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

2003 ◽  
Vol 284 (2) ◽  
pp. H542-H548 ◽  
Author(s):  
K. H. W. J. Ten Tusscher ◽  
A. V. Panfilov

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.

1999 ◽  
Vol 276 (1) ◽  
pp. H269-H283 ◽  
Author(s):  
Zhilin Qu ◽  
James N. Weiss ◽  
Alan Garfinkel

Spiral wave breakup is a proposed mechanism underlying the transition from ventricular tachycardia to fibrillation. We examined the importance of the restitution of action potential duration (APD) and of conduction velocity (CV) to the stability of spiral wave reentry in a two-dimensional sheet of simulated cardiac tissue. The Luo-Rudy ventricular action potential model was modified to eliminate its restitution properties, which are caused by deactivation or recovery from inactivation of K+, Ca2+, and Na+ currents ( I K, I Ca, and I Na, respectively). In this model, we find that 1) restitution of I Ca and I Na are the main determinants of the steepness of APD restitution; 2) for promoting spiral breakup, the range of diastolic intervals over which the APD restitution slope is steep is more important than the maximum steepness; 3) CV restitution promotes spiral wave breakup independently of APD restitution; and 4) “defibrillation” of multiple spiral wave reentry is most effectively achieved by combining an antifibrillatory intervention based on altering restitution with an antitachycardia intervention. These findings suggest a novel paradigm for developing effective antiarrhythmic drugs.


2003 ◽  
Vol 13 (12) ◽  
pp. 3865-3871 ◽  
Author(s):  
O. V. ASLANIDI ◽  
R. H. CLAYTON ◽  
A. V. HOLDEN ◽  
H. K. PHILLIPS ◽  
R. J. WARD

The vulnerable window in a heterogeneous virtual LRl cardiac tissue, with a linear gradient in GK, is wider when following propagation down the gradient, towards tissue with longer action potential duration, than when following propagation up the gradient. Spiral wave solutions in a uniform linear gradient in GK drift, with a velocity component along the gradient of the order of mm/s, towards tissue with a longer APD.


2001 ◽  
Vol 280 (2) ◽  
pp. H535-H545 ◽  
Author(s):  
Fagen Xie ◽  
Zhilin Qu ◽  
Alan Garfinkel ◽  
James N. Weiss

Generation of wave break is a characteristic feature of cardiac fibrillation. In this study, we investigated how dynamic factors and fixed electrophysiological heterogeneity interact to promote wave break in simulated two-dimensional cardiac tissue, by using the Luo-Rudy (LR1) ventricular action potential model. The degree of dynamic instability of the action potential model was controlled by varying the maximal amplitude of the slow inward Ca2+ current to produce spiral waves in homogeneous tissue that were either nearly stable, meandering, hypermeandering, or in breakup regimes. Fixed electrophysiological heterogeneity was modeled by randomly varying action potential duration over different spatial scales to create dispersion of refractoriness. We found that the degree of dispersion of refractoriness required to induce wave break decreased markedly as dynamic instability of the cardiac model increased. These findings suggest that reducing the dynamic instability of cardiac cells by interventions, such as decreasing the steepness of action potential duration restitution, may still have merit as an antifibrillatory strategy.


2002 ◽  
Vol 282 (6) ◽  
pp. H2296-H2308 ◽  
Author(s):  
O. Bernus ◽  
R. Wilders ◽  
C. W. Zemlin ◽  
H. Verschelde ◽  
A. V. Panfilov

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 ∼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.


Author(s):  
Samuel R Kuo ◽  
Natalia A Trayanova

Atrial fibrillation (AF) is believed to be perpetuated by recirculating spiral waves. Atrial structures are often characterized with action potentials of varying morphologies; however, the role of the structure-dependent atrial electrophysiological heterogeneity in spiral wave behaviour is not well understood. The purpose of this study is to determine the effect of action potential morphology heterogeneity associated with the major atrial structures in spiral wave maintenance. The present study also focuses on how this effect is further modulated by the presence of the inherent periodicity in atrial structure. The goals of the study are achieved through the simulation of electrical behaviour in a two-dimensional atrial tissue model that incorporates the representation of action potentials in various structurally distinct regions in the right atrium. Periodic boundary conditions are then imposed to form a cylinder (quasi three-dimensional), thus allowing exploration of the additional effect of structure periodicity on spiral wave behaviour. Transmembrane potential maps and phase singularity traces are analysed to determine effects on spiral wave behaviour. Results demonstrate that the prolonged refractoriness of the crista terminalis (CT) affects the pattern of spiral wave reentry, while the variation in action potential morphology of the other structures does not. The CT anchors the spiral waves, preventing them from drifting away. Spiral wave dynamics is altered when the ends of the sheet are spliced together to form a cylinder. The main effect of the continuous surface is the generation of secondary spiral waves which influences the primary rotors. The interaction of the primary and secondary spiral waves decreased as cylinder diameter increased.


Author(s):  
Stephen D. McIntyre ◽  
Yoichiro Mori ◽  
Elena G. Tolkacheva

A beat-to-beat variation in cardiac action potential durations (APD) is a phenomenon known as electrical alternans. Alternans desynchronizes depolarization, increases dispersion of refractoriness and creates a substrate for ventricular fibrillation. In the heart, APD alternans can be accompanied by alternans in intracellular calcium ([Ca2+]i) transients. Recently, we demonstrated experimentally that the onset of APD alternans in the heart is a local phenomenon that undergoes complex spatiotemporal dynamics as pacing rate increases. Moreover, the local onset of APD alternans can be predicted by measuring the restitution properties of periodically paced cardiac tissue. The purpose of this research is to investigate the interplay between local onsets of APD and [Ca2+]i alternans using 2D simulation of action potential model of cardiac myocytes.


2008 ◽  
Vol 94 (2) ◽  
pp. 392-410 ◽  
Author(s):  
Aman Mahajan ◽  
Yohannes Shiferaw ◽  
Daisuke Sato ◽  
Ali Baher ◽  
Riccardo Olcese ◽  
...  

2001 ◽  
Vol 280 (4) ◽  
pp. H1667-H1673 ◽  
Author(s):  
Fagen Xie ◽  
Zhilin Qu ◽  
Alan Garfinkel ◽  
James N. Weiss

Regional hyperkalemia during acute myocardial ischemia is a major factor promoting electrophysiological abnormalities leading to ventricular fibrillation (VF). However, steep action potential duration restitution, recently proposed to be a major determinant of VF, is typically decreased rather than increased by hyperkalemia and acute ischemia. To investigate this apparent contradiction, we simulated the effects of regional hyperkalemia and other ischemic components (anoxia and acidosis) on the stability of spiral wave reentry in simulated two-dimensional cardiac tissue by use of the Luo-Rudy ventricular action potential model. We found that the hyperkalemic “ischemic” area promotes wavebreak in the surrounding normal tissue by accelerating the rate of spiral wave reentry, even after the depolarized ischemic area itself has become unexcitable. Furthermore, wavebreak and fibrillation can be prevented if the dynamical instability of the normal tissue is reduced significantly by targeting electrical restitution properties, suggesting a novel therapeutic approach.


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