scholarly journals Antenatal architecture and activity of the human heart

2013 ◽  
Vol 3 (2) ◽  
pp. 20120065 ◽  
Author(s):  
Eleftheria Pervolaraki ◽  
Richard A. Anderson ◽  
Alan P. Benson ◽  
Barrie Hayes-Gill ◽  
Arun V. Holden ◽  
...  
Keyword(s):  
Computational Models ◽  
Cardiac Tissue ◽  
Molecular Mapping ◽  
Diffusion Tensor ◽  
Foetal Heart ◽  
Qt Intervals ◽  
Ventricular Cells ◽  
Adult Cell ◽  
Cardiac Geometry ◽  
Human Foetal Heart

We construct the components for a family of computational models of the electrophysiology of the human foetal heart from 60 days gestational age (DGA) to full term. This requires both cell excitation models that reconstruct the myocyte action potentials, and datasets of cardiac geometry and architecture. Fast low-angle shot and diffusion tensor magnetic resonance imaging (DT-MRI) of foetal hearts provides cardiac geometry with voxel resolution of approximately 100 μm. DT-MRI measures the relative diffusion of protons and provides a measure of the average intravoxel myocyte orientation, and the orientation of any higher order orthotropic organization of the tissue. Such orthotropic organization in the adult mammalian heart has been identified with myocardial sheets and cleavage planes between them. During gestation, the architecture of the human ventricular wall changes from being irregular and isotropic at 100 DGA to an anisotropic and orthotropic architecture by 140 DGA, when it has the smooth, approximately 120° transmural change in myocyte orientation that is characteristic of the adult mammalian ventricle. The DT obtained from DT-MRI provides the conductivity tensor that determines the spread of potential within computational models of cardiac tissue electrophysiology. The foetal electrocardiogram (fECG) can be recorded from approximately 60 DGA, and RR, PR and QT intervals between the P, R, Q and T waves of the fECG can be extracted by averaging from approximately 90 DGA. The RR intervals provide a measure of the pacemaker rate, the QT intervals an index of ventricular action potential duration, and its rate-dependence, and so these intervals constrain and inform models of cell electrophysiology. The parameters of models of adult human sinostrial node and ventricular cells that are based on adult cell electrophysiology and tissue molecular mapping have been modified to construct preliminary models of foetal cell electrophysiology, which reproduce these intervals from fECG recordings. The PR and QR intervals provide an index of conduction times, and hence propagation velocities (approx. 1–10 cm s −1 , increasing during gestation) and so inform models of tissue electrophysiology. Although the developing foetal heart is small and the cells are weakly coupled, it can support potentially lethal re-entrant arrhythmia.

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.

Connexin expression in the developing mouse heart and human foetal heart

2001 ◽  
Vol 33 (6) ◽  
pp. A23
Author(s):  
Steven R. Coppen ◽  
Riyaz A. Kaba ◽  
Robert G. Gourdie ◽  
Jeremy N. Skepper ◽  
Suzy Elneil ◽  
...  
Keyword(s):  
Mouse Heart ◽  
Foetal Heart ◽  
Connexin Expression ◽  
Human Foetal Heart

scholarly journals Anisotropic Cardiac Conduction

2020 ◽  
Vol 9 (4) ◽  
pp. 202-210
Author(s):  
Irum Kotadia ◽  
John Whitaker ◽  
Caroline Roney ◽  
Steven Niederer ◽  
Mark O’Neill ◽  
...  
Keyword(s):  
Gap Junction ◽  
Cardiac Tissue ◽  
Diffusion Tensor ◽  
Interstitial Fibrosis ◽  
Cardiac Conduction ◽  
Principal Mechanism ◽  
Disease States ◽  
And Function ◽  
Anisotropic Conduction

Anisotropy is the property of directional dependence. In cardiac tissue, conduction velocity is anisotropic and its orientation is determined by myocyte direction. Cell shape and size, excitability, myocardial fibrosis, gap junction distribution and function are all considered to contribute to anisotropic conduction. In disease states, anisotropic conduction may be enhanced, and is implicated, in the genesis of pathological arrhythmias. The principal mechanism responsible for enhanced anisotropy in disease remains uncertain. Possible contributors include changes in cellular excitability, changes in gap junction distribution or function and cellular uncoupling through interstitial fibrosis. It has recently been demonstrated that myocyte orientation may be identified using diffusion tensor magnetic resonance imaging in explanted hearts, and multisite pacing protocols have been proposed to estimate myocyte orientation and anisotropic conduction in vivo. These tools have the potential to contribute to the understanding of the role of myocyte disarray and anisotropic conduction in arrhythmic states.

scholarly journals Multi-scale dynamic mean field model (MDMF) relates resting-state brain dynamics with local cortical excitatory–inhibitory neurotransmitter homeostasis

2021 ◽  
pp. 1-55
Author(s):  
Amit Naskar ◽  
Anirudh Vattikonda ◽  
Gustavo Deco ◽  
Dipanjan Roy ◽  
Arpan Banerjee
Keyword(s):  
Resting State ◽  
Computational Models ◽  
Field Model ◽  
Diffusion Tensor ◽  
Brain Activity ◽  
Mean Field ◽  
Clustering Coefficient ◽  
Brain Dynamics ◽  
Mean Field Model ◽  
Multi Scale

Abstract Previous computational models have related spontaneous resting-state brain activity with local excitatory−inhibitory balance in neuronal populations. However, how underlying neurotransmitter kinetics associated with E-I balance governs resting state spontaneous brain dynamics remains unknown. Understanding the mechanisms by virtue of which fluctuations in neurotransmitter concentrations, a hallmark of a variety of clinical conditions relate to functional brain activity is of critical importance. We propose a multi-scale dynamic mean field model (MDMF) – a system of coupled differential equations for capturing the synaptic gating dynamics in excitatory and inhibitory neural populations as a function of neurotransmitter kinetics. Individual brain regions are modelled as population of MDMF and are connected by realistic connection topologies estimated from Diffusion Tensor Imaging data. First, MDMF successfully predicts resting-state functionalconnectivity. Second, our results show that optimal range of glutamate and GABA neurotransmitter concentrations subserve as the dynamic working point of the brain, that is, the state of heightened metastability observed in empirical blood-oxygen-level dependent signals. Third, for predictive validity the network measures of segregation (modularity and clustering coefficient) and integration (global efficiency and characteristic path length) from existing healthy and pathological brain network studies could be captured by simulated functional connectivity from MDMF model.

The Use of a Cellular Strain Injury Criterion and Diffusion Tensor Imaging in a Computational Model of Traumatic Brain Injury

2010 ◽  
Author(s):  
Rika M. Wright ◽  
K. T. Ramesh
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mechanical Loading ◽  
Computational Models ◽  
Diffusion Tensor ◽  
Diffuse Axonal Injury ◽  
Element Model ◽  
Cellular Level ◽  
Cellular Injury ◽  
Injury Mechanisms

With the increase in the number of soldiers sustaining traumatic brain injury from military incidents and the recent attention on sports related traumatic brain injury, there has been a focused effort to develop preventative and treatment methods for traumatic brain injury (TBI). Traumatic brain injury is caused by mechanical loading to the head, such as from impacts, sudden accelerations, or blast loading, and the pathology can range from focal damage in the brain to widespread diffuse injury [1]. In this study, we investigate the injury mechanisms of diffuse axonal injury (DAI), which accounts for the second largest percentage of deaths due to brain trauma [2]. DAI is caused by sudden inertial loads to the head, and it is characterized by damage to neural axons. Despite the extensive research on DAI, the coupling between the mechanical loading to the head and the damage at the cellular level is still poorly understood. Unlike previous computational models that use macroscopic stress and strain measures to determine injury, a cellular injury criterion is used in this work as numerous studies have shown that cellular strain can be related to the functional damage of neurons. The effectiveness of using this cellular injury criterion to predict damage in a finite element model of DAI is investigated.

A computationally efficient electrophysiological model of human ventricular cells

2002 ◽  
Vol 282 (6) ◽  
pp. H2296-H2308 ◽  
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.

scholarly journals Cardiac alternans induced by fibroblast-myocyte coupling: mechanistic insights from computational models

2009 ◽  
Vol 297 (2) ◽  
pp. H775-H784 ◽  
Author(s):  
Yuanfang Xie ◽  
Alan Garfinkel ◽  
James N. Weiss ◽  
Zhilin Qu
Keyword(s):  
Action Potential ◽  
Computational Models ◽  
Cardiac Tissue ◽  
Experimental Studies ◽  
Outward Current ◽  
Transient Outward Current ◽  
Two Dimensional ◽  
Background Current ◽  
Cardiac Alternans ◽  
Main Components

Recent experimental studies have shown that fibroblasts can electrotonically couple to myocytes via gap junctions. In this study, we investigated how this coupling affects action potential and intracellular calcium (Cai) cycling dynamics in simulated fibroblast-myocyte pairs and in two-dimensional tissue with random fibroblast insertions. We show that a fibroblast coupled with a myocyte generates a gap junction current flowing to the myocyte with two main components: an early pulse of transient outward current, similar to the fast transient outward current, and a later background current during the repolarizing phase. Depending on the relative prominence of the two components, fibroblast-myoycte coupling can 1) prolong or shorten action potential duration (APD), 2) promote or suppress APD alternans due to steep APD restitution (voltage driven) and also result in a novel mechanism of APD alternans at slow heart rates, 3) promote Cai-driven alternans and electromechanically discordant alternans, and 4) promote spatially discordant alternans by two mechanisms: by altering conduction velocity restitution and by heterogeneous fibroblast distribution causing electromechanically concordant and discordant alternans in different regions of the tissue. Thus, through their coupling with myocytes, fibroblasts alter repolarization and Cai cycling alternans at both the cellular and tissue scales, which may play important roles in arrhythmogenesis in diseased cardiac tissue with fibrosis.

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