largely prevented by chronic treatment with minocycline. (PVC data 1-wk post Bleo: Saline 22±12, Bleo 481±394*#, Bleo+Mino 24±9. PVC data 2-wks post Bleo: Saline 6±2, Bleo 255±165*, Bleo+Mino 21±8. Data are AVG±SEM number of PVCs over 24-hr, n=5-6 for all groups. *P<0.05 between Bleo vs. Saline, #P<0.05 Bleo vs. Bleo+Mino). Isolated electrical stellate ganglia stimulation caused a frequency-dependent increase in heart rate without arrhythmias in normal rats but in Bleo rats triggered a significant number of PVCs, indicating stellate ganglia excitability post lung injury. This effect was greatly reduced in Bleo rats receiving minocycline. Since our isolated stellate preparation is decentralized, these data clearly suggest a local protective effect of minocycline on stellate ganglia in Bleo rats. Immunofluorescence data suggested that compared to sham-operated rats, the number of Iba-1-positive (a macrophage marker) cells in stellate ganglia of bleomycin-treated rats was significantly increased at 1 week post lung injury and lasted for at least 4 weeks. Conclusion: Our data showed that stellate ganglia neuroinflammation contributes to arrhythmogenesis in our Bleo lung injury rat model.