Cardiac sympathetic overactivation is involved in arrhythmogenesis in patients with chronic heart failure (CHF). Inflammatory infiltration in the stellate ganglion (SG) is a critical factor for cardiac sympathoexcitation in patients with ventricular arrhythmias. This study aims to investigate if macrophage depletion in SGs decreases cardiac sympathetic overactivation and ventricular arrhythmogenesis in CHF. Surgical ligation of the coronary artery was used for induction of CHF. Clodronate liposomes were microinjected into bilateral SGs of CHF rats for macrophage depletion. Using cytokine array, immunofluorescence staining, and Western blot analysis, we found that macrophage expansion and expression of TNFα and IL-1β in SGs were markedly increased in CHF rats. Flow cytometry data confirmed that the percentage of macrophages in SGs was higher in CHF rats than that in sham rats. Clodronate liposomes significantly reduced CHF-elevated proinflammatory cytokine levels and macrophage expansion in SGs. Clodronate liposomes also reduced CHF-increased N-type Ca²⁺ currents and excitability of cardiac sympathetic postganglionic neurons and inhibited CHF-enhanced cardiac sympathetic nerve activity. ECG data from 24-h, continuous telemetry recording in conscious rats demonstrated that clodronate liposomes not only restored CHF-induced heterogeneity of ventricular electrical activities, but also decreased the incidence and duration of ventricular tachycardia/fibrillation in CHF. Macrophage depletion with clodronate liposomes attenuated CHF-induced cardiac sympathetic overactivation and ventricular arrhythmias through reduction of macrophage expansion and neuroinflammation in SGs.

心脏交感神经过度激活与慢性心力衰竭 (CHF) 患者的心律失常发生有关。星状神经节 (SG) 的炎症浸润是室性心律失常患者心脏交感神经兴奋的关键因素。本研究旨在调查 SGs 中巨噬细胞耗竭是否会降低 CHF 中的心脏交感神经过度激活和室性心律失常发生。冠状动脉的外科结扎用于诱导CHF。将氯膦酸盐脂质体显微注射到 CHF 大鼠的双侧 SGs 中以消耗巨噬细胞。使用细胞因子阵列、免疫荧光染色和蛋白质印迹分析，我们发现 CHF 大鼠的 SGs 中巨噬细胞扩增和 TNFα 和 IL-1β 的表达显着增加。流式细胞仪数据证实，CHF 大鼠 SGs 中巨噬细胞的百分比高于假手术大鼠。氯膦酸盐脂质体显着降低了 SG 中 CHF 升高的促炎细胞因子水平和巨噬细胞扩增。氯膦酸盐脂质体还降低了 CHF 增加的 N 型 Ca^{心脏交感神经节后神经元的2+}电流和兴奋性，并抑制 CHF 增强的心脏交感神经活动。来自有意识大鼠的 24 小时连续遥测记录的 ECG 数据表明，氯膦酸盐脂质体不仅恢复了 CHF 引起的心室电活动的异质性，而且降低了 CHF 中室性心动过速/纤颤的发生率和持续时间。用氯膦酸盐脂质体消耗巨噬细胞可通过减少 SG 中的巨噬细胞扩张和神经炎症来减轻 CHF 诱导的心脏交感神经过度激活和室性心律失常。