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

There is considerable spatial heterogeneity in the electrical properties of the heart muscle and there are indications that anisotropic conduction may play an important role in the pathogenesis of clinical cardiac arrhythmias. Spiral waves of electrical activity are related to reentrant cardiac arrhythmias as ventricular tachycardia and ventricular fibrillation, and the generation of a wave breakup is hypothesized to underlie the transition from ventricular tachycardia to ventricular fibrillation — the leading cause of sudden cardiac death. Here we investigate the effect of heterogeneity on spiral wave reentry in a two-dimensional modified FitzHugh–Nagumo membrane model. Spiral wave breakup induced by the heterogeneity is found. The spiral wave dynamics is invariant under translational and rotational transformations in homogeneous tissue, but for heterogeneous tissue, this symmetry is broken due to the heterogeneity. The reentry dynamics depends on the degree of heterogeneity and the point where the reentry is initiated within the simulated tissue. This study may open potentially exciting new diagnostic and therapeutic possibilities in a clinical context.

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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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Drift and termination of spiral waves in optogenetically modified cardiac tissue at sub-threshold illumination

eLife ◽

10.7554/elife.59954 ◽

2021 ◽

Vol 10 ◽

Cited By ~ 1

Author(s):

Sayedeh Hussaini ◽

Vishalini Venkatesan ◽

Valentina Biasci ◽

José M Romero Sepúlveda ◽

Raul A Quiñonez Uribe ◽

...

Keyword(s):

Cardiac Tissue ◽

Dynamic Control ◽

Spiral Wave ◽

Deep Understanding ◽

Spiral Waves ◽

Mouse Heart ◽

Cell Coupling ◽

Wave Dynamics ◽

Systematic Exploration ◽

Voltage Gradients

The development of new approaches to control cardiac arrhythmias requires a deep understanding of spiral wave dynamics. Optogenetics offers new possibilities for this. Preliminary experiments show that sub-threshold illumination affects electrical wave propagation in the mouse heart. However, a systematic exploration of these effects is technically challenging. Here, we use state-of-the-art computer models to study the dynamic control of spiral waves in a two-dimensional model of the adult mouse ventricle, using stationary and non-stationary patterns of sub-threshold illumination. Our results indicate a light-intensity-dependent increase in cellular resting membrane potentials, which together with diffusive cell-cell coupling leads to the development of spatial voltage gradients over differently illuminated areas. A spiral wave drifts along the positive gradient. These gradients can be strategically applied to ensure drift-induced termination of a spiral wave, both in optogenetics and in conventional methods of electrical defibrillation.

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Drift and termination of spiral waves in optogenetically modified cardiac tissue at sub-threshold illumination

10.1101/2020.06.12.148734 ◽

2020 ◽

Cited By ~ 1

Author(s):

Sayedeh Hussaini ◽

Vishalini Venkatesan ◽

Valentina Biasci ◽

José M. Romero Sepúlveda ◽

Raúl A. Quiñonez Uribe ◽

...

Keyword(s):

Cardiac Tissue ◽

Dynamic Control ◽

Spiral Wave ◽

Deep Understanding ◽

Spiral Waves ◽

Mouse Heart ◽

Cell Coupling ◽

Wave Dynamics ◽

Systematic Exploration ◽

Voltage Gradients

AbstractThe development of new approaches to control cardiac arrhythmias requires a deep understanding of spiral wave dynamics. Optogenetics offers new possibilities for this. Preliminary experiments show that sub-threshold illumination affects electrical wave propagation in the mouse heart. However, a systematic exploration of these effects is technically challenging. Here, we use state-of-the-art computer models to study the dynamic control of spiral waves in a two-dimensional model of the adult mouse ventricle, using stationary and non-stationary patterns of sub-threshold illumination. Our results indicate a light intensity-dependent increase in cellular resting membrane potentials, which together with diffusive cell-cell coupling leads to the development of spatial voltage gradients over differently illuminated areas. A spiral wave drifts along the positive gradient. These gradients can be strategically applied to ensure drift-induced termination of a spiral wave, both in optogenetics and in conventional methods of electrical defibrillation.

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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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Alternans and spiral breakup in a human ventricular tissue model

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00109.2006 ◽

2006 ◽

Vol 291 (3) ◽

pp. H1088-H1100 ◽

Cited By ~ 574

Author(s):

K. H. W. J. ten Tusscher ◽

A. V. Panfilov

Keyword(s):

Cardiac Tissue ◽

Cell Model ◽

Sodium Current ◽

Single Cells ◽

Spiral Wave ◽

Western World ◽

Cardiac Memory ◽

Electrical Instability ◽

Ventricular Tissue ◽

Human Cardiac Tissue

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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