Initiation and dynamics of a spiral wave around an ionic heterogeneity in a model for human cardiac tissue

In relation to cardiac arrhythmias, heterogeneity of cardiac tissue is one of the most important factors underlying the onset of spiral waves and determining their type. In this paper, we numerically model heterogeneity of realistic size and value and study formation and dynamics of spiral waves around such heterogeneity. We find that the only sustained pattern obtained is a single spiral wave anchored around the heterogeneity. Dynamics of an anchored spiral wave depend on the extent of heterogeneity, and for certain heterogeneity size, we find abrupt regional increase in the period of excitation occurring as a bifurcation. We study factors determining spatial distribution of excitation periods of anchored spiral waves and discuss consequences of such dynamics for cardiac arrhythmias and possibilities for experimental testings of our predictions

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

Small size ionic heterogeneities in the human heart can attract rotors

Rotors occurring in the heart underlie the mechanisms of cardiac arrhythmias. Answering the question whether or not the location of rotors is related to local properties of cardiac tissue has important practical applications. This is because ablation of rotors has been shown to be an effective way to fight cardiac arrhythmias. In this study, we investigate, in silico, the dynamics of rotors in 2D and in an anatomical model of human ventricles using a TNNP model for ventricular cells. We study the effect of small size ionic heterogeneities, similar to those measured experimentally. It is shown that such heterogeneities can not only anchor, but can also attract rotors rotating at a substantial distance from the heterogeneity. This attraction distance depends on the extent of the heterogeneities and can be as large as 5-6 cm in realistic conditions. We conclude that small size ionic heterogeneities can be preferred localization points for rotors, and discuss their possible mechanism and value for applications

Decreased repolarization reserve increases defibrillation threshold by favoring early afterdepolarizations in an in silico model of human ventricular tissue

Cardiolog

Action potential duration heterogeneity of cardiac tissue can be evaluated from cell properties using Gaussian Green's function approach.

Action potential duration (APD) heterogeneity of cardiac tissue is one of the most important factors underlying initiation of deadly cardiac arrhythmias. In many cases such heterogeneity can be measured at tissue level only, while it originates from differences between the individual cardiac cells. The extent of heterogeneity at tissue and single cell level can differ substantially and in many cases it is important to know the relation between them. Here we study effects from cell coupling on APD heterogeneity in cardiac tissue in numerical simulations using the ionic TP06 model for human cardiac tissue. We show that the effect of cell coupling on APD heterogeneity can be described mathematically using a Gaussian Green's function approach. This relates the problem of electrotonic interactions to a wide range of classical problems in physics, chemistry and biology, for which robust methods exist. We show that, both for determining effects of tissue heterogeneity from cell heterogeneity (forward problem) as well as for determining cell properties from tissue level measurements (inverse problem), this approach is promising. We illustrate the solution of the forward and inverse problem on several examples of 1D and 2D systems

Solution of the inverse problem in 2D.

<p>A: The predicted values for a measured distribution given by <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0079607#pone-0079607-g001" target="_blank">Fig. 1A</a>. Regularization parameter is . B: The exact solution.</p

Effect of wave propagation in 2D.

<p>A: Upper panel: APD distribution obtained by wave propagating from the left boundary. Lower panel: APD distribution along the horizontal line through the center. In black for simultaneous stimulation of all cells as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0079607#pone-0079607-g001" target="_blank">Fig. 1A</a>. In red for stimulation from the left boundary. B: Upper panel: APD distribution obtained by wave propagating from the upper boundary. Lower panel: APD distribution along the vertical line through the center. In black for simultaneous stimulation of all cells. In red for stimulation from the upper boundary.</p