Computational Cardiac Electrophysiology: Implementing Mathematical Models of Cardiomyocytes to Simulate Action Potentials of the Heart

2015 ◽  
pp. 65-74
Author(s):  
Michael M. Bell ◽  
Elizabeth M. Cherry
Keyword(s):  
Mathematical Models ◽  
Action Potentials ◽  
Cardiac Electrophysiology

Mathematical models and numerical methods for the forward problem in cardiac electrophysiology

2002 ◽  
Vol 5 (4) ◽  
pp. 215-239 ◽  
Author(s):  
G.T. Lines ◽  
M.L. Buist ◽  
P. Grottum ◽  
A.J. Pullan ◽  
J. Sundnes ◽  
...  
Keyword(s):  
Numerical Methods ◽  
Mathematical Models ◽  
Cardiac Electrophysiology ◽  
Forward Problem

scholarly journals Cardiac Transmembrane Ion Channels and Action Potentials: Cellular Physiology and Arrhythmogenic Behavior

2020 ◽  
Author(s):  
András Varró ◽  
Jakub Tomek ◽  
Norbert Nagy ◽  
Laszlo Virag ◽  
Elisa Passini ◽  
...  
Keyword(s):  
Ion Channel ◽  
Action Potentials ◽  
Cardiac Electrophysiology ◽  
Current Knowledge ◽  
Animal Experiments ◽  
Cardiac Cells ◽  
Cellular Mechanisms ◽  
Electrophysiological Properties ◽  
Channel Expression ◽  
Ionic Mechanisms

Cardiac arrhythmias are among the leading causes of mortality. They often arise from alterations in the electrophysiological properties of cardiac cells, and their underlying ionic mechanisms. It is therefore critical to further unravel the patho-physiology of the ionic basis of human cardiac electrophysiology in health and disease. In the first part of this review, current knowledge on the differences in ion channel expression and properties of the ionic processes that determine the morphology and properties of cardiac action potentials and calcium dynamics from cardiomyocytes in different regions of the heart are described. Then the cellular mechanisms promoting arrhythmias in congenital or acquired conditions of ion channel function (electrical remodelling) are discussed. The focus is human relevant findings obtained with clinical, experimental and computational studies, given that interspecies differences make the extrapolation from animal experiments to the human clinical settings difficult. Deepening the understanding of the diverse patholophysiology of human cellular electrophysiology will help developing novel and effective antiarrhythmic strategies for specific subpopulations and disease conditions.

Cell-specific mathematical models of cardiac electrophysiology

2016 ◽  
Vol 81 ◽  
pp. 343
Author(s):  
Ross Johnstone ◽  
Rémi Bardenet ◽  
Teun de Boer ◽  
David Gavaghan ◽  
Mark Davies ◽  
...  
Keyword(s):  
Mathematical Models ◽  
Cardiac Electrophysiology

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

2010 ◽  
Vol 1 (1) ◽  
pp. 101-116 ◽  
Author(s):  
Alan P. Benson ◽  
Olivier Bernus ◽  
Hans Dierckx ◽  
Stephen H. Gilbert ◽  
John P. Greenwood ◽  
...  
Keyword(s):  
Action Potentials ◽  
Cardiac Electrophysiology ◽  
Computational Models ◽  
Diffusion Tensor ◽  
Reaction Diffusion ◽  
Tissue Architecture ◽  
Conduction Velocities ◽  
Cardiac Geometry ◽  
Orientation Distributions ◽  
Spatio Temporal

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 λ 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 λ 2 is significantly greater than λ 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.

Mathematical models of action potentials in the periphery and center of the rabbit sinoatrial node

2000 ◽  
Vol 279 (1) ◽  
pp. H397-H421 ◽  
Author(s):  
H. Zhang ◽  
A. V. Holden ◽  
I. Kodama ◽  
H. Honjo ◽  
M. Lei ◽  
...  
Keyword(s):  
Action Potential ◽  
Mathematical Models ◽  
Action Potentials ◽  
Phase 1 ◽  
Outward Current ◽  
Transient Outward Current ◽  
Dimensional Model ◽  
Peripheral Cell ◽  
One Dimensional ◽  
Sa Node

Mathematical models of the action potential in the periphery and center of the rabbit sinoatrial (SA) node have been developed on the basis of published experimental data. Simulated action potentials are consistent with those recorded experimentally: the model-generated peripheral action potential has a more negative takeoff potential, faster upstroke, more positive peak value, prominent phase 1 repolarization, greater amplitude, shorter duration, and more negative maximum diastolic potential than the model-generated central action potential. In addition, the model peripheral cell shows faster pacemaking. The models behave qualitatively the same as tissue from the periphery and center of the SA node in response to block of tetrodotoxin-sensitive Na+current, L- and T-type Ca2+ currents, 4-aminopyridine-sensitive transient outward current, rapid and slow delayed rectifying K+ currents, and hyperpolarization-activated current. A one-dimensional model of a string of SA node tissue, incorporating regional heterogeneity, coupled to a string of atrial tissue has been constructed to simulate the behavior of the intact SA node. In the one-dimensional model, the spontaneous action potential initiated in the center propagates to the periphery at ∼0.06 m/s and then into the atrial muscle at 0.62 m/s.

Novel experimental results in human cardiac electrophysiology: measurement of the Purkinje fibre action potential from the undiseased human heart

2015 ◽  
Vol 93 (9) ◽  
pp. 803-810 ◽  
Author(s):  
Norbert Nagy ◽  
Tamás Szél ◽  
Norbert Jost ◽  
András Tóth ◽  
Julius Gy. Papp ◽  
...  
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Cardiac Electrophysiology ◽  
Human Heart ◽  
Expression Profiles ◽  
Purkinje Fibre ◽  
Purkinje Fibres ◽  
Repolarization Reserve ◽  
Protein Expression Profiles ◽  
First Time

Data obtained from canine cardiac electrophysiology studies are often extrapolated to the human heart. However, it has been previously demonstrated that because of the lower density of its K+ currents, the human ventricular action potential has a less extensive repolarization reserve. Since the relevance of canine data to the human heart has not yet been fully clarified, the aim of the present study was to determine for the first time the action potentials of undiseased human Purkinje fibres (PFs) and to compare them directly with those of dog PFs. All measurements were performed at 37 °C using the conventional microelectrode technique. At a stimulation rate of 1 Hz, the plateau potential of human PFs is more positive (8.0 ± 1.8 vs 8.6 ± 3.4 mV, n = 7), while the amplitude of the spike is less pronounced. The maximal rate of depolarization is significantly lower in human PKs than in canine PFs (406.7 ± 62 vs 643 ± 36 V/s, respectively, n = 7). We assume that the appreciable difference in the protein expression profiles of the 2 species may underlie these important disparities. Therefore, caution is advised when canine PF data are extrapolated to humans, and further experiments are required to investigate the characteristics of human PF repolarization and its possible role in arrhythmogenesis.

scholarly journals A Complete and Low-Cost Cardiac Optical Mapping System in Translational Animal Models

2021 ◽  
Vol 12 ◽  
Author(s):  
Manuel Marina-Breysse ◽  
Alba García-Escolano ◽  
Joaquín Vila-García ◽  
Gabriel Reale-Nosei ◽  
José M. Alfonso-Almazán ◽  
...  
Keyword(s):  
Action Potentials ◽  
Cardiac Electrophysiology ◽  
High Speed ◽  
Optical Mapping ◽  
Low Cost ◽  
Cytosolic Calcium ◽  
Calcium Transients ◽  
Spatiotemporal Resolution ◽  
Mapping System ◽  
Computer Scientists

Clinicians, biologists, physicists, engineers, and computer scientists are coming together to better understand heart disease, which is currently the leading cause of death globally. Optical mapping, a high-speed fluorescence imaging technique that visualizes and measures key cardiac parameters such as action potentials, cytosolic calcium transients, and fibrillation dynamics, is a core research tool that has arisen from such interdisciplinary collaborations. In an effort to broaden its use, especially among clinical scientists and students, we developed a complete and low-cost optical mapping system, including a constant-flow Langendorff perfusion system, which minimizes the economic threshold to widespread use of this powerful tool in cardiac electrophysiology research. The system described here provides high spatiotemporal resolution data about action potentials, intracellular calcium transients and fibrillation wave dynamics in isolated Langendorff-perfused hearts (pigs and rabbits), relevant for translational research. All system components and software elements are fully disclosed with the aim of increasing the use of this affordable and highly versatile tool among clinicians, basic scientists and students wishing to tackle their own research questions with their own customizable systems.

Abstract P396: Noncanonical Wnt5a Increases QT Interval And Susceptibility To Ventricular Arrhythmias

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Jerry Wang ◽  
Aizhu Lu ◽  
Ying Xia ◽  
Hongwei Wang ◽  
Cagla Cimenci ◽  
...  
Keyword(s):  
Heart Failure ◽  
Action Potentials ◽  
Qt Interval ◽  
Ventricular Arrhythmias ◽  
Cardiac Electrophysiology ◽  
Critical Role ◽  
Left Ventricular ◽  
Patch Clamp Recording ◽  
Surface Ecg ◽  
Patients With Heart Failure

Background: Wnt signaling plays a critical role in both embryonic cardiogenesis and cardiac remodeling in adult heart disease. We have previously demonstrated that the canonical Wnt/β-catenin pathway inhibits cardiac sodium current, but it remains unclear whether the noncanonical Wnt pathway affects cardiac electrophysiology. Methods and Results: Western blot analysis of ventricular tissues from patients with heart failure (n=6) demonstrated a 2.3x fold increase (p<0.01) in the protein level of Wnt5a, a noncanonical Wnt ligand, as compared to healthy ventricular tissues (n=5). To investigate if Wnt5a affects cardiac electrophysiology, adenovirus expressing Wnt5a and mCherry (Ad-Wnt5a) or control adenovirus expressing mCherry only (Ad-mCherry) was injected into the left ventricular free wall of adult rat hearts. At 4-5 days after virus injection, surface ECG revealed increased QT interval (p<0.01) in Ad-Wn5a-injected rats (90.1±2.3 ms n=7, vs 72.3±2.0 ms in control Ad-mCherry rats n=7). In addition, ventricular tachycardia was induced by programmed electrical stimulation in 92% (11/12) Ad-Wnt5a hearts, but only in 22% (2/9) control Ad-mCherry hearts (p<0.01). Patch-clamp recording of isolated single ventricular myocytes demonstrated that Ad-Wnt5a myocytes exhibited marked prolongation of action potential duration (APD 90 : 273±77ms, n=5) as compared to control cells (42±12 ms, n=7, p<0.05). In addition, the prolonged action potentials in Ad-Wnt5a myocytes were associated with frequent early afterdepolarizations and delayed afterdepolarizations, two mechanisms for triggered ventricular arrhythmias. Conclusion: Wnt5a is increased in the myocardium of patients with heart failure. Viral expression of Wnt5a in rat ventricular tissue increases QT interval and ventricular arrhythmia susceptibility, which is associated with prolongation of action potentials in cardiomyocytes. This may be an important target for future therapies.

Basic Cardiac Electrophysiology

2013 ◽  
pp. 171-190
Author(s):  
Hon-Chi Lee ◽  
Arshad Jahangir
Keyword(s):  
Ion Channels ◽  
Cardiac Arrhythmias ◽  
Action Potentials ◽  
Cardiac Electrophysiology ◽  
Structure And Function ◽  
Learning Objectives ◽  
Cardiac Ion Channels ◽  
Cardiac Action ◽  
And Function

The learning objectives of this chapter are to review some basic electrophysiologic concepts that are useful for the clinician. These include 1) the structure and function of cardiac ion channels; 2) the role of ion channels in the generation of cardiac action potentials; 3) the mechanisms of cardiac arrhythmias; and 4) inherited and acquired channelopathies.

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