The Virtual Ventricular Wall: A Tool for Exploring Cardiac Propagation and Arrhythmogenesis

Holden, Arun V.; Aslanidi, Oleg; Benson, Alan P.; Clayton, Richard H.; Halley, Graeme; Li, Pan; Tong, Wing Chiu

doi:10.1007/s10867-006-9020-1

Cited by 13 publications

(7 citation statements)

References 41 publications

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“…Effects of amiodarone are simulated by reducing the conductance of I CaL and I Ks by 40 and 50%, respectively. 37 , 38 Drug effects on the APD and its heterogeneity between the PV and LA cells are summarized in Table 2 .…”

Section: Methodsmentioning

confidence: 99%

Evolution and pharmacological modulation of the arrhythmogenic wave dynamics in canine pulmonary vein model

et al. 2014

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AimsAtrial fibrillation (AF), the commonest cardiac arrhythmia, has been strongly linked with arrhythmogenic sources near the pulmonary veins (PVs), but underlying mechanisms are not fully understood. We aim to study the generation and sustenance of wave sources in a model of the PV tissue.Methods and resultsA previously developed biophysically detailed three-dimensional canine atrial model is applied. Effects of AF-induced electrical remodelling are introduced based on published experimental data, as changes of ion channel currents (ICaL, IK1, Ito, and IKur), the action potential (AP) and cell-to-cell coupling levels. Pharmacological effects are introduced by blocking specific ion channel currents. A combination of electrical heterogeneity (AP tissue gradients of 5–12 ms) and anisotropy (conduction velocities of 0.75–1.25 and 0.21–0.31 m/s along and transverse to atrial fibres) can results in the generation of wave breaks in the PV region. However, a long wavelength (171 mm) prevents the wave breaks from developing into re-entry. Electrical remodelling leads to decreases in the AP duration, conduction velocity and wavelength (to 49 mm), such that re-entry becomes sustained. Pharmacological effects on the tissue heterogeneity and vulnerability (to wave breaks and re-entry) are quantified to show that drugs that increase the wavelength and stop re-entry (IK1 and IKur blockers) can also increase the heterogeneity (AP gradients of 26–27 ms) and the likelihood of wave breaks.ConclusionBiophysical modelling reveals large conduction block areas near the PVs, which are due to discontinuous fibre arrangement enhanced by electrical heterogeneity. Vulnerability to re-entry in such areas can be modulated by pharmacological interventions.

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Section: Methodsmentioning

confidence: 99%

Evolution and pharmacological modulation of the arrhythmogenic wave dynamics in canine pulmonary vein model

et al. 2014

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“…These models have been used to study the mechanisms of arrhythmogenesis (47,48) and to study the actions of drugs such as d-sotalol on propagation (47). We can therefore look forward to testing the actions of drugs at multiple levels including that of the whole heart.…”

Section: Linking Levels: Building the Virtual Heartmentioning

confidence: 99%

Computational Models of the Heart and Their Use in Assessing the Actions of Drugs

Noble

2008

J Pharmacol Sci

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Abstract. Models of cardiac cells are sufficiently well developed to answer questions concerning the actions of drugs on repolarization and the initiation of arrhythmias. These models can be used to characterize drug-receptor action profiles that would be expected to avoid arrhythmia and so help to identify drugs that may be safer. Several examples of such action profiles are presented here, including a recently-developed blocker of persistent sodium current, ranolazine. The models have also been incorporated into tissue and organ models that enable arrhythmia to be modelled also at these levels. Work at these levels can reproduce both re-entrant arrhythmia and fibrillation.

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“…the reviews by Benson et al [26], Clayton et al [27], Holden et al [28] and Vigmond et al [29]). Cardiac tissue is composed of muscle cells (myocytes), other supporting cells (fibroblasts), connective tissue and its blood and nerve supply.…”

Section: Introductionmentioning

confidence: 99%

Construction and validation of anisotropic and orthotropic ventricular geometries for quantitative predictive cardiac electrophysiology

et al. 2010

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Reaction -diffusion computational models of cardiac electrophysiology require both dynamic excitation models that reconstruct the action potentials of myocytes as well as datasets of cardiac geometry and architecture that provide the electrical diffusion tensor D, which determines how excitation spreads through the tissue. We illustrate an experimental pipeline we have developed in our laboratories for constructing and validating such datasets. The tensor D changes with location in the myocardium, and is determined by tissue architecture. Diffusion tensor magnetic resonance imaging (DT-MRI) provides three eigenvectors e i and eigenvalues l i at each voxel throughout the tissue that can be used to reconstruct this architecture. The primary eigenvector e 1 is a histologically validated measure of myocyte orientation (responsible for anisotropic propagation). The secondary and tertiary eigenvectors (e 2 and e 3 ) specify the directions of any orthotropic structure if l 2 is significantly greater than l 3 -this orthotropy has been identified with sheets or cleavage planes. For simulations, the components of D are scaled in the fibre and cross-fibre directions for anisotropic simulations (or fibre, sheet and sheet normal directions for orthotropic tissues) so that simulated conduction velocities match values from optical imaging or plunge electrode experiments. The simulated pattern of propagation of action potentials in the models is partially validated by optical recordings of spatio-temporal activity on the surfaces of hearts. We also describe several techniques that enhance components of the pipeline, or that allow the pipeline to be applied to different areas of research: Q ball imaging provides evidence for multi-modal orientation distributions within a fraction of voxels, infarcts can be identified by changes in the anisotropic structure-irregularity in myocyte orientation and a decrease in fractional anisotropy, clinical imaging provides human ventricular geometry and can identify ischaemic and infarcted regions, and simulations in human geometries examine the roles of anisotropic and orthotropic architecture in the initiation of arrhythmias.

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The Virtual Ventricular Wall: A Tool for Exploring Cardiac Propagation and Arrhythmogenesis

Cited by 13 publications

References 41 publications

Evolution and pharmacological modulation of the arrhythmogenic wave dynamics in canine pulmonary vein model

Evolution and pharmacological modulation of the arrhythmogenic wave dynamics in canine pulmonary vein model

Computational Models of the Heart and Their Use in Assessing the Actions of Drugs

Construction and validation of anisotropic and orthotropic ventricular geometries for quantitative predictive cardiac electrophysiology

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