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Background Patients with rheumatoid arthritis are at twice the risk of ventricular arrhythmia and sudden cardiac death as the general population. We hypothesize that β-blocker treatment of rheumatoid arthritis is antiarrhythmic by producing synergistic anticatecholaminergic and anti-inflammatory effects. Methods and Results Collagen-induced arthritis (CIA) was induced in Lewis rats by immunization with type II collagen in Freund's incomplete adjuvant. The treatment with propranolol (4 mg/kg) started on the first day of immunization. We evaluated the ventricular vulnerability to ventricular arrhythmia using in vivo programmed stimulation and performed ex vivo optical mapping to measure the electrical remodeling of the heart. The ventricular tissue was further processed for immunohistochemical staining and protein array analysis. The assessment of ventricular vulnerability showed that the number and duration of the induced ventricular arrhythmia episodes were increased in CIA rats, which were improved with propranolol treatment. The sympathovagal index and the plasma level of catecholamines significantly increased in CIA rats, whereas the use of propranolol attenuated sympathetic hyperactivity. In the optical mapping study, electrical remodeling, characterized by prolonged action potential duration, slow conduction velocity, and steepened action-potential duration restitution, were noted in CIA rats and reversed in the propranolol-treatment group. The propranolol treatment was associated with decreases in paw thickness, fewer inflammatory cell infiltrations in the heart, reduced levels of cardiac inflammatory cytokines, and less cardiac fibrosis as compared with the CIA group. Conclusions CIA increased ventricular arrhythmia vulnerability through sympathetic hyperinnervation and proarrhythmic ventricular electrophysiological remodeling. Treatment with propranolol in CIA rats was both anti-inflammatory and antiarrhythmic.

背景

类风湿关节炎患者患室性心律失常和心源性猝死的风险是普通人群的两倍。我们假设β受体阻滞剂治疗类风湿关节炎具有协同的抗儿茶酚胺和抗炎作用，从而具有抗心律失常作用。

方法和结果

通过用弗氏不完全佐剂中的 II 型胶原免疫诱导 Lewis 大鼠产生胶原诱导性关节炎（CIA）。在免疫接种的第一天开始用普萘洛尔（4mg/kg）进行治疗。我们使用体内程控刺激评估心室易损性以诱发室性心律失常，并进行离体光学标测以测量心脏的电重构。进一步对心室组织进行免疫组织化学染色和蛋白质芯片分析。心室易损性评估显示 CIA 大鼠的诱发性室性心律失常发作的次数和持续时间增加，而普萘洛尔治疗可改善这些情况。CIA 大鼠的交感神经-迷走神经指数和儿茶酚胺的血浆水平显著增加，而普萘洛尔的使用则减弱了交感神经的过度活跃。在光学标测研究中，电重构表现为动作电位持续时间延长、传导速度减慢以及动作电位时程恢复斜率变陡，这些在 CIA 大鼠中都有出现，而在普萘洛尔治疗组中则得到了逆转。与 CIA 组相比，普萘洛尔治疗与爪厚度减小、心脏中炎性细胞浸润减少、心脏炎性细胞因子水平降低以及心脏纤维化减少相关。