Mechanistic insight into spontaneous transition from cellular alternans to arrhythmia—A simulation study

Wang, Wei; Zhang, Shanzhuo; Ni, Haibo; Garratt, Clifford J.; Boyett, Mark R.; Hancox, Jules C.; Zhang, Henggui

doi:10.1371/journal.pcbi.1006594

Cited by 12 publications

(24 citation statements)

References 85 publications

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“…In the control simulation, the diffusion coefficient D was set to 0.167 mm 2 /ms to achieve a conduction velocity (CV) of approximately 0.60 m/s along the cable, which was in line with the CV previously used for tissue simulations [ 50 – 52 ]. The CV was calculated using the method in [ 53 ]. It has previously been reported that fibrosis may reduce the cell-to-cell coupling [ 39 ].…”

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%

Heart failure-induced atrial remodelling promotes electrical and conduction alternans

Zhao

Zhang

et al. 2020

PLoS Comput Biol

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“…The APD90 rate dependent curve and restitutions curve were calculated using the dynamic pacing protocol and the standard S1-S2 protocol respectively [12] to analyze the genesis of AP alternans under control and IKur block conditions. Firstly, the cell model was paced at 1000 ms for 100 beats to reach relatively steady state as initial values for next simulation under control and various IKur block conditions.…”

Section: Methodsmentioning

confidence: 99%

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

Zhao¹,

Li²,

Wang³

et al. 2019

2019 Computing in Cardiology Conference (CinC)

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The Kv1.5 channel-mediated, ultra-rapid delayed rectifier K + current (IKur) is a promising target for antiarrhythmic drugs due to its 'atrial-selective' property. However, it is unclear yet if blocking IKur can increase the alternans susceptibility in normal atria.This study aimed to investigate the effect of blocking IKur on the genesis of AP alternans associated with arrhythmogenesis. The updated canine atrial cell model developed by Ramirez et al. was used to implement the dynamic pacing protocol and the standard S1-S2 protocol to obtain rate dependent curves and restitution curves of AP duration (APD) and Ca 2+ transient which were further analyzed for the alternans susceptibility.Simulation results showed the prolonged AP and increased Ca 2+ transient (CaT) by blocking IKur. IKur block from 40% to 80% produced long-short-long-short APD and Ca 2+ transient alternans at pacing rate of ~ 2.3 Hz to 5 Hz. Further analysis showed that a possible mechanism for generating the observed alternans was due to the elevated plateau phase of AP by blocking IKur, which modulated APD and CaT via ICaL. Our findings demonstrate that blocking IKur may promote the genesis of APD and CaT alternans, implying a latent pro-arrhythmic effect in normal atria.

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“…For example, ejection fraction can be calculated based on the computed volume of the heart, which is an important indicator for diagnosing heart failure [2]. In addition, segmentation results can be utilized for reconstructing the 3D whole-heart model, which would be an excellent platform for investigating cardiac arrhythmia [3] and congenital cardiac diseases [4].…”

Section: Introductionmentioning

confidence: 99%

Improving Whole-Heart CT Image Segmentation by Attention Mechanism

Wang

Zhang

et al. 2020

IEEE Access

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Decent whole-heart segmentation from computed tomography (CT) can greatly contribute to the diagnosis and treatment of cardiovascular diseases. However, due to the difficulties such as blurred boundaries between neighbouring tissues and a large number of background voxels in medical images, automated whole-heart segmentation is still a challenging task. In this paper, we proposed three modified attention models, including simple negative example mining (SNEM), attention gate (AG) and U-CliqueNet (UCNet), to lead the deep learning network to focus on more salient information. These three attention modules were further implemented into a deeply-supervised 3D UNET separately and jointly, showing different degrees of improvement on the whole-heart segmentation task. Our experiments advised that SNEM was the most simple and effective attention mechanism for medical image processing among the three and the UCNet could reach the best performance. The combination of the attention mechanisms cannot always synergistically increase the accuracy, but joint models would have a positive influence in most cases. Finally, our network achieved a Dice score of 0.9112, which was a substantially higher performance than most of the state-of-the-art methods.

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Mechanistic insight into spontaneous transition from cellular alternans to arrhythmia—A simulation study

Cited by 12 publications

References 85 publications

Heart failure-induced atrial remodelling promotes electrical and conduction alternans

Heart failure-induced atrial remodelling promotes electrical and conduction alternans

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

Improving Whole-Heart CT Image Segmentation by Attention Mechanism

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