Defauw A, Vandersickel N, Dawyndt P, Panfilov AV. Small size ionic heterogeneities in the human heart can attract rotors. Am J Physiol Heart Circ Physiol 307: H1456 -H1468, 2014. First published September 12, 2014 doi:10.1152/ajpheart.00410.2014.-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 two-dimensional and in an anatomical model of human ventricles using a Ten Tusscher-NobleNoble-Panfilov (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 cannot 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. cardiac arrhythmias; computer modeling; reentry; rotors; heterogeneity; attractors SUDDEN CARDIAC DEATH IS THE largest cause of mortality in the industrialized world, accounting for more than 400,000 deaths per year in the United States alone (8). In most of the cases, it occurs as a result of cardiac arrhythmias. Therefore, it is important to study the mechanism of initiation of cardiac arrhythmias, to study the factors affecting arrhythmia initiation and dynamics, and to find new ways to manage them. These phenomena are studied using a wide variety of methods, including experimental and clinical research as well as computer modeling.One of the most important mechanisms of arrhythmias are reentrant sources of excitation, which may form spiral waves also called rotors. Rotors were first predicted in modeling studies (29) and then discovered experimentally (1, 4). Recently, they have attracted a lot of attention, as clinical studies by the group of Narayan et el. (17, 18) showed that identification and ablation of these rotors can result in termination or slowing of atrial fibrillation. Similar research is being done in the ventricles (10). Thus factors that determine the formation of rotors and the possible position of rotors in the heart are of great practical interest. Therefore, it is of paramount importance to know whether the final position of the rotor is affected by specific local properties (substrate) of cardiac tissue.From a general point of view, prevalence of a rotor at a specific position can be the result of the formation of a rotor at a given place, or it can be due to some process that brings the rotor from one location to another and stabilizes it there. It is well known that a rotor can be locally sta...
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.
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.
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.
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