35 research outputs found
Chaste: an open source C++ library for computational physiology and biology
Chaste - Cancer, Heart And Soft Tissue Environment - is an open source C++ library for the computational simulation of mathematical models developed for physiology and biology. Code development has been driven by two initial applications: cardiac electrophysiology and cancer development. A large number of cardiac electrophysiology studies have been enabled and performed, including high performance computational investigations of defibrillation on realistic human cardiac geometries. New models for the initiation and growth of tumours have been developed. In particular, cell-based simulations have provided novel insight into the role of stem cells in the colorectal crypt. Chaste is constantly evolving and is now being applied to a far wider range of problems. The code provides modules for handling common scientific computing components, such as meshes and solvers for ordinary and partial differential equations (ODEs/PDEs). Re-use of these components avoids the need for researchers to "re-invent the wheel" with each new project, accelerating the rate of progress in new applications. Chaste is developed using industrially-derived techniques, in particular test-driven development, to ensure code quality, re-use and reliability. In this article we provide examples that illustrate the types of problems Chaste can be used to solve, which can be run on a desktop computer. We highlight some scientific studies that have used or are using Chaste, and the insights they have provided. The source code, both for specific releases and the development version, is available to download under an open source Berkeley Software Distribution (BSD) licence at http://www.cs.ox.ac.uk/chaste, together with details of a mailing list and links to documentation and tutorials
3D finite element electrical model of larval zebrafish ECG signals
Assessment of heart function in zebrafish larvae using electrocardiography (ECG) is a potentially useful tool in developing cardiac treatments and the assessment of drug therapies. In order to better understand how a measured ECG waveform is related to the structure of the heart, its position within the larva and the position of the electrodes, a 3D model of a 3 days post fertilisation (dpf) larval zebrafish was developed to simulate cardiac electrical activity and investigate the voltage distribution throughout the body. The geometry consisted of two main components; the zebrafish body was modelled as a homogeneous volume, while the heart was split into five distinct regions (sinoatrial region, atrial wall, atrioventricular band, ventricular wall and heart chambers). Similarly, the electrical model consisted of two parts with the body described by Laplace’s equation and the heart using a bidomain ionic model based upon the Fitzhugh-Nagumo equations. Each region of the heart was differentiated by action potential (AP) parameters and activation wave conduction velocities, which were fitted and scaled based on previously published experimental results. ECG measurements in vivo at different electrode recording positions were then compared to the model results. The model was able to simulate action potentials, wave propagation and all the major features (P wave, R wave, T wave) of the ECG, as well as polarity of the peaks observed at each position. This model was based upon our current understanding of the structure of the normal zebrafish larval heart. Further development would enable us to incorporate features associated with the diseased heart and hence assist in the interpretation of larval zebrafish ECGs in these conditions
Effects of amiodarone on short QT syndrome variant 3 in human ventricles: a simulation study.
Background Short QT syndrome (SQTS) is a newly identified clinical disorder associated with atrial and/or ventricular arrhythmias and increased risk of sudden cardiac death (SCD). The SQTS variant 3 is linked to D172N mutation to the KCNJ2 gene that causes a gain-of-function to the inward rectifier potassium channel current (I K1), which shortens the ventricular action potential duration (APD) and effective refractory period (ERP). Pro-arrhythmogenic effects of SQTS have been characterized, but less is known about the possible pharmacological treatment of SQTS. Therefore, in this study, we used computational modeling to assess the effects of amiodarone, class III anti-arrhythmic agent, on human ventricular electrophysiology in SQT3.
Methods The ten Tusscher et al. model for the human ventricular action potentials (APs) was modified to incorporate I K1 formulations based on experimental data of Kir2.1 channels (including WT, WT-D172N and D172N conditions). The modified cell model was then implemented to construct one-dimensional (1D) and 2D tissue models. The blocking effects of amiodarone on ionic currents were modeled using IC50 and Hill coefficient values from literatures. Effects of amiodarone on APD, ERP and pseudo-ECG traces were computed. Effects of the drug on the temporal and spatial vulnerability of ventricular tissue to genesis and maintenance of re-entry were measured, as well as on the dynamic behavior of re-entry.
Results Amiodarone prolonged the ventricular cell APD and decreased the maximal voltage heterogeneity (δV) among three difference cells types across transmural ventricular wall, leading to a decreased transmural heterogeneity of APD along a 1D model of ventricular transmural strand. Amiodarone increased cellular ERP, prolonged QT interval and decreased the T-wave amplitude. It reduced tissue’s temporal susceptibility to the initiation of re-entry and increased the minimum substrate size necessary to sustain re-entry in the 2D tissue.
Conclusions At the therapeutic-relevant concentration of amiodarone, the APD and ERP at the single cell level were increased significantly. The QT interval in pseudo-ECG was prolonged and the re-entry in tissue was prevented. This study provides further evidence that amiodarone may be a potential pharmacological agent for preventing arrhythmogenesis for SQT3 patients
In silico assessment of the effects of quinidine, disopyramide and E-4031 on short QT syndrome variant 1 in the human ventricles.
Aims Short QT syndrome (SQTS) is an inherited disorder associated with abnormally abbreviated QT intervals and an increased incidence of atrial and ventricular arrhythmias. SQT1 variant (linked to the rapid delayed rectifier potassium channel current, IKr) of SQTS, results from an inactivation-attenuated, gain-of-function mutation (N588K) in the KCNH2-encoded potassium channels. Pro-arrhythmogenic effects of SQT1 have been well characterized, but less is known about the possible pharmacological antiarrhythmic treatment of SQT1. Therefore, this study aimed to assess the potential effects of E-4031, disopyramide and quinidine on SQT1 using a mathematical model of human ventricular electrophysiology.
Methods The ten Tusscher et al. biophysically detailed model of the human ventricular action potential (AP) was modified to incorporate IKr Markov chain (MC) formulations based on experimental data of the kinetics of the N588K mutation of the KCNH2-encoded subunit of the IKr channels. The modified ventricular cell model was then integrated into one-dimensional (1D) strand, 2D regular and realistic tissues with transmural heterogeneities. The channel-blocking effect of the drugs on ion currents in healthy and SQT1 cells was modeled using half-maximal inhibitory concentration (IC50) and Hill coefficient (nH) values from literatures. Effects of drugs on cell AP duration (APD), effective refractory period (ERP) and pseudo-ECG traces were calculated. Effects of drugs on the ventricular temporal and spatial vulnerability to re-entrant excitation waves were measured. Re-entry was simulated in both 2D regular and realistic ventricular tissue.
Results At the single cell level, the drugs E-4031 and disopyramide had hardly noticeable effects on the ventricular cell APD at 90% repolarization (APD90), whereas quinidine caused a significant prolongation of APD90. Quinidine prolonged and decreased the maximal transmural AP heterogeneity (δV); this led to the decreased transmural heterogeneity of APD across the 1D strand. Quinidine caused QT prolongation and a decrease in the T-wave amplitude, and increased ERP and decreased temporal susceptibility of the tissue to the initiation of re-entry and increased the minimum substrate size necessary to prevent re-entry in the 2D regular model, and further terminated re-entrant waves in the 2D realistic model. Quinidine exhibited significantly better therapeutic effects on SQT1 than E-4031 and disopyramide.
Conclusions The simulated pharmacological actions of quinidine exhibited antiarrhythmic effects on SQT1. This study substantiates a causal link between quinidine and QT interval prolongation in SQT1 and suggests that quinidine may be a potential pharmacological agent for treating SQT1 patients
Characterisation of friction at the tool–chip interface for orthogonal cutting of Ti-6Al-4V alloy
From intracardiac electrograms to electrocardiograms: Models and metamodels
International audienceWe consider the problem of building a standard electrocardiogram (ECG) from the electrical potential provided by a pacemaker in a few points of the heart (electrogram). We use a 3D mathematical model of the heart and the torso electrical activity, able to generate "computational ECG", and a "metamodel" based on a kernel ridge regression. The input of the metamodel is the electrogram, its output is the ECG. The 3D model is used to train and test the metamodel. We illustrate the performance of the proposed strategy on simulated bundle branch blocks of various severities and a few clinical dat
Identification of friction and heat partition model at the tool-chip-workpiece interfaces in dry cutting of an inconel 718 alloy with cbn and coated carbide tools
This paper aims at characterizing the frictional behaviour at the cutting tool-workmaterial interface during the dry machining of a Inconel 718 in its aged state with various coated carbide tools and c-BN tools. A specially designed open tribometer has been used to characterize friction coefficient, heat partition coefficient under extreme conditions corresponding to the ones occurring in cutting. The tribometer provides the evolution of the apparent friction coefficient and of the heat partition coefficient for a large range of sliding velocity and contact pressure. It has been shown that friction coefficient as well as heat partition coefficient decrease with sliding velocity or contact pressure. A threshold effect of the contact pressure has been highlighted. On the contrary, any sensitivity to coatings deposited on carbide has been observed, whereas c-BN leads to very low friction coefficients.W pracy określono charakterystykę tarciowego zachowania się strefy kontaktu wiór-ostrze obrabianego w toczeniu na sucho nadstopu Inconel 718 po starzeniu narzędziami wykonanymi z różnych gatunków węglików spiekanych z naniesionymi powłokami i polikrystalicznego CBN. Zaprojektowano i wykonano
tribometr do wyznaczania wartości współczynnika tarcia i współczynnika podziału ciepła. Badania prowadzono w warunkach ekstremalnych zbliżonych do występujących w procesie skrawania na sucho. Tribometr umożliwia pomiary w czasie wartości pozornego współczynnika tarcia i przepływ
ciepła dla dużego zakresu wartości prędkości skrawania i nacisku normalnego. Wykazano, że zarówno współczynnik tarcia, jak i podziału ciepła zmniejszają się przy wzroście prędkości i siły normalnej skrawania. Określono graniczny efekt nacisku kontaktowego. Nie stwierdzono wpływu rodzaju powłoki na ostrzu z węglika spiekanego na wartość współczynnika tarcia. Natomiast skrawanie narzędziami z ostrzem p-CBN prowadzi do uzyskania bardzo małej wartości współczynnika tarcia
Identyfikacja tarcia i model podziału ciepła w strefie kontaktu wiór-ostrze-materiał obrabiany w toczeniu na sucho nadstopu Inconel 718 narzędziami z CBN i węglików spiekanych z naniesionymi powłokami
This paper aims at characterizing the frictional behaviour at the cutting tool-workmaterial interface during the dry machining of a Inconel 718 in its aged state with various coated carbide tools and c-BN tools. A specially designed open tribometer has been used to characterize friction coefficient, heat partition coefficient under extreme conditions corresponding to the ones occurring in cutting. The tribometer provides the evolution of the apparent friction coefficient and of the heat partition coefficient for a large range of sliding velocity and contact pressure. It has been shown that friction coefficient as well as heat partition coefficient decrease with sliding velocity or contact pressure. A threshold effect of the contact pressure has been highlighted. On the contrary, any sensitivity to coatings deposited on carbide has been observed, whereas c-BN leads to very low friction coefficients.W pracy określono charakterystykę tarciowego zachowania się strefy kontaktu wiór-ostrze obrabianego w toczeniu na sucho nadstopu Inconel 718 po starzeniu narzędziami wykonanymi z różnych gatunków węglików spiekanych z naniesionymi powłokami i polikrystalicznego CBN. Zaprojektowano i wykonano
tribometr do wyznaczania wartości współczynnika tarcia i współczynnika podziału ciepła. Badania prowadzono w warunkach ekstremalnych zbliżonych do występujących w procesie skrawania na sucho. Tribometr umożliwia pomiary w czasie wartości pozornego współczynnika tarcia i przepływ
ciepła dla dużego zakresu wartości prędkości skrawania i nacisku normalnego. Wykazano, że zarówno współczynnik tarcia, jak i podziału ciepła zmniejszają się przy wzroście prędkości i siły normalnej skrawania. Określono graniczny efekt nacisku kontaktowego. Nie stwierdzono wpływu rodzaju powłoki na ostrzu z węglika spiekanego na wartość współczynnika tarcia. Natomiast skrawanie narzędziami z ostrzem p-CBN prowadzi do uzyskania bardzo małej wartości współczynnika tarcia