Electrophysiological and structural determinants of electrotonic modulation of repolarization by the activation sequence

Walton, Richard D.; Benson, Alan P.; Hardy, Matthew E.L.; White, Edward; Bernus, Olivier

doi:10.3389/fphys.2013.00281

Cited by 25 publications

(30 citation statements)

References 39 publications

(66 reference statements)

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“…where D 1 , D 2 , and D 3 correspond to 'electrical diffusion' in directions along the myocyte orientation axis, perpendicular to myocyte orientation in the sheetlet plane, and normal to the sheetlet plane, respectively, e 1 , e 2 , and e 3 are the corresponding eigenvectors obtained from DTI, and the superscript T denotes the vector transpose. D 1 was set to a value which gave a conduction velocity of 0.6 m/s along the myocyte orientation axis [10]. For isotropic simulations, the diffusion coefficients, D i , were set equal to each other, and were scaled (by reducing values radial to the myocyte direction) in the ratios For 5000 ms arrhythmia simulations, conduction velocity was decreased by 50% to facilitate sustenance of re-entry.…”

Section: Ventricular Tissue Simulationsmentioning

confidence: 99%

Role of Cardiac Microstructure Variability on Ventricular Arrhythmogenesis

Whittaker

Benson

Teh

et al. 2018

2018 Computing in Cardiology Conference (CinC)

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The propagation of cardiac electrical excitation is influenced by tissue microstructure. Reaction-diffusion computational models of cardiac electrophysiology incorporating both dynamic action potential (AP) behaviour and image-based myocardial architecture provide an approach to study the complex organisation of excitation waves within variable myocardial structures. The role of tissue microstructure (cardiomyocyte and sheetlet orientations) on organ-scale arrhythmic excitations was investigated. Five healthy rat ventricle datasets were obtained using diffusion tensor MRI (DTI). The Fenton-Karma minimal AP model was modified to reproduce the rat AP duration and restitution. Re-entrant scroll waves were initiated in the five anatomical models at ten locations for three microstructure scenarios: (i) isotropic; (ii) anisotropic; and (iii) orthotropic. Variability in anatomy and microstructure caused simulated scroll waves to self-terminate, remain tachycardia-like, or degenerate into fibrillatory activity. Whilst inclusion of DTI-based microstructure increased total scroll wave filament length to differing extents between the five hearts, overall mean filament dynamics were quantitatively similar under anisotropic and orthotropic conditions. This study highlights the important role of inter-subject structural variability.

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Section: Ventricular Tissue Simulationsmentioning

confidence: 99%

Role of Cardiac Microstructure Variability on Ventricular Arrhythmogenesis

Whittaker

Benson

Teh

et al. 2018

2018 Computing in Cardiology Conference (CinC)

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“…Therefore, with a given intrinsic difference in APD between the two myocardial regions, a spatial disparity in the final repolarization time could be either amplified or attenuated depending on whether these regions are activated at the same time point, or the activation in one region is postponed relative to the other. High‐resolution mapping of ventricular depolarization in human subjects and various animal models (dog, rabbit, pig, and rat) suggests the presence of close relationships between the sequence of electrical activation and the distribution of APD along the propagation path. Under physiological conditions, the impulse propagation from the site of earliest activation is associated with progressive shortening of APD, which is attributed to electrotonic interactions between adjacent cardiac cells.…”

Section: Activation–repolarization Couplingmentioning

confidence: 99%

“…The presence of the activation–repolarization coupling has been validated by reconstructing the epicardial, endocardial, and transmural maps of ventricular activation. Quantitatively, it could be assessed by plotting APD 90 values measured in distinct ventricular recording sites vs. corresponding activation times (Fig.…”

Section: Activation–repolarization Couplingmentioning

confidence: 99%

Role of abnormal repolarization in the mechanism of cardiac arrhythmia

Osadchii

2017

Acta Physiologica

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In cardiac patients, life-threatening tachyarrhythmia is often precipitated by abnormal changes in ventricular repolarization and refractoriness. Repolarization abnormalities typically evolve as a consequence of impaired function of outward K currents in cardiac myocytes, which may be caused by genetic defects or result from various acquired pathophysiological conditions, including electrical remodelling in cardiac disease, ion channel modulation by clinically used pharmacological agents, and systemic electrolyte disorders seen in heart failure, such as hypokalaemia. Cardiac electrical instability attributed to abnormal repolarization relies on the complex interplay between a provocative arrhythmic trigger and vulnerable arrhythmic substrate, with a central role played by the excessive prolongation of ventricular action potential duration, impaired intracellular Ca handling, and slowed impulse conduction. This review outlines the electrical activity of ventricular myocytes in normal conditions and cardiac disease, describes classical electrophysiological mechanisms of cardiac arrhythmia, and provides an update on repolarization-related surrogates currently used to assess arrhythmic propensity, including spatial dispersion of repolarization, activation-repolarization coupling, electrical restitution, TRIaD (triangulation, reverse use dependence, instability, and dispersion), and the electromechanical window. This is followed by a discussion of the mechanisms that account for the dependence of arrhythmic vulnerability on the location of the ventricular pacing site. Finally, the review clarifies the electrophysiological basis for cardiac arrhythmia produced by hypokalaemia, and gives insight into the clinical importance and pathophysiology of drug-induced arrhythmia, with particular focus on class Ia (quinidine, procainamide) and Ic (flecainide) Na channel blockers, and class III antiarrhythmic agents that block the delayed rectifier K channel (dofetilide).

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“…, Walton et al . ). Activation–repolarization coupling has been attributed to the modulation of APD in neighbouring cardiac cells by the axial current flow through gap junctions (Osaka et al .…”

Section: Discussionmentioning

confidence: 97%