Atrial Fibrillation Promotion in a Rat Model of Rheumatoid Arthritis

Abstract

BackgroundThe prevalence of atrial fibrillation (AF) is significantly higher in rheumatoid arthritis (RA) patients, but the underlying mechanisms remain poorly understood. The goal of this study was to assess the effects of RA on AF susceptibility and atrial arrhythmogenic remodeling in a rat model of RA.Methods and ResultsCollagen‐induced arthritis was induced in rats by immunization with type II collagen in Freund's incomplete adjuvant. Among the rats that developed arthritis, AF susceptibility and atrial remodeling were examined 8 weeks after the primary immunization. AF inducibility and duration were substantially increased in collagen‐induced arthritis rats, and AF duration was significantly and positively correlated with the serum IL‐6 and TNF‐α levels. Rats with collagen‐induced arthritis showed prolonged atrial conduction time with no changes in the atrial effective refractory period. Atrial conduction delay was accompanied by significantly increased atrial fibrosis. In addition, atrial structural and autonomic remodeling, including left atrial dilation, apoptosis and autophagy of atrial myocytes, and atrial heterogeneous sympathetic hyperinnervation, was observed. Interestingly, we found that collagen‐induced arthritis had no significant effects on connexins, Nav1.5, and the main ion channels' protein expressions in atria.ConclusionsWe demonstrated that RA increased AF susceptibility by inducing AF‐promoting atrial remodeling. This study may provide insights into mechanisms underlying RA‐induced AF and validate a model that is suitable for further mechanistic and therapeutic exploration.

An implantable system for long-term assessment of atrial fibrillation substrate in unanesthetized rats exposed to underlying pathological conditions

“…In addition, as already described (Fig. 3), histological analysis did not reveal increased LA fibrosis in the sham group, as would be expected in rats exposed to systemic inflammation 31,32 .…”

“…This intriguing finding led us to several additional experiments in order to try to reveal possible source\s for this phenomenon. The results strongly argue against the involvement of systemic inflammation as an underlying mechanism based on direct serum measurements of inflammatory cytokines as well as the absence of atrial fibrosis which is expected to occur in the presence of systemic inflammation 31,32,46 . Post-operative AF due to the thoracotomy we performed in the implantation surgery is another option that should be considered.…”

Associations of inflammatory markers with impaired left ventricular diastolic and systolic function in collagen-induced arthritis

“…investigation [31]. The discrepancies may be explained by the onset, severity and duration of the different arthritic protocols used in the latter and current studies.…”

“…However, no changes in pulsed Doppler markers of diastolic function (E/A) were observed in CIA rats compared to controls. In contrast, one study showed impaired early diastolic filling velocity (E) in female CIA rats [31]. No other markers of diastolic function were assessed in the respective https://doi.org/10.1371/journal.pone.0230657.g005…”

Evidence for Inflammation as a Driver of Atrial Fibrillation

“…In many clinical studies, the prevalence of AF is shown to be increased in RA patients (43). In a collagen-induced arthritis rat model, RA can cause AF and increase AF duration (44), suggesting roles in the initiation and maintenance of the arrhythmia (41).…”