Effect of Blocking IKur on the Genesis of Action Potential Alternans in Canine Atrium

Zhao, Naiqin; Li, Qince; Wang, Kuanquan; Rui, Hebing; Yuan, Ye; Zhang, Henggui

doi:10.22489/cinc.2019.124

Cited by 1 publication

(1 citation statement)

References 12 publications

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“…At the single cell level, the dynamic pacing and standard S1-S2 protocols [ 53 , 54 ] were used to analyse the genesis of atrial alternans such as APD 90 alternans and the intracellular CaT alternans (including the amplitude and decay time), as previously described in detail [ 55 ]. The rate dependent curves of APD 90 , CaT amplitude, and CaT decay time against various pacing cycle lengths (PCLs) were obtained by applying a dynamic pacing protocol.…”

Section: Methodsmentioning

confidence: 99%

Heart failure-induced atrial remodelling promotes electrical and conduction alternans

Zhao

Zhang

et al. 2020

PLoS Comput Biol

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Heart failure (HF) is associated with an increased propensity for atrial fibrillation (AF), causing higher mortality than AF or HF alone. It is hypothesized that HF-induced remodelling of atrial cellular and tissue properties promotes the genesis of atrial action potential (AP) alternans and conduction alternans that perpetuate AF. However, the mechanism underlying the increased susceptibility to atrial alternans in HF remains incompletely elucidated. In this study, we investigated the effects of how HF-induced atrial cellular electrophysiological (with prolonged AP duration) and tissue structural (reduced cell-to-cell coupling caused by atrial fibrosis) remodelling can have an effect on the generation of atrial AP alternans and their conduction at the cellular and one-dimensional (1D) tissue levels. Simulation results showed that HF-induced atrial electrical remodelling prolonged AP duration, which was accompanied by an increased sarcoplasmic reticulum (SR) Ca 2+ content and Ca 2+ transient amplitude. Further analysis demonstrated that HF-induced atrial electrical remodelling increased susceptibility to atrial alternans mainly due to the increased sarcoplasmic reticulum Ca 2+ -ATPase (SERCA) Ca 2+ reuptake, modulated by increased phospholamban (PLB) phosphorylation, and the decreased transient outward K + current ( I to ). The underlying mechanism has been suggested that the increased SR Ca 2+ content and prolonged AP did not fully recover to their previous levels at the end of diastole, resulting in a smaller SR Ca 2+ release and AP in the next beat. These produced Ca 2+ transient alternans and AP alternans, and further caused AP alternans and Ca 2+ transient alternans through Ca 2+ →AP coupling and AP→Ca 2+ coupling, respectively. Simulation of a 1D tissue model showed that the combined action of HF-induced ion channel remodelling and a decrease in cell-to-cell coupling due to fibrosis increased the heart tissue’s susceptibility to the formation of spatially discordant alternans, resulting in an increased functional AP propagation dispersion, which is pro-arrhythmic. These findings provide insights into how HF promotes atrial arrhythmia in association with atrial alternans.

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Section: Methodsmentioning

confidence: 99%