1,705 research outputs found
Nonlinear physics of electrical wave propagation in the heart: a review
The beating of the heart is a synchronized contraction of muscle cells
(myocytes) that are triggered by a periodic sequence of electrical waves (action
potentials) originating in the sino-atrial node and propagating over the atria and
the ventricles. Cardiac arrhythmias like atrial and ventricular fibrillation (AF,VF)
or ventricular tachycardia (VT) are caused by disruptions and instabilities of these
electrical excitations, that lead to the emergence of rotating waves (VT) and turbulent
wave patterns (AF,VF). Numerous simulation and experimental studies during the
last 20 years have addressed these topics. In this review we focus on the nonlinear
dynamics of wave propagation in the heart with an emphasis on the theory of pulses,
spirals and scroll waves and their instabilities in excitable media and their application
to cardiac modeling. After an introduction into electrophysiological models for action
potential propagation, the modeling and analysis of spatiotemporal alternans, spiral
and scroll meandering, spiral breakup and scroll wave instabilities like negative line
tension and sproing are reviewed in depth and discussed with emphasis on their impact
in cardiac arrhythmias.Peer ReviewedPreprin
A note on stress-driven anisotropic diffusion and its role in active deformable media
We propose a new model to describe diffusion processes within active
deformable media. Our general theoretical framework is based on physical and
mathematical considerations, and it suggests to use diffusion tensors directly
coupled to mechanical stress. A proof-of-concept experiment and the proposed
generalised reaction-diffusion-mechanics model reveal that initially isotropic
and homogeneous diffusion tensors turn into inhomogeneous and anisotropic
quantities due to the intrinsic structure of the nonlinear coupling. We study
the physical properties leading to these effects, and investigate mathematical
conditions for its occurrence. Together, the experiment, the model, and the
numerical results obtained using a mixed-primal finite element method, clearly
support relevant consequences of stress-assisted diffusion into anisotropy
patterns, drifting, and conduction velocity of the resulting excitation waves.
Our findings also indicate the applicability of this novel approach in the
description of mechano-electrical feedback in actively deforming bio-materials
such as the heart
Competing mechanisms of stress-assisted diffusivity and stretch-activated currents in cardiac electromechanics
We numerically investigate the role of mechanical stress in modifying the
conductivity properties of the cardiac tissue and its impact in computational
models for cardiac electromechanics. We follow a theoretical framework recently
proposed in [Cherubini, Filippi, Gizzi, Ruiz-Baier, JTB 2017], in the context
of general reaction-diffusion-mechanics systems using multiphysics continuum
mechanics and finite elasticity. In the present study, the adapted models are
compared against preliminary experimental data of pig right ventricle
fluorescence optical mapping. These data contribute to the characterization of
the observed inhomogeneity and anisotropy properties that result from
mechanical deformation. Our novel approach simultaneously incorporates two
mechanisms for mechano-electric feedback (MEF): stretch-activated currents
(SAC) and stress-assisted diffusion (SAD); and we also identify their influence
into the nonlinear spatiotemporal dynamics. It is found that i) only specific
combinations of the two MEF effects allow proper conduction velocity
measurement; ii) expected heterogeneities and anisotropies are obtained via the
novel stress-assisted diffusion mechanisms; iii) spiral wave meandering and
drifting is highly mediated by the applied mechanical loading. We provide an
analysis of the intrinsic structure of the nonlinear coupling using
computational tests, conducted using a finite element method. In particular, we
compare static and dynamic deformation regimes in the onset of cardiac
arrhythmias and address other potential biomedical applications
Global alternans instability and its effect on non-linear wave propagation : dynamical Wenckebach block and self terminating spiral waves
The main mechanism of formation of reentrant cardiac arrhythmias is via formation of waveblocks at heterogeneities of cardiac tissue. We report that heterogeneity and the area of waveblock can extend itself in space and can result formation of new additional sources, or termination of existing sources of arrhythmias. This effect is based on a new form of instability, which we coin as global alternans instability (GAI). GAI is closely related to the so-called (discordant) alternans instability, however its onset is determined by the global properties of the APD-restitution curve and not by its slope. The APD-restitution curve relates the duration of the cardiac pulse (APD) to the time interval between the pulses, and can easily be measured in an experimental or even clinical setting. We formulate the conditions for the onset of GAI, study its manifestation in various 1D and 2D situations and discuss its importance for the onset of cardiac arrhythmias
Modeling the Heart as a Communication System
Electrical communication between cardiomyocytes can be perturbed during
arrhythmia, but these perturbations are not captured by conventional
electrocardiographic metrics. We developed a theoretical framework to quantify
electrical communication using information theory metrics in 2-dimensional cell
lattice models of cardiac excitation propagation. The time series generated by
each cell was coarse-grained to 1 when excited or 0 when resting. The Shannon
entropy for each cell was calculated from the time series during four
clinically important heart rhythms: normal heartbeat, anatomical reentry,
spiral reentry, and multiple reentry. We also used mutual information to
perform spatial profiling of communication during these cardiac arrhythmias. We
found that information sharing between cells was spatially heterogeneous. In
addition, cardiac arrhythmia significantly impacted information sharing within
the heart. Entropy localized the path of the drifting core of spiral reentry,
which could be an optimal target of therapeutic ablation. We conclude that
information theory metrics can quantitatively assess electrical communication
among cardiomyocytes. The traditional concept of the heart as a functional
syncytium sharing electrical information cannot predict altered entropy and
information sharing during complex arrhythmia. Information theory metrics may
find clinical application in the identification of rhythm-specific treatments
which are currently unmet by traditional electrocardiographic techniques.Comment: 26 pages (including Appendix), 6 figures, 8 videos (not uploaded due
to size limitation
Two dimensional electrophysiological characterization of human pluripotent stem cell-derived cardiomyocyte system.
Stem cell-derived cardiomyocytes provide a promising tool for human developmental biology, regenerative therapies, disease modeling, and drug discovery. As human pluripotent stem cell-derived cardiomyocytes remain functionally fetal-type, close monitoring of electrophysiological maturation is critical for their further application to biology and translation. However, to date, electrophysiological analyses of stem cell-derived cardiomyocytes has largely been limited by biologically undefined factors including 3D nature of embryoid body, sera from animals, and the feeder cells isolated from mouse. Large variability in the aforementioned systems leads to uncontrollable and irreproducible results, making conclusive studies difficult. In this report, a chemically-defined differentiation regimen and a monolayer cell culture technique was combined with multielectrode arrays for accurate, real-time, and flexible measurement of electrophysiological parameters in translation-ready human cardiomyocytes. Consistent with their natural counterpart, amplitude and dV/dtmax of field potential progressively increased during the course of maturation. Monolayer culture allowed for the identification of pacemaking cells using the multielectrode array platform and thereby the estimation of conduction velocity, which gradually increased during the differentiation of cardiomyocytes. Thus, the electrophysiological maturation of the human pluripotent stem cell-derived cardiomyocytes in our system recapitulates in vivo development. This system provides a versatile biological tool to analyze human heart development, disease mechanisms, and the efficacy/toxicity of chemicals
Nonlinear diffusion & thermo-electric coupling in a two-variable model of cardiac action potential
This work reports the results of the theoretical investigation of nonlinear
dynamics and spiral wave breakup in a generalized two-variable model of cardiac
action potential accounting for thermo-electric coupling and diffusion
nonlinearities. As customary in excitable media, the common Q10 and Moore
factors are used to describe thermo-electric feedback in a 10-degrees range.
Motivated by the porous nature of the cardiac tissue, in this study we also
propose a nonlinear Fickian flux formulated by Taylor expanding the voltage
dependent diffusion coefficient up to quadratic terms. A fine tuning of the
diffusive parameters is performed a priori to match the conduction velocity of
the equivalent cable model. The resulting combined effects are then studied by
numerically simulating different stimulation protocols on a one-dimensional
cable. Model features are compared in terms of action potential morphology,
restitution curves, frequency spectra and spatio-temporal phase differences.
Two-dimensional long-run simulations are finally performed to characterize
spiral breakup during sustained fibrillation at different thermal states.
Temperature and nonlinear diffusion effects are found to impact the
repolarization phase of the action potential wave with non-monotone patterns
and to increase the propensity of arrhythmogenesis
Negative tension of scroll wave filaments and turbulence in three-dimensional excitable media and application in cardiac dynamics
Scroll waves are vortices that occur in three-dimensional excitable media. Scroll waves have been observed in a variety of systems including cardiac tissue, where they are associated with cardiac arrhythmias. The disorganization of scroll waves into chaotic behavior is thought to be the mechanism of ventricular fibrillation, whose lethality is widely known. One possible mechanism for this process of scroll wave instability is negative filament tension. It was discovered in 1987 in a simple two variables model of an excitable medium. Since that time, negative filament tension of scroll waves and the resulting complex, often turbulent dynamics was studied in many generic models of excitable media as well as in physiologically realistic models of cardiac tissue. In this article, we review the work in this area from the first simulations in FitzHugh-Nagumo type models to recent studies involving detailed ionic models of cardiac tissue. We discuss the relation of negative filament tension and tissue excitability and the effects of discreteness in the tissue on the filament tension. Finally, we consider the application of the negative tension mechanism to computational cardiology, where it may be regarded as a fundamental mechanism that explains differences in the onset of arrhythmias in thin and thick tissue
Influence of cardiac tissue anisotropy on re-entrant activation in computational models of ventricular fibrillation
The aim of this study was to establish the role played by anisotropic diffusion in (i) the number of filaments and epicardial phase singularities that sustain ventricular fibrillation in the heart, (ii) the lifetimes of filaments and phase singularities, and (iii) the creation and annihilation dynamics of filaments and phase singularities. A simplified monodomain model of cardiac tissue was used, with membrane excitation described by a simplified 3-variable model. The model was configured so that a single re-entrant wave was unstable, and fragmented into multiple re-entrant waves. Re-entry was then initiated in tissue slabs with varying anisotropy ratio. The main findings of this computational study are: (i) anisotropy ratio influenced the number of filaments Sustaining simulated ventricular fibrillation, with more filaments present in simulations with smaller values of transverse diffusion coefficient, (ii) each re-entrant filament was associated with around 0.9 phase singularities on the surface of the slab geometry, (iii) phase singularities were longer lived than filaments, and (iv) the creation and annihilation of filaments and phase singularities were linear functions of the number of filaments and phase singularities, and these relationships were independent of the anisotropy ratio. This study underscores the important role played by tissue anisotropy in cardiac ventricular fibrillation
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