Computational rabbit models to investigate the initiation, perpetuation, and termination of ventricular arrhythmia

Arevalo, Hermenegild; Boyle, Patrick; Trayanova, Natalia A.

doi:10.1016/j.pbiomolbio.2016.06.004

Cited by 13 publications

(8 citation statements)

References 124 publications

(153 reference statements)

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“…Ischemic heart disease remains the leading cause of death in the United States and globally 1,2 . In its most severe presentation, acute plaque rupture can occur that restricts blood flow to the myocardium causing myocardial infarction (MI), or cardiac muscle damage.…”

Section: Introductionmentioning

confidence: 99%

A comprehensive, multiscale framework for evaluation of arrhythmias arising from cell therapy in the whole post-myocardial infarcted heart

Franceschi

Huang

et al. 2019

Sci Rep

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Direct remuscularization approaches to cell-based heart repair seek to restore ventricular contractility following myocardial infarction (MI) by introducing new cardiomyocytes (CMs) to replace lost or injured ones. However, despite promising improvements in cardiac function, high incidences of ventricular arrhythmias have been observed in animal models of MI injected with pluripotent stem cell-derived cardiomyocytes (PSC-CMs). The mechanisms of arrhythmogenesis remain unclear. Here, we present a comprehensive framework for computational modeling of direct remuscularization approaches to cell therapy. Our multiscale 3D whole-heart modeling framework integrates realistic representations of cell delivery and transdifferentiation therapy modalities as well as representation of spatial distributions of engrafted cells, enabling simulation of clinical therapy and the prediction of emergent electrophysiological behavior and arrhythmogenensis. We employ this framework to explore how varying parameters of cell delivery and transdifferentiation could result in three mechanisms of arrhythmogenesis: focal ectopy, heart block, and reentry.

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Section: Introductionmentioning

confidence: 99%

A comprehensive, multiscale framework for evaluation of arrhythmias arising from cell therapy in the whole post-myocardial infarcted heart

Franceschi

Huang

et al. 2019

Sci Rep

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“…Please see also related communications in this issue by Arevalo et al. (2016) and Rog-Zielinska et al.…”

Section: Editors’ Notementioning

confidence: 97%

Rabbit-specific computational modelling of ventricular cell electrophysiology: Using populations of models to explore variability in the response to ischemia

Gemmell

Burrage

Rodríguez

et al. 2016

Progress in Biophysics and Molecular Biology

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Computational modelling, combined with experimental investigations, is a powerful method for investigating complex cardiac electrophysiological behaviour. The use of rabbit-specific models, due to the similarities of cardiac electrophysiology in this species with human, is especially prevalent. In this paper, we first briefly review rabbit-specific computational modelling of ventricular cell electrophysiology, multi-cellular simulations including cellular heterogeneity, and acute ischemia. This mini-review is followed by an original computational investigation of variability in the electrophysiological response of two experimentally-calibrated populations of rabbit-specific ventricular myocyte action potential models to acute ischemia. We performed a systematic exploration of the response of the model populations to varying degrees of ischemia and individual ischemic parameters, to investigate their individual and combined effects on action potential duration and refractoriness. This revealed complex interactions between model population variability and ischemic factors, which combined to enhance variability during ischemia. This represents an important step towards an improved understanding of the role that physiological variability may play in electrophysiological alterations during acute ischemia.

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“…Rabbit heart has much smaller size compared to human heart, so using this model can evidently reduce the computational complexity, significantly shortening the simulation time. In addition, the structure and electrophysiological characteristics of the human and rabbit heart have a high degree of similarity, making this model reliable [ 19 ].…”

Section: Background and Objectivementioning

confidence: 99%

Effect of ventricular myocardium characteristics on the defibrillation threshold

Wang

Jin

et al. 2018

THC

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Myocardium characteristics differ markedly among individuals and play an important role in defibrillation threshold. The accuracy of simulation models used in most published studies are still have room to be improved and most of them only discussed the effect of myocardial anisotropy on defibrillation threshold. In our manuscript, a rabbit ventricular finite-element (FE) volume conductor model with high precision was constructed. Ventricular myocardium characteristics include cardiomyocyte coupling and the degree of myocardial anisotropy, which are represented as the value and the ratio of anisotropic conductivity, respectively. Quantitative analysis was performed simultaneously in terms of cardiomyocyte coupling and the degree of myocardial anisotropy. Based on this, the combined effects of these two factors were further discussed. The electric field distributions of shocks and the defibrillation thresholds under different myocardial characteristics were simulated on this model. The simulation results revealed that as the degree of myocardial anisotropy increases, defibrillation threshold increases, and cardiomyocyte decoupling (decrease in electrical conductivity) can considerably increase the defibrillation threshold.

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Computational rabbit models to investigate the initiation, perpetuation, and termination of ventricular arrhythmia

Cited by 13 publications

References 124 publications

A comprehensive, multiscale framework for evaluation of arrhythmias arising from cell therapy in the whole post-myocardial infarcted heart

A comprehensive, multiscale framework for evaluation of arrhythmias arising from cell therapy in the whole post-myocardial infarcted heart

Rabbit-specific computational modelling of ventricular cell electrophysiology: Using populations of models to explore variability in the response to ischemia

Effect of ventricular myocardium characteristics on the defibrillation threshold

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