Anti‐Inflammatory and Antiarrhythmic Effects of Beta Blocker in a Rat Model of Rheumatoid Arthritis

Abstract

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.