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.

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Electrical refractory period restitution and spiral wave reentry in simulated cardiac tissue

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00898.2001 ◽

2002 ◽

Vol 283 (1) ◽

pp. H448-H460 ◽

Cited By ~ 41

Author(s):

Fagen Xie ◽

Zhilin Qu ◽

Alan Garfinkel ◽

James N. Weiss

Keyword(s):

Refractory Period ◽

Cardiac Tissue ◽

Cell Model ◽

Experimental Studies ◽

Spiral Wave ◽

Transmembrane Potentials ◽

Wave Stability ◽

Cardiac Action ◽

Ventricular Tissue ◽

Atrial Cell

Theoretical and experimental studies have shown that restitution of the cardiac action potential (AP) duration (APD) plays a major role in predisposing ventricular tachycardia to degenerate to ventricular fibrillation, whereas its role in atrial fibrillation is unclear. We used the Courtemanche human atrial cell model and the Luo-Rudy guinea pig ventricular model to compare the roles of electrical restitution in destabilizing spiral wave reentry in simulated two-dimensional homogeneous atrial and ventricular tissue. Because atrial AP morphology is complex, we also validated the usefulness of effective refractory period (ERP) restitution. ERP restitution correlated best with APD restitution at transmembrane potentials greater than or equal to −62 mV, and its steepness was a reliable predictor of spiral wave phenotype (stable, meandering, hypermeandering, and breakup) in both atrial and ventricular tissue. Spiral breakup or single hypermeandering spirals occurred when the slope of ERP restitution exceeded 1 at short diastolic intervals. Thus ERP restitution, which is easier to measure clinically than APD restitution, is a reliable determinant of spiral wave stability in simulated atrial and ventricular tissue.

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A computationally efficient electrophysiological model of human ventricular cells

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00731.2001 ◽

2002 ◽

Vol 282 (6) ◽

pp. H2296-H2308 ◽

Cited By ~ 94

Author(s):

O. Bernus ◽

R. Wilders ◽

C. W. Zemlin ◽

H. Verschelde ◽

A. V. Panfilov

Keyword(s):

Action Potential ◽

Cardiac Tissue ◽

Spiral Wave ◽

Ionic Currents ◽

Average Frequency ◽

Computationally Efficient ◽

Variable Model ◽

Potential Shape ◽

Ventricular Cells ◽

Ventricular Tissue

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.

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VULNERABILITY TO REENTRY, AND DRIFT, STABILITY AND BREAKDOWN OF SPIRAL WAVES IN A LINEAR GRADIENT OF GK IN A LUO–RUDY 1 VIRTUAL VENTRICULAR TISSUE

International Journal of Bifurcation and Chaos ◽

10.1142/s0218127403009010 ◽

2003 ◽

Vol 13 (12) ◽

pp. 3865-3871 ◽

Cited By ~ 2

Author(s):

O. V. ASLANIDI ◽

R. H. CLAYTON ◽

A. V. HOLDEN ◽

H. K. PHILLIPS ◽

R. J. WARD

Keyword(s):

Action Potential ◽

Velocity Component ◽

Action Potential Duration ◽

Cardiac Tissue ◽

Spiral Wave ◽

Spiral Waves ◽

Linear Gradient ◽

Wave Solutions ◽

Ventricular Tissue ◽

Vulnerable Window

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.

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A Discrete Electromechanical Model for Human Cardiac Tissue: Effects of Stretch-Activated Currents and Stretch Conditions on Restitution Properties and Spiral Wave Dynamics

PLoS ONE ◽

10.1371/journal.pone.0059317 ◽

2013 ◽

Vol 8 (3) ◽

pp. e59317 ◽

Cited By ~ 27

Author(s):

Louis D. Weise ◽

Alexander V. Panfilov

Keyword(s):

Cardiac Tissue ◽

Spiral Wave ◽

Wave Dynamics ◽

Electromechanical Model ◽

Tissue Effects ◽

Human Cardiac Tissue

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Correction: A Discrete Electromechanical Model for Human Cardiac Tissue: Effects of Stretch-Activated Currents and Stretch Conditions on Restitution Properties and Spiral Wave Dynamics

PLoS ONE ◽

10.1371/annotation/9ceadf50-eb8f-4051-9e41-772884d47385 ◽

2013 ◽

Vol 8 (6) ◽

Cited By ~ 8

Author(s):

Louis D. Weise ◽

Alexander V. Panfilov

Keyword(s):

Cardiac Tissue ◽

Spiral Wave ◽

Wave Dynamics ◽

Electromechanical Model ◽

Tissue Effects ◽

Human Cardiac Tissue

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

Physical Review E ◽

10.1103/physreve.88.062703 ◽

2013 ◽

Vol 88 (6) ◽

Cited By ~ 13

Author(s):

Arne Defauw ◽

Peter Dawyndt ◽

Alexander V. Panfilov

Keyword(s):

Cardiac Tissue ◽

Spiral Wave ◽

Human Cardiac Tissue

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Why Is Only Type 1 Electrocardiogram Diagnostic of Brugada Syndrome? Mechanistic Insights From Computer Modeling

Circulation Arrhythmia and Electrophysiology ◽

10.1161/circep.121.010365 ◽

2021 ◽

Author(s):

Zhaoyang Zhang ◽

Peng-Sheng Chen ◽

James N. Weiss ◽

Zhilin Qu

Keyword(s):

Brugada Syndrome ◽

Potassium Current ◽

Sodium Current ◽

Single Cells ◽

Spiral Wave ◽

Potassium Currents ◽

Delayed Rectifier ◽

Late Sodium Current

Background: Three types of characteristic ST-segment elevation are associated with Brugada syndrome but only type 1 is diagnostic. Why only type 1 ECG is diagnostic remains unanswered. Methods: Computer simulations were performed in single cells, 1-dimensional cables, and 2-dimensional tissues to investigate the effects of the peak and late components of the transient outward potassium current (I to ), sodium current, and L-type calcium current (I Ca,L ) as well as other potassium currents on the genesis of ECG morphologies and phase 2 reentry (P2R). Results: Although a sufficiently large peak I to was required to result in the type 1 ECG pattern and P2R, increasing the late component of I to converted type 1 ECG to type 2 ECG and suppressed P2R. Increasing the peak I to promoted spiral wave breakup, potentiating the transition from tachycardia to fibrillation, but increasing the late I to prevented spiral wave breakup by flattening the action potential duration restitution and preventing P2R. A sufficiently large I Ca,L conductance was needed for P2R to occur, but once above the critical conductance, blocking I Ca,L promoted P2R. However, selectively blocking the window and late components of I Ca,L suppressed P2R, countering the effect of the late I to . Blocking either the peak or late components of sodium current promoted P2R, with the late sodium current blockade having the larger effect. As expected, increasing other potassium currents potentiated P2R, with ATP-sensitive potassium current exhibiting a larger effect than rapid and slow component of the delayed rectifier potassium current. Conclusions: The peak I to promotes type 1 ECG and P2R, whereas the late I to converts type 1 ECG to type 2 ECG and suppresses P2R. Blocking the peak I Ca,L and either the peak or the late sodium current promotes P2R, whereas blocking the window and late I Ca,L suppresses P2R. These results provide important insights into the mechanisms of arrhythmogenesis and potential therapeutic targets for treatment of Brugada syndrome.

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Turbulent electrical activity at sharp-edged inexcitable obstacles in a model for human cardiac tissue

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00593.2013 ◽

2014 ◽

Vol 307 (7) ◽

pp. H1024-H1035 ◽

Cited By ~ 12

Author(s):

Rupamanjari Majumder ◽

Rahul Pandit ◽

A. V. Panfilov

Keyword(s):

Wave Propagation ◽

Cardiac Tissue ◽

Spiral Wave ◽

Spiral Waves ◽

Delayed Rectifier ◽

High Frequency Stimulation ◽

Secondary Importance ◽

Ionic Model ◽

Delayed Rectifier Current ◽

Human Cardiac Tissue

Wave propagation around various geometric expansions, structures, and obstacles in cardiac tissue may result in the formation of unidirectional block of wave propagation and the onset of reentrant arrhythmias in the heart. Therefore, we investigated the conditions under which reentrant spiral waves can be generated by high-frequency stimulation at sharp-edged obstacles in the ten Tusscher-Noble-Noble-Panfilov (TNNP) ionic model for human cardiac tissue. We show that, in a large range of parameters that account for the conductance of major inward and outward ionic currents of the model [fast inward Na+ current ( INa), L—type slow inward Ca2+ current ( ICaL), slow delayed-rectifier current ( IKs), rapid delayed-rectifier current ( IKr), inward rectifier K+ current ( IK1)], the critical period necessary for spiral formation is close to the period of a spiral wave rotating in the same tissue. We also show that there is a minimal size of the obstacle for which formation of spirals is possible; this size is ∼2.5 cm and decreases with a decrease in the excitability of cardiac tissue. We show that other factors, such as the obstacle thickness and direction of wave propagation in relation to the obstacle, are of secondary importance and affect the conditions for spiral wave initiation only slightly. We also perform studies for obstacle shapes derived from experimental measurements of infarction scars and show that the formation of spiral waves there is facilitated by tissue remodeling around it. Overall, we demonstrate that the formation of reentrant sources around inexcitable obstacles is a potential mechanism for the onset of cardiac arrhythmias in the presence of a fast heart rate.

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