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A V Panfilov

Publications and source records attributed to A V Panfilov.

At least 19 recordsLinked to original sources
PubMed2006

Cell model for efficient simulation of wave propagation in human ventricular tissue under normal and pathological conditions.

In this paper, we formulate a model for human ventricular cells that is efficient enough for whole organ arrhythmia simulations yet detailed enough to capture the effects of cell level processes such as current blocks and channelopathies. The model is obtained from our detailed human ventricular cell model by using mathematical techniques to reduce the number of variables from 19 to nine. We carefully compare our full and reduced model at the single cell, cable and 2D tissue level and show that the reduced model has a very similar behaviour. Importantly, the new model correctly produces the effects of current blocks and channelopathies on AP and spiral wave behaviour, processes at the core of current day arrhythmia research. The new model is well over four times more efficient than the full model. We conclude that the new model can be used for efficient simulations of the effects of current changes on arrhythmias in the human heart.

Action Potentials↗
PubMed2006

Alternans and spiral breakup in a human ventricular tissue model.

Ventricular fibrillation (VF) is one of the main causes of death in the Western world. According to one hypothesis, the chaotic excitation dynamics during VF are the result of dynamical instabilities in action potential duration (APD) the occurrence of which requires that the slope of the APD restitution curve exceeds 1. Other factors such as electrotonic coupling and cardiac memory also determine whether these instabilities can develop. In this paper we study the conditions for alternans and spiral breakup in human cardiac tissue. Therefore, we develop a new version of our human ventricular cell model, which is based on recent experimental measurements of human APD restitution and includes a more extensive description of intracellular calcium dynamics. We apply this model to study the conditions for electrical instability in single cells, for reentrant waves in a ring of cells, and for reentry in two-dimensional sheets of ventricular tissue. We show that an important determinant for the onset of instability is the recovery dynamics of the fast sodium current. Slower sodium current recovery leads to longer periods of spiral wave rotation and more gradual conduction velocity restitution, both of which suppress restitution-mediated instability. As a result, maximum restitution slopes considerably exceeding 1 (up to 1.5) may be necessary for electrical instability to occur. Although slopes necessary for the onset of instabilities found in our study exceed 1, they are within the range of experimentally measured slopes. Therefore, we conclude that steep APD restitution-mediated instability is a potential mechanism for VF in the human heart.

Action Potentials↗
PubMed2005

Self-organized pacemakers in a coupled reaction-diffusion-mechanics system.

Using a computational model of a coupled reaction-diffusion-mechanics system, we find that mechanical deformation can induce automatic pacemaking activity. Pacemaking is shown to occur after a single electrical or mechanical stimulus in an otherwise nonoscillatory medium. We study the mechanisms underpinning this effect and conditions for its existence. We show that self-organized pacemakers drift throughout the medium to approach attractors with locations that depend on the size of the medium, and on the location of the initial stimulus.

Action Potentials↗
PubMed2005

Scroll waves meandering in a model of an excitable medium.

We study numerically the dynamics of a scroll wave in a three-dimensional (3D) excitable medium in the presence of substantial meandering of the corresponding 2D spiral wave in the Aliev-Panfilov model. We identify three types of dynamics of the scroll wave filament--quasi-2D, periodic, and aperiodic meandering--and we study their dependence on parameter settings and thickness of the medium.

Animals↗
PubMed2005

Phase singularities and filaments: simplifying complexity in computational models of ventricular fibrillation.

In the whole heart, millions of cardiac cells are involved in ventricular fibrillation (VF). Experimental studies indicate that VF is sustained by re-entrant activity, and that each re-entrant wave rotates around a filament of phase singularity. Filaments act as organising centres, and offer a way to simplify and quantify the complex spatio-temporal behaviour observed in VF. Where a filament touches the surface of fibrillating myocardium re-entrant activity can be observed, however the behaviour of filaments within bulk ventricular myocardium is difficult to observe directly using present experimental techniques. Large scale computational simulations of VF in three-dimensional (3D) tissue offer a tool to investigate the properties and behaviour of filaments, and the aim of this paper is to review recent advances in this area as well as to compare recent computational studies of fibrillation in whole ventricle geometries.

Animals↗
PubMed2004

Eikonal formulation of the minimal principle for scroll wave filaments.

Recently, Wellner et al. [Proc. Natl. Acad. Sci. U.S.A. 99, 8015 (2002)]] proposed a principle for predicting a stable scroll wave filament shape as a geodesic in a 3D space with a metric determined by the inverse diffusivity tensor of the medium. Using the Hamilton-Jacobi theory we show that this geodesic is the shortest path for a wave propagating through the medium. This allows the use of shortest path algorithms to predict filament shapes, which we confirm numerically for a medium with orthotropic anisotropy. Our method can be used in cardiac tissue experiments since it does not require knowledge of the tissue anisotropy.

Algorithms↗
PubMed2003

Influence of nonexcitable cells on spiral breakup in two-dimensional and three-dimensional excitable media.

We study spiral wave dynamics in the presence of nonexcitable cells in two-dimensional (2D) and three-dimensional (3D) excitable media, described by the Aliev-Panfilov model. We find that increasing the percentage of randomly distributed nonexcitable cells can prevent the breaking up of a spiral wave into a complex spatiotemporal pattern. We show that this effect is more pronounced in 2D than 3D excitable media. We explain the observed 2D vs 3D differences by a different dependence of the period and diastolic interval of the spiral wave on the percentage of nonexcitable cells in 2D and 3D excitable media.

Animals↗
PubMed2003

A model for human ventricular tissue.

The experimental and clinical possibilities for studying cardiac arrhythmias in human ventricular myocardium are very limited. Therefore, the use of alternative methods such as computer simulations is of great importance. In this article we introduce a mathematical model of the action potential of human ventricular cells that, while including a high level of electrophysiological detail, is computationally cost-effective enough to be applied in large-scale spatial simulations for the study of reentrant arrhythmias. The model is based on recent experimental data on most of the major ionic currents: the fast sodium, L-type calcium, transient outward, rapid and slow delayed rectifier, and inward rectifier currents. The model includes a basic calcium dynamics, allowing for the realistic modeling of calcium transients, calcium current inactivation, and the contraction staircase. We are able to reproduce human epicardial, endocardial, and M cell action potentials and show that differences can be explained by differences in the transient outward and slow delayed rectifier currents. Our model reproduces the experimentally observed data on action potential duration restitution, which is an important characteristic for reentrant arrhythmias. The conduction velocity restitution of our model is broader than in other models and agrees better with available data. Finally, we model the dynamics of spiral wave rotation in a two-dimensional sheet of human ventricular tissue and show that the spiral wave follows a complex meandering pattern and has a period of 265 ms. We conclude that the proposed model reproduces a variety of electrophysiological behaviors and provides a basis for studies of reentrant arrhythmias in human ventricular tissue.

Action Potentials↗
PubMed2003

Spiral wave stability in cardiac tissue with biphasic restitution.

Human ventricular tissue as well as several animal ventricular preparations show a biphasic shape of the action potential duration restitution curve, with a local maximum at low diastolic intervals. We study numerically how the location and properties of this nonmonotonicity affect the stability of spiral waves. We find that, depending on the slopes of the ascending and of the descending parts of the restitution curve, we can have either stable rotation of the spiral wave or spiral breakup. We identify two types of spiral breakup: one due to a steep positive slope and another due to a steep negative slope in the restitution curve. We discuss the differences in their manifestation and possible implications. We also find that increasing the slope of the descending part of the restitution curve increases the meandering of the spiral wave, due to the repeated occurrence of conduction blocks near the spiral wave tip.

Action Potentials↗
PubMed2002

Transition from ventricular fibrillation to ventricular tachycardia: a simulation study on the role of Ca(2+)-channel blockers in human ventricular tissue.

We study the effect of blocking the L-type Ca(2+)-channel on fibrillation in simulations in two-dimensional (2D) isotropic sheets of ventricular tissue and in a three-dimensional anisotropic anatomical model of human ventricles, using a previously developed model of human ventricular cells. Ventricular fibrillation (VF) was obtained as a result of spiral wave breakup and consisted of a varying number of chaotically wandering wavelets activating tissue at a frequency of about 6.0 Hz. We show that blocking the Ca(2+)-current by 75% can convert ventricular fibrillation into a periodic regime with a small number of stable spiral waves, ranging from six in 2D sheets of 25 x 25 cm to a single spiral in the anatomical model of human ventricles. The dominant frequency during this process changed to about 10.0 Hz in the 2D simulations, but to only 5.0 Hz in the whole heart simulations where a single spiral wave anchored around an anatomical obstacle. We show that the observed effects were due to a flattening of the electrical restitution curve, which prevented the generation of wave breaks and stabilized the activation patterns.

Calcium↗
PubMed2002

Reentry in heterogeneous cardiac tissue described by the Luo-Rudy ventricular action potential model.

Heterogeneity of cardiac tissue is an important factor determining the initiation and dynamics of cardiac arrhythmias. In this paper, we studied the effects of gradients of electrophysiological heterogeneity on reentrant excitation patterns using computer simulations. We investigated the dynamics of spiral waves in a two-dimensional sheet of cardiac tissue described by the Luo-Rudy phase 1 (LR1) ventricular action potential model. A gradient of action potential duration (APD) was imposed by gradually varying the local current density of K(+) current or inward rectifying K(+) current along one axis of the tissue sheet. We show that a gradient of APD resulted in spiral wave drift. This drift consisted of two components. The longitudinal (along the gradient) component was always directed toward regions of longer spiral wave period. The transverse (perpendicular to the gradient) component had a direction dependent on the direction of rotation of the spiral wave. We estimated the velocity of the drift as a function of the magnitude of the gradient and discuss its implications.

Action Potentials↗
PubMed2002

Spiral breakup in an array of coupled cells: the role of the intercellular conductance.

We study numerically how the intercellular conductance affects the process of spiral breakup in an array of coupled excitable cells. The cell dynamics are described by the Aliev-Panfilov model, and the intercellular connection is made via Ohmic elements. We find that decreasing intercellular conductance can prevent the breaking up of a spiral wave into a complex spatiotemporal pattern. We study the mechanism of this effect and show that the breakup disappears because of increasing the diastolic interval of an initial spiral wave.

Action Potentials↗
PubMed2002

A computationally efficient electrophysiological model of human ventricular cells.

Recent experimental and theoretical results have stressed the importance of modeling studies of reentrant arrhythmias in cardiac tissue and at the whole heart level. We introduce a six-variable model obtained by a reformulation of the Priebe-Beuckelmann model of a single human ventricular cell. The reformulated model is 4.9 times faster for numerical computations and it is more stable than the original model. It retains the action potential shape at various frequencies, restitution of action potential duration, and restitution of conduction velocity. We were able to reproduce the main properties of epicardial, endocardial, and M cells by modifying selected ionic currents. We performed a simulation study of spiral wave behavior in a two-dimensional sheet of human ventricular tissue and showed that spiral waves have a frequency of 3.3 Hz and a linear core of approximately 50-mm diameter that rotates with an average frequency of 0.62 rad/s. Simulation results agreed with experimental data. In conclusion, the proposed model is suitable for efficient and accurate studies of reentrant phenomena in human ventricular tissue.

Action Potentials↗
PubMed2001

Spiral waves in excitable media with negative restitution.

We study numerically the dynamics of spiral waves in an excitable medium with negative restitution. For our study we use two models of the excitable medium: a cellular automaton and a reaction-diffusion model. There are no significant effects of negative restitution as long as the slope of the restitution curve is less steep than -1. In media with slopes steeper than -1, the dynamics of spiral waves can change significantly: (1) the average restitution time jumps to a value where the slope of the restitution curve is about -1; (2) spiral waves can break up into turbulent patterns. We discuss a possible connection between such instabilities and fibrillation in atrial tissue.

Animals↗
PubMed2000

Elimination of spiral waves in cardiac tissue by multiple electrical shocks.

We study numerically the elimination of a spiral wave in cardiac tissue by application of multiple shocks of external current. To account for the effect of shocks we apply a recently developed theory for the interaction of the external current with cardiac tissue. We compare two possible feedback algorithms for timing of the shocks: a "local" feedback algorithm 11 (using an external electrode placed directly on the tissue) and a "global" feedback algorithm 22 (using the electrocardiogram). Our main results are: application of the external current causes a parametric resonant drift similar to that reported in previous model computations; the ratio of the threshold of elimination of the spiral wave by multiple shocks to the threshold of conventional single shock defibrillation in our model for cardiac tissue is about 0.5, while earlier, less realistic models predicted the value about 0.2; we show that an important factor for successful defibrillation is the location of the feedback electrode and the best results are achieved if the feedback electrode or the ECG lead is located at the boundary (or edge) of the cardiac tissue; the "local" and the "global" feedback algorithms show similar efficiency.

Algorithms↗
PubMed1999

Three-dimensional organization of electrical turbulence in the heart.

Three-dimensional organization of electrical turbulence that is induced via the phenomenon of spiral breakup is studied in a computer model of the heart, which includes realistic ventricular geometries and cardiac anisotropy. We find filaments of rotors during the turbulence and study their number and length as a function of the heart size. We perform a dimensional analysis of turbulence.

Journal Article↗