8,333 research outputs found
Modelling the effect of gap junctions on tissue-level cardiac electrophysiology
When modelling tissue-level cardiac electrophysiology, continuum
approximations to the discrete cell-level equations are used to maintain
computational tractability. One of the most commonly used models is represented
by the bidomain equations, the derivation of which relies on a homogenisation
technique to construct a suitable approximation to the discrete model. This
derivation does not explicitly account for the presence of gap junctions
connecting one cell to another. It has been seen experimentally [Rohr,
Cardiovasc. Res. 2004] that these gap junctions have a marked effect on the
propagation of the action potential, specifically as the upstroke of the wave
passes through the gap junction.
In this paper we explicitly include gap junctions in a both a 2D discrete
model of cardiac electrophysiology, and the corresponding continuum model, on a
simplified cell geometry. Using these models we compare the results of
simulations using both continuum and discrete systems. We see that the form of
the action potential as it passes through gap junctions cannot be replicated
using a continuum model, and that the underlying propagation speed of the
action potential ceases to match up between models when gap junctions are
introduced. In addition, the results of the discrete simulations match the
characteristics of those shown in Rohr 2004. From this, we suggest that a
hybrid model -- a discrete system following the upstroke of the action
potential, and a continuum system elsewhere -- may give a more accurate
description of cardiac electrophysiology.Comment: In Proceedings HSB 2012, arXiv:1208.315
Rush-Larsen time-stepping methods of high order for stiff problems in cardiac electrophysiology
To address the issues of stability and accuracy for reaction-diffusion
equations, the development of high order and stable time-stepping methods is
necessary. This is particularly true in the context of cardiac
electrophysiology, where reaction-diffusion equations are coupled with stiff
ODE systems. Many research have been led in that way in the past 15 years
concerning implicit-explicit methods and exponential integrators. In 2009,
Perego and Veneziani proposed an innovative time-stepping method of order 2. In
this paper we present the extension of this method to the orders 3 and 4 and
introduce the Rush-Larsen schemes of order k (shortly denoted RL\_k). The RL\_k
schemes are explicit multistep exponential integrators. They display a simple
general formulation and an easy implementation. The RL\_k schemes are shown to
be stable under perturbation and convergent of order k. Their Dahlquist
stability analysis is performed. They have a very large stability domain
provided that the stabilizer associated with the method captures well enough
the stiff modes of the problem. The RL\_k method is numerically studied as
applied to the membrane equation in cardiac electrophysiology. The RL k schemes
are shown to be stable under perturbation and convergent oforder k. Their
Dahlquist stability analysis is performed. They have a very large stability
domain provided that the stabilizer associated with the method captures well
enough the stiff modes of the problem. The RL k method is numerically studied
as applied to the membrane equation in cardiac electrophysiology
Na/K pump regulation of cardiac repolarization: Insights from a systems biology approach
The sodium-potassium pump is widely recognized as the principal mechanism for active ion transport across the cellular membrane of cardiac tissue, being responsible for the creation and maintenance of the transarcolemmal sodium and potassium gradients, crucial for cardiac cell electrophysiology. Importantly, sodium-potassium pump activity is impaired in a number of major diseased conditions, including ischemia and heart failure. However, its subtle ways of action on cardiac electrophysiology, both directly through its electrogenic nature and indirectly via the regulation of cell homeostasis, make it hard to predict the electrophysiological consequences of reduced sodium-potassium pump activity in cardiac repolarization. In this review, we discuss how recent studies adopting the Systems Biology approach, through the integration of experimental and modeling methodologies, have identified the sodium-potassium pump as one of the most\ud
important ionic mechanisms in regulating key properties of cardiac repolarization and its rate-dependence, from subcellular to whole organ levels. These include the role of the pump in the biphasic modulation of cellular repolarization and refractoriness, the rate control of intracellular sodium and calcium dynamics and therefore of the adaptation of repolarization to changes in heart rate, as well as its importance in regulating pro-arrhythmic substrates through modulation of dispersion of repolarization and restitution. Theoretical findings are consistent across a variety of cell types and species including human, and widely in agreement with experimental findings. The novel insights and hypotheses on the role of the pump in cardiac electrophysiology obtained through this integrative approach could eventually lead to novel therapeutic and diagnostic strategies
Chaste: an open source C++ library for computational physiology and biology
Chaste - Cancer, Heart And Soft Tissue Environment - is an open source C++ library for the computational simulation of mathematical models developed for physiology and biology. Code development has been driven by two initial applications: cardiac electrophysiology and cancer development. A large number of cardiac electrophysiology studies have been enabled and performed, including high performance computational investigations of defibrillation on realistic human cardiac geometries. New models for the initiation and growth of tumours have been developed. In particular, cell-based simulations have provided novel insight into the role of stem cells in the colorectal crypt. Chaste is constantly evolving and is now being applied to a far wider range of problems. The code provides modules for handling common scientific computing components, such as meshes and solvers for ordinary and partial differential equations (ODEs/PDEs). Re-use of these components avoids the need for researchers to "re-invent the wheel" with each new project, accelerating the rate of progress in new applications. Chaste is developed using industrially-derived techniques, in particular test-driven development, to ensure code quality, re-use and reliability. In this article we provide examples that illustrate the types of problems Chaste can be used to solve, which can be run on a desktop computer. We highlight some scientific studies that have used or are using Chaste, and the insights they have provided. The source code, both for specific releases and the development version, is available to download under an open source Berkeley Software Distribution (BSD) licence at http://www.cs.ox.ac.uk/chaste, together with details of a mailing list and links to documentation and tutorials
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