Electro-mechanical dynamics of spiral waves in a discrete 2D model of human atrial tissue

Brocklehurst, Paul; Ni, Haibo; Zhang, Henggui; Ye, Jianqiao

doi:10.1371/journal.pone.0176607

Cited by 10 publications

(24 citation statements)

References 46 publications

(119 reference statements)

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“…Ni et al (2014) used an electromechanical model of the ventricles (Adeniran et al, 2013) to study the effect of KCNA5 mutation on the electromechanical function of the human atrial cell while Adeniran et al (2015) studied the effect of AF-induced electrical remodeling on the electromechanical function of the heart. Finally, a more recent study focused on the analysis of spiral waves when the atrial mechanoelectrical function is considered (Brocklehurst et al, 2017). In this study, one electrophysiological model of human atria (Colman et al, 2013) was modified to include the stretch-activated current, while combined with a mechanical model (Rice et al, 2008) which describes the active force generated in cellular level in response to the electrical signal.…”

Section: Resultsmentioning

confidence: 99%

Understanding the Beat-to-Beat Variations of P-Waves Morphologies in AF Patients During Sinus Rhythm: A Scoping Review of the Atrial Simulation Studies

et al. 2019

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The remarkable advances in high-performance computing and the resulting increase of the computational power have the potential to leverage computational cardiology toward improving our understanding of the pathophysiological mechanisms of arrhythmias, such as Atrial Fibrillation (AF). In AF, a complex interaction between various triggers and the atrial substrate is considered to be the leading cause of AF initiation and perpetuation. In electrocardiography (ECG), P-wave is supposed to reflect atrial depolarization. It has been found that even during sinus rhythm (SR), multiple P-wave morphologies are present in AF patients with a history of AF, suggesting a higher dispersion of the conduction route in this population. In this scoping review, we focused on the mechanisms which modify the electrical substrate of the atria in AF patients, while investigating the existence of computational models that simulate the propagation of the electrical signal through different routes. The adopted review methodology is based on a structured analytical framework which includes the extraction of the keywords based on an initial limited bibliographic search, the extensive literature search and finally the identification of relevant articles based on the reference list of the studies. The leading mechanisms identified were classified according to their scale, spanning from mechanisms in the cell, tissue or organ level, and the produced outputs. The computational modeling approaches for each of the factors that influence the initiation and the perpetuation of AF are presented here to provide a clear overview of the existing literature. Several levels of categorization were adopted while the studies which aim to translate their findings to ECG phenotyping are highlighted. The results denote the availability of multiple models, which are appropriate under specific conditions. However, the consideration of complex scenarios taking into account multiple spatiotemporal scales, personalization of electrophysiological and anatomical models and the reproducibility in terms of ECG phenotyping has only partially been tackled so far.

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Section: Resultsmentioning

confidence: 99%

Understanding the Beat-to-Beat Variations of P-Waves Morphologies in AF Patients During Sinus Rhythm: A Scoping Review of the Atrial Simulation Studies

et al. 2019

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“…The first 2D atrial model that incorporated mechano-electrical feedback was developed by Brocklehurst et alby strongly coupling the electrophysiological model of Colman et alto the mechanical myofilament model of Rice et al, with parameters modified based on experimental data. [86–88] A stretch-activated channel was incorporated into the model to simulate the mechano-electrical feedback. Satriano et aldeveloped a 3D implementation of a strongly coupled electromechanical atrial model using reconstructed images from a porcine heart and ex vivo experimental validation.…”

Section: Recent Advances In Atrial Modellingmentioning

confidence: 99%

Understanding AF Mechanisms Through Computational Modelling and Simulations

Aronis

Ali

Liang

et al. 2019

Arrhythm Electrophysiol Rev

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AF is a progressive disease of the atria, involving complex mechanisms related to its initiation, maintenance and progression. Computational modelling provides a framework for integration of experimental and clinical findings, and has emerged as an essential part of mechanistic research in AF. The authors summarise recent advancements in development of multi-scale AF models and focus on the mechanistic links between alternations in atrial structure and electrophysiology with AF. Key AF mechanisms that have been explored using atrial modelling are pulmonary vein ectopy; atrial fibrosis and fibrosis distribution; atrial wall thickness heterogeneity; atrial adipose tissue infiltration; development of repolarisation alternans; cardiac ion channel mutations; and atrial stretch with mechano-electrical feedback. They review modelling approaches that capture variability at the cohort level and provide cohort-specific mechanistic insights. The authors conclude with a summary of future perspectives, as envisioned for the contributions of atrial modelling in the mechanistic understanding of AF.

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“…Electromechanical models for human atrial cells simulating the electromechanical dynamics of the atrial myocytes were developed in our previous study [16]. Briefly, the Colman et al model of human atrial electrophysiology [7] was coupled to a modified Rice et al model of myofilament dynamics [17] and the stretch activated current (I SAC ) representing the effect of MEF, resulting in an electromechanical model capable of modelling the time courses of the AP and active force development of atrial myocytes.…”

Section: Modelling Electromechanical Dynamics Of Human Atrial Myocytesmentioning

confidence: 99%

“…A family of electromechanical models incorporating regional electrical heterogeneities in the present study was based on the Colman et al model of human atrial cells [7] and the Adeniran et al model of atrial electromechanics [16]. Although electromechanical models have been extensively developed for ventricles [13,15,[24][25][26][27], multi-scale models of atrial electromechanics is relatively rare [14].…”

Section: Relevance To Previous Studies and Clinical Relevancementioning

confidence: 99%

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In-silico investigations of the functional impact of KCNA5 mutations on atrial mechanical dynamics

Adeniran

Zhang

2017

Journal of Molecular and Cellular Cardiology

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A recent study has identified six novel genetic variations (D322H, E48G, A305T, D469E, Y155C, P488S) in KCNA5 (encoding Kv1.5 which carries the atrial-specific ultra-rapid delayed rectifier current, I) in patients with early onset of lone atrial fibrillation. These mutations are distinctive, resulting in either gain-of-function (D322H, E48G, A305T) or loss-of-function (D469E, Y155C, P488S) of I channels. Though affecting potassium channels, they may modulate the cellular active force and therefore atrial mechanical functions, which remains to be elucidated. The present study aimed to assess the inotropic effects of the identified six KCNA5 mutations on the human atria. Multiscale electromechanical models of the human atria were used to investigate the impact of the six KCNA5 mutations on atrial contractile functions. It was shown that the gain-of-function mutations reduced active contractile force primarily through decreasing the calcium transient (CaT) via a reduction in the L-type calcium current (I) as a secondary effect of modulated action potential, whereas the loss-of-function mutations mediated positive inotropic effects by increased CaT via enhancing the reverse mode of the Na/Ca exchanger. The 3D atrial electromechanical coupled model predicted different functional impacts of the KCN5A mutation variants on atrial mechanical contraction by either reducing or increasing atrial output, which is associated with the gain-of-function mutations or loss-of-function mutations in KCNA5, respectively. This study adds insights to the functional impact of KCNA5 mutations in modulating atrial contractile functions.

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Electro-mechanical dynamics of spiral waves in a discrete 2D model of human atrial tissue

Cited by 10 publications

References 46 publications

Understanding the Beat-to-Beat Variations of P-Waves Morphologies in AF Patients During Sinus Rhythm: A Scoping Review of the Atrial Simulation Studies

Understanding the Beat-to-Beat Variations of P-Waves Morphologies in AF Patients During Sinus Rhythm: A Scoping Review of the Atrial Simulation Studies

Understanding AF Mechanisms Through Computational Modelling and Simulations

In-silico investigations of the functional impact of KCNA5 mutations on atrial mechanical dynamics

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