1,960 research outputs found
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
Virtual cardiac monolayers for electrical wave propagation
The complex structure of cardiac tissue is considered to be one of the main determinants of an arrhythmogenic substrate. This study is aimed at developing the first mathematical model to describe the formation of cardiac tissue, using a joint in silico-in vitro approach. First, we performed experiments under various conditions to carefully characterise the morphology of cardiac tissue in a culture of neonatal rat ventricular cells. We considered two cell types, namely, cardiomyocytes and fibroblasts. Next, we proposed a mathematical model, based on the Glazier-Graner-Hogeweg model, which is widely used in tissue growth studies. The resultant tissue morphology was coupled to the detailed electrophysiological Korhonen-Majumder model for neonatal rat ventricular cardiomyocytes, in order to study wave propagation. The simulated waves had the same anisotropy ratio and wavefront complexity as those in the experiment. Thus, we conclude that our approach allows us to reproduce the morphological and physiological properties of cardiac tissue
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
Filament behavior in a computational model of ventricular fibrillation in the canine heart
The aim of this paper was to quantify the behavior of filaments in a computational model of re-entrant ventricular fibrillation. We simulated cardiac activation in an anisotropic monodomain with excitation described by the Fenton-Karma model with Beeler-Reuter restitution, and geometry by the Auckland canine ventricle. We initiated re-entry in the left and right ventricular free walls, as well as the septum. The number of filaments increased during the first 1.5 s before reaching a plateau with a mean value of about 36 in each simulation. Most re-entrant filaments were between 10 and 20 mm long. The proportion of filaments touching the epicardial surface was 65%, but most of these were visible for much less than one period of re-entry. This paper shows that useful information about filament dynamics can be gleaned from models of fibrillation in complex geometries, and suggests that the interplay of filament creation and destruction may offer a target for antifibrillatory therap
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
Incorporating Inductances in Tissue-Scale Models of Cardiac Electrophysiology
In standard models of cardiac electrophysiology, including the bidomain and
monodomain models, local perturbations can propagate at infinite speed. We
address this unrealistic property by developing a hyperbolic bidomain model
that is based on a generalization of Ohm's law with a Cattaneo-type model for
the fluxes. Further, we obtain a hyperbolic monodomain model in the case that
the intracellular and extracellular conductivity tensors have the same
anisotropy ratio. In one spatial dimension, the hyperbolic monodomain model is
equivalent to a cable model that includes axial inductances, and the relaxation
times of the Cattaneo fluxes are strictly related to these inductances. A
purely linear analysis shows that the inductances are negligible, but models of
cardiac electrophysiology are highly nonlinear, and linear predictions may not
capture the fully nonlinear dynamics. In fact, contrary to the linear analysis,
we show that for simple nonlinear ionic models, an increase in conduction
velocity is obtained for small and moderate values of the relaxation time. A
similar behavior is also demonstrated with biophysically detailed ionic models.
Using the Fenton-Karma model along with a low-order finite element spatial
discretization, we numerically analyze differences between the standard
monodomain model and the hyperbolic monodomain model. In a simple benchmark
test, we show that the propagation of the action potential is strongly
influenced by the alignment of the fibers with respect to the mesh in both the
parabolic and hyperbolic models when using relatively coarse spatial
discretizations. Accurate predictions of the conduction velocity require
computational mesh spacings on the order of a single cardiac cell. We also
compare the two formulations in the case of spiral break up and atrial
fibrillation in an anatomically detailed model of the left atrium, and [...].Comment: 20 pages, 12 figure
Dispersion of cardiac action potential duration and the initiation of re-entry: A computational study
BACKGROUND:
The initiation of re-entrant cardiac arrhythmias is associated with increased dispersion of repolarisation, but the details are difficult to investigate either experimentally or clinically. We used a computational model of cardiac tissue to study systematically the association between action potential duration (APD) dispersion and susceptibility to re-entry.
METHODS:
We simulated a 60 Ă— 60 mm 2 D sheet of cardiac ventricular tissue using the Luo-Rudy phase 1 model, with maximal conductance of the K+ channel gKmax set to 0.004 mS mm-2. Within the central 40 Ă— 40 mm region we introduced square regions with prolonged APD by reducing gKmax to between 0.001 and 0.003 mS mm-2. We varied (i) the spatial scale of these regions, (ii) the magnitude of gKmax in these regions, and (iii) cell-to-cell coupling.
RESULTS:
Changing spatial scale from 5 to 20 mm increased APD dispersion from 49 to 102 ms, and the susceptible window from 31 to 86 ms. Decreasing gKmax in regions with prolonged APD from 0.003 to 0.001 mS mm-2 increased APD dispersion from 22 to 70 ms, and the susceptible window from <1 to 56 ms. Decreasing cell-to-cell coupling by changing the diffusion coefficient from 0.2 to 0.05 mm2 ms-1 increased APD dispersion from 57 to 88 ms, and increased the susceptible window from 41 to 74 ms.
CONCLUSION:
We found a close association between increased APD dispersion and susceptibility to re-entrant arrhythmias, when APD dispersion is increased by larger spatial scale of heterogeneity, greater electrophysiological heterogeneity, and weaker cell-to-cell coupling
Multiple mechanisms of spiral wave breakup in a model of cardiac electrical activity
It has become widely accepted that the most dangerous cardiac arrhythmias are
due to re- entrant waves, i.e., electrical wave(s) that re-circulate repeatedly
throughout the tissue at a higher frequency than the waves produced by the
heart's natural pacemaker (sinoatrial node). However, the complicated structure
of cardiac tissue, as well as the complex ionic currents in the cell, has made
it extremely difficult to pinpoint the detailed mechanisms of these
life-threatening reentrant arrhythmias. A simplified ionic model of the cardiac
action potential (AP), which can be fitted to a wide variety of experimentally
and numerically obtained mesoscopic characteristics of cardiac tissue such as
AP shape and restitution of AP duration and conduction velocity, is used to
explain many different mechanisms of spiral wave breakup which in principle can
occur in cardiac tissue. Some, but not all, of these mechanisms have been
observed before using other models; therefore, the purpose of this paper is to
demonstrate them using just one framework model and to explain the different
parameter regimes or physiological properties necessary for each mechanism
(such as high or low excitability, corresponding to normal or ischemic tissue,
spiral tip trajectory types, and tissue structures such as rotational
anisotropy and periodic boundary conditions). Each mechanism is compared with
data from other ionic models or experiments to illustrate that they are not
model-specific phenomena. The fact that many different breakup mechanisms exist
has important implications for antiarrhythmic drug design and for comparisons
of fibrillation experiments using different species, electromechanical
uncoupling drugs, and initiation protocols.Comment: 128 pages, 42 figures (29 color, 13 b&w
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