Anti ‐inflammatory Treatment with a Prodrug of Dexamethasone in Stellate Ganglia Attenuates Ventricular Arrhythmogenesis in Chronic Heart Failure Rats

Abstract

Cardiac sympathetic overactivation is a key trigger for ventricular arrhythmogenesis and is involved in sudden cardiac death in patients with chronic heart failure (CHF). Inflammatory infiltration in stellate ganglia (SG) has been considered as a critical factor to boost adrenergic activity in patients with ventricular arrhythmia. Our current study aims to investigate whether anti‐inflammatory treatment with a macromolecular prodrug of dexamethasone (P‐Dex) in the SG attenuates cardiac sympathetic overactivation and ventricular arrhythmogenesis in CHF rats. CHF rat was induced by surgical ligation of left coronary artery. P‐Dex (10 mM, 2 μl) was microinjected into bilateral SGs at 12 weeks after coronary artery ligation. Final experiments were performed at 9 days after P‐Dex treatment. ECG data obtained from 24‐hour continuous telemetry recording in conscious rats demonstrated that anti‐inflammatory treatment with P‐Dex in SGs reduced the incidence and duration of ventricular tachycardia/fibrillation (VT/VF). CHF‐induced heterogeneity of ventricular electrical activities was restored by P‐Dex treatment, as evidenced by P‐Dex‐shortened QT interval, QT dispersion as well as T‐peak to T‐end interval. In the power spectral analysis of heart rate variability, P‐Dex treatment in SGs normalized CHF‐increased ratio of low frequency to high frequency. In addition, anti‐inflammatory treatment with P‐Dex not only reduced CHF‐induced cardiac sympathetic nerve over‐activity, but also decreased the susceptibility to ventricular arrhythmias in CHF rats. Based on above data, we conclude that anti‐inflammatory treatment with P‐Dex in SGs attenuated CHF‐induced cardiac sympathetic overactivation and ventricular arrhythmia, suggesting that anti‐inflammatory treatment in SGs might be an effective therapeutic strategy to improve lethal ventricular arrhythmia and reduce mortality in patients with CHF.Support or Funding InformationThis study was supported by National Heart, Lung, and Blood Institute Grant (R01HL137832A to Y.‐L. Li)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.