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

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

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

A parallel solver for reaction-diffusion systems in computational electrocardiology

In this work, a parallel three-dimensional solver for numerical simulations in computational electrocardiology is introduced and studied. The solver is based on the anisotropic Bidomain %(AB) cardiac model, consisting of a system of two degenerate parabolic reaction-diffusion equations describing the intra and extracellular potentials of the myocardial tissue. This model includes intramural fiber rotation and anisotropic conductivity coefficients that can be fully orthotropic or axially symmetric around the fiber direction. %In case of equal anisotropy ratio, this system reduces to The solver also includes the simpler anisotropic Monodomain model, consisting of only one reaction-diffusion equation. These cardiac models are coupled with a membrane model for the ionic currents, consisting of a system of ordinary differential equations that can vary from the simple FitzHugh-Nagumo (FHN) model to the more complex phase-I Luo-Rudy model (LR1). The solver employs structured isoparametric $Q_1$ finite elements in space and a semi-implicit adaptive method in time. Parallelization and portability are based on the PETSc parallel library. Large-scale computations with up to $O(10^7)$ unknowns have been run on parallel computers, simulating excitation and repolarization phenomena in three-dimensional domains

An HPC-Based Approach to Study Living System Computational Model Parameter Dependency

High performance computing (HPC) allows one to run in parallel large amount of independent numerical experiments for computationally intensive simulations of a complex system. Results of such experiments can be used to derive dependencies between functional characteristics of simulated system and parameters of the computational model. In this paper, we implemented this HPC approach with using a computational model of the electrical activity in the left ventricle of human heart. To illustrate possibilities of the approach, we analyzed dependencies of electrophysiological characteristics of the left ventricle on the parameters of its geometry. Particularly, we identified a dependence of the dynamics of activated myocardium part during excitation on the model parameters of the myocardial fiber orientation in the ventricular wall

A quasi-one-dimensional theory for anisotropic propagation of excitation in cardiac muscle

It has been shown that propagation of excitation in cardiac muscle is anisotropic. Compared to propagation at right angles to the long axes of the fibers, propagation along the long axis is faster, the extracellular action potential (AP) is larger in amplitude, and the intracellular AP has a lower maximum rate of depolarization, a larger time constant of the foot, and a lower peak amplitude. These observations are contrary to the predictions of classical one-dimensional (1-D) cable theory and, thus far, no satisfactory theory for them has been reported. As an alternative description of propagation in cardiac muscle, this study provides a quasi-1-D theory that includes a simplified description of the effects of action currents in extracellular space as well as resistive coupling between surface and deeper fibers in cardiac muscle. In terms of classical 1-D theory, this quasi-1-D theory reveals that the anisotropies in the wave form of the AP arise from modifications in the effective membrane ionic current and capacitance. The theory also shows that it is propagation in the longitudinal, not in the transverse direction that deviates from classical 1-D cable theory

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

A modeling framework for contact, adhesion and mechano-transduction between excitable deformable cells

Cardiac myocytes are the fundamental cells composing the heart muscle. The propagation of electric signals and chemical quantities through them is responsible for their nonlinear contraction and dilatation. In this study, a theoretical model and a finite element formulation are proposed for the simulation of adhesive contact interactions between myocytes across the so-called gap junctions. A multi-field interface constitutive law is proposed for their description, integrating the adhesive and contact mechanical response with their electrophysiological behavior. From the computational point of view, the initial and boundary value problem is formulated as a structure-structure interaction problem, which leads to a straightforward implementation amenable for parallel computations. Numerical tests are conducted on different couples of myocytes, characterized by different shapes related to their stages of growth, capturing the experimental response. The proposed framework is expected to have impact on the understanding how imperfect mechano-transduction could lead to emergent pathological responses.Comment: 31 pages, 17 figure