Heart failure-induced atrial remodelling promotes electrical and conduction alternans

• DOI: 10.1371/journal.pcbi.1008048
• Publication Date: 2020-07-13T17:33:42Z
• Authors: Na Zhao; Qince Li; Kevin Zhang; Kuanquan Wang; Runnan He; Yongfeng Yuan; Henggui Zhang
• Keywords: Phospholamban; SERCA; Atrial action potential

Heart failure (HF) is associated with an increased propensity for atrial fibrillation (AF), causing higher mortality than AF or HF alone. It hypothesized that HF-induced remodelling of cellular and tissue properties promotes the genesis action potential (AP) alternans conduction perpetuate AF. However, mechanism underlying susceptibility to in remains incompletely elucidated. In this study, we investigated effects how electrophysiological (with prolonged AP duration) structural (reduced cell-to-cell coupling caused by fibrosis) can have effect on generation their at one-dimensional (1D) levels. Simulation results showed electrical duration, which was accompanied sarcoplasmic reticulum (SR) Ca2+ content transient amplitude. Further analysis demonstrated mainly due Ca2+-ATPase (SERCA) reuptake, modulated phospholamban (PLB) phosphorylation, decreased outward K+ current (Ito). The has been suggested SR did not fully recover previous levels end diastole, resulting a smaller release next beat. These produced alternans, further through Ca2+→AP AP→Ca2+ coupling, respectively. 1D model combined ion channel decrease fibrosis heart tissue's formation spatially discordant functional propagation dispersion, pro-arrhythmic. findings provide insights into arrhythmia association alternans.