Key result
IL-6 neutralization significantly reduced the duration and probability of induced atrial fibrillation (P < 0.001) in sterile pericarditis rats by reversing Ca2+ handling abnormalities.
Why the study?
Pre-existing Ca2+ handling abnormalities form the arrhythmogenic substrate in postoperative AF, and whether IL-6-mediated Ca2+ handling abnormalities contribute to AF in sterile pericarditis rats was unknown.
Does IL-6 neutralization with an anti-IL-6 antibody reduce atrial fibrillation susceptibility and Ca2+ handling abnormalities in a sterile pericarditis rat model?
Does IL-6 neutralization with an anti-IL-6 antibody reduce atrial fibrillation susceptibility and Ca2+ handling abnormalities in a sterile pericarditis rat model?
p-value: p=<0.001
IL-6 neutralization reduces atrial fibrillation susceptibility in a rat model of sterile pericarditis by reversing Ca2+ handling abnormalities, suggesting a potential mechanism and therapeutic target for postoperative atrial fibrillation.
IL-6 neutralization merits investigation in inflammatory AF; hypothesis-generating and should not yet change practice.
Pre-existing Ca 2+ handling abnormalities constitute the arrhythmogenic substrate in patients developing postoperative atrial fibrillation (POAF), a common complication after cardiac surgery. Postoperative interleukin (IL)-6 levels are associated with atrial fibrosis in several animal models of POAF, contributing to atrial arrhythmias. Here, we hypothesize that IL-6-mediated-Ca 2+ handling abnormalities contribute to atrial fibrillation (AF) in sterile pericarditis (SP) rats, an animal model of POAF. SP was induced in rats by dusting atria with sterile talcum powder. Anti-rat-IL-6 antibody (16.7 μg/kg) was administered intraperitoneally at 30 min after the recovery of anesthesia. In vivo electrophysiology, ex vivo optical mapping, western blots, and immunohistochemistry were performed to elucidate mechanisms of AF susceptibility. IL-6 neutralization ameliorated atrial inflammation and fibrosis, as well as AF susceptibility in vivo and the frequency of atrial ectopy and AF with a reentrant pattern in SP rats ex vivo . IL-6 neutralization reversed the prolongation and regional heterogeneity of Ca 2+ transient duration, relieved alternans, reduced the incidence of discordant alternans, and prevented the reduction and regional heterogeneity of the recovery ratio of Ca 2+ transient. In agreement, western blots showed that IL-6 neutralization reversed the reduction in the expression of ryanodine receptor 2 (RyR2) and phosphorylated phospholamban. Acute IL-6 administration to isolated rat hearts recapitulated partial Ca 2+ handling phenotype in SP rats. In addition, intraperitoneal IL-6 administration to rats increased AF susceptibility, independent of fibrosis. Our results reveal that IL-6-mediated-Ca 2+ handling abnormalities in SP rats, especially RyR2-dysfunction, independent of IL-6-induced-fibrosis, early contribute to the development of POAF by increasing propensity for arrhythmogenic alternans.
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Liao et al. (2021) studied Atrial Fibrillation in Sterile Pericarditis (Animal Model). Anti-rat-IL-6 antibody vs. Normal goat IgG or Sham was evaluated on Probability and duration of induced atrial fibrillation (p=<0.001). IL-6 neutralization significantly reduced the duration and probability of induced atrial fibrillation (P < 0.001) in sterile pericarditis rats by reversing Ca2+ handling abnormalities.
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