An integrative appraisal of mechano-electric feedback mechanisms in the heart
Viviane Timmermann,Lars A. Dejgaard,Kristina H. Haugaa,Andrew G. Edwards,Andrew G. Edwards,Joakim Sundnes,Joakim Sundnes,Andrew D. McCulloch,Samuel T. Wall +8 more
TLDR
These model results suggest that known mechanisms of mechano-electric coupling in cardiac myocyte may be sufficient to be pro-arrhythmic, but only in combination and under specific strain patterns.Abstract:
Mechanically-induced alterations in cardiac electrophysiology are referred to as mechano-electric feedback (MEF), and play an important role in electrical regulation of cardiac performance. The influence of mechanical stress and strain on electrophysiology has been investigated at all levels, however the role of MEF in arrhythmia remains poorly understood. During the normal contraction of the heart, mechano-sensitive processes are an implicit component of cardiac activity. Under abnormal mechanical events, stretch-activated mechanisms may contribute to local or global changes in electrophysiology (EP). While such mechanisms have been hypothesised to be involved in mechanically-initiated arrhythmias, the details of these mechanisms and their importance remain elusive.
We assess the theoretical role of stretch mechanisms using coupled models of cellular electrophysiology and sarcomere contraction dynamics. Using models of single ventricular myocytes, we first investigated the potential MEF contributions of stretch-activated currents (SAC), and stretch-induced myofilament calcium release, to test how strain and fibrosis may alter cellular electrophysiology. For all models investigated, SACs were alone not sufficient to create a pro-arrhythmic perturbation of the action potential with stretch. However, when combined with stretch-induced myofilament calcium release, the action potential could be shortened depending on the timing of the strain. This effect was highly model dependent, with a canine epicardial EP model being the most sensitive.
These model results suggest that known mechanisms of mechano-electric coupling in cardiac myocyte may be sufficient to be pro-arrhythmic, but only in combination and under specific strain patterns.read more
Citations
More filters
Journal ArticleDOI
Cardiac Mechano-Electric Coupling: Acute Effects of Mechanical Stimulation on Heart Rate and Rhythm
T. Alexander Quinn,Peter Kohl +1 more
TL;DR: The power of computational modelling is demonstrated in developing a more comprehensive understanding of 'what makes the heart tick' and the implications of MEC in health and disease in human are presented.
Journal ArticleDOI
Cardiomyocyte calcium handling in health and disease : Insights from in vitro and in silico studies
TL;DR: The fundamental mechanisms of cardiomyocyte Ca2+ handling in health and disease are described, an overview of currently available computational models forCardiomyocytes Ca2-handling handling is provided, and important uncertainties and open questions about cardo- cardiac arrhythmias are discussed.
Journal ArticleDOI
In-silico human electro-mechanical ventricular modelling and simulation for drug-induced pro-arrhythmia and inotropic risk assessment.
Francesca Margara,Zhinuo J. Wang,Francesc Levrero-Florencio,Alfonso Santiago,Mariano Vázquez,Alfonso Bueno-Orovio,Blanca Rodriguez +6 more
TL;DR: The human calibrated and evaluated modelling and simulation framework constructed in this study opens new avenues for future investigations into the complex interplay between the electrical and mechanical cardiac substrates, its modulation by pharmacological action, and its translation to tissue and organ models of cardiac patho-physiology.
Journal ArticleDOI
Competing Mechanisms of Stress-Assisted Diffusivity and Stretch-Activated Currents in Cardiac Electromechanics.
Alessandro Loppini,Alessio Gizzi,Ricardo Ruiz-Baier,Christian Cherubini,Flavio H. Fenton,Simonetta Filippi +5 more
TL;DR: In this paper, the authors numerically investigate the role of mechanical stress in modifying the conductivity properties of cardiac tissue, and assess the impact of these effects in the solutions generated by computational models for cardiac electromechanics.
Journal ArticleDOI
Mechano-calcium and mechano-electric feedbacks in the human cardiomyocyte analyzed in a mathematical model
Nathalie Balakina-Vikulova,Nathalie Balakina-Vikulova,Alexander V. Panfilov,Alexander V. Panfilov,Olga Solovyova,Olga Solovyova,Leonid B. Katsnelson,Leonid B. Katsnelson +7 more
TL;DR: A novel model to describe electromechanical coupling and mechano-electric feedbacks in the human cardiomyocyte is developed that combines the ‘ten Tusscher–Panfilov’ electrophysiological model and the module of myocardium mechanical activity taken from the ’Ekaterinburg–Oxford’ model and adjusted to human data.
References
More filters
Journal ArticleDOI
A model for human ventricular tissue
TL;DR: A mathematical model of the action potential of human ventricular cells that, while including a high level of electrophysiological detail, is computationally cost-effective enough to be applied in large-scale spatial simulations for the study of reentrant arrhythmias.
Journal ArticleDOI
Atrial fibrosis: mechanisms and clinical relevance in atrial fibrillation.
Brett Burstein,Stanley Nattel +1 more
TL;DR: The current understanding of how atrial fibrosis creates a substrate for AF is reviewed, what is known about the mechanisms underlying fibrosis and its progression is summarized, and emerging therapeutic approaches aimed at attenuating structural remodeling to prevent AF are highlighted.
Journal ArticleDOI
Alternans and spiral breakup in a human ventricular tissue model.
TL;DR: A new version of the human ventricular cell model is developed, which is based on recent experimental measurements of human APD restitution and includes a more extensive description of intracellular calcium dynamics, which concludes that steepAPD restitution-mediated instability is a potential mechanism for VF in the human heart.
Journal ArticleDOI
Simulation of the Undiseased Human Cardiac Ventricular Action Potential: Model Formulation and Experimental Validation
TL;DR: A model for the undiseased human ventricular action potential (AP) which reproduces a broad range of physiological behaviors is developed and experiments for rate dependence of Ca2+ (including peak and decay) and intracellular sodium ([Na+]i) in undISEased human myocytes were quantitatively reproduced by the model.
Journal ArticleDOI
Structural and functional characterisation of cardiac fibroblasts
TL;DR: This review summarizes the understanding of fibroblast origin and identity, their structural organization and role in myocardial architecture, as well as functional aspects related to cell signalling and electro-mechanical function in the heart.