@article{, abstract = "Chaste (‘Cancer, heart and soft-tissue environment’) is a software library and a set of test suites for computational simulations in the domain of biology. Current functionality has arisen from modelling in the fields of cancer, cardiac physiology and soft-tissue mechanics. It is released under the LGPL 2.1 licence. Chaste has been developed using agile programming methods. The project began in 2005 when it was reasoned that the modelling of a variety of physiological phenomena required both a generic mathematical modelling framework, and a generic computational/simulation framework. The Chaste project evolved from the Integrative Biology (IB) e-Science Project, an inter-institutional project aimed at developing a suitable IT infrastructure to support physiome-level computational modelling, with a primary focus on cardiac and cancer modelling.", author = "J Pitt-Francis, P Pathmanathan, MO Bernabeu, R Bordas, J Cooper, AG Fletcher, GR Mirams, P Murray, JM Osborne, A Walter, SJ Chapman, A Garny, I van Leeuwen, PK Maini, B Rodríguez, SL Waters, JP Whiteley, HM Byrne and DJ Gavaghan", journal = "Computer Physics Communications", title = "Chaste: A test-driven approach to software development for biological modelling", volume = "(in press)", year = "2009", } @article{Plank2009, author = "Plank G, Burton RAB, Hales P, Bishop MJ, Mansoori T, Bernabeu MO, Garny A, Prassl AJ, Bollensdorff C, Mason F, Mahmood F, Rodriguez B, Grau V, Schneider J, Gavaghan DJ, Kohl P", journal = "Phil Trans Roy Soc", title = "Generation of histo-anatomically representative models of the individual heart: tools and application.", year = "2009", } @article{ChasteCPC09, author = "Pitt-Francis J, Pathmanathan P, Bernabeu MO, Bordas R, Cooper J, Fletcher AG, Mirams GR, Murray P, Osbourne JM, Walter A, Chapman J, Garny A, van Leeuwen IM, Maini PK; Rodriguez B, Waters SL, Whiteley JP, Byrne HM, Gavaghan DJ", journal = "Computer Physics Communications", title = "Chaste: a test-driven approach to software development for biological modelling", year = "2009", } @article{Lucia09, author = "Romero L, Pueyo E, Fink M, Rodriguez B", journal = "American Journal of Physiology", title = "Impact of ionic current variability on human ventricular cellular electrophysiology", year = "2009", } @article{Chaste2, author = "Bernabeu MO, Bordas R, Pathmanathan P, Pitt-Francis J, Cooper J, Garny A, Gavaghan DJ, Rodriguez B, Southern JA, Whiteley JP", doi = "10.1098/rsta.2008.0309", journal = "Phil Trans Roy Soc (A)", month = "May", number = "1895", pages = "1907-1930", title = "Chaste: Incorporating a Novel Multiscale Spatial and Temporal Algorithm into a Large Scale Open Source Library", volume = "367", year = "2009", } @article{EJPS08, author = "Brennan T, Fink M, Rodriguez B", journal = "European Journal of Pharmaceutical Sciences", title = "Multiscale modelling of drug-induced effects on cardiac electrophysiological activity", year = "2009", } @article{BishopPhysicaD, author = "Bishop MJ, Bub G, Garny A, Gavaghan D, Rodriguez B", journal = "Physica D", title = "An investigation into the role of the optical detection set-up in the recording of cardiac optical mapping signals: a Monte Carlo simulation study.", year = "2009", } Warning - the bibtex entry below may be invalid: Missing 'journal' field @article{Plotkowiack, author = "Michal Plotkowiak, Blanca Rodriguez, Gernot Plank, Jurgen E. Schneider, David Gavaghan, Peter Kohl, Vicente Grau", title = "High Performance Computer Simulations of Cardiac Electrical Function based on MRI datasets", year = "2008", } @article{Chaste_paper, author = "Joe Pitt-Francis, Miguel O. Bernabeu, Jonathan Cooper, Alan Garny, Lee Momtahan, James Osborne, Pras Pathmanathan, Blanca Rodriguez, Jonathan P. Whiteley, David J. Gavaghan", doi = "10.1098/rsta.2008.0096", journal = "Phil Trans Roy Soc A", number = "1878", pages = "3111-3136", title = "Chaste: using agile programming techniques to develop computational biology software", volume = "366", year = "2008", } @article{xiao08, author = "Jie X, Rodriguez B, de Groot J, Coronel R, Trayanova N", journal = "Heart Rhythm", title = "Reentry in Survived Subepicardium Coupled to Depolarized and Inexcitable Midmyocardium: Insights into Arrhythmogenesis in Ischemia Phase 1B", year = "2008", } @article{TransmuralHeterogeneities, abstract = "Aims Studies of arrhythmogenesis during ischemia have focused primarily on reentrant mechanisms manifested on the epicardial surface. The goal of this study was to use a physiologically-accurate model of acute regional ischemia phase 1A to determine the contribution of ischaemia-induced transmural electrophysiological heterogeneities to arrhythmogenesis following left anterior descending artery occlusion. Methods and results A slice through a geometrical model of the rabbit ventricles was extracted and a model of regional ischaemia developed. The model included a central ischaemic zone incorporating transmural gradients of I(K(ATP)) activation and [K(+)](o), surrounded by ischaemic border zones (BZs), with the degree of ischaemic effects varied to represent progression of ischaemia 2-10 min post-occlusion. Premature stimulation was applied over a range of coupling intervals to induce re-entry. The presence of ischaemic BZs and a transmural gradient in I(K(ATP)) activation provided the substrate for re-entrant arrhythmias. Increased dispersion of refractoriness and conduction velocity in the BZs with time post-occlusion led to a progressive increase in arrhythmogenesis. In the absence of a transmural gradient of I(K(ATP)) activation, re-entry was rarely sustained. Conclusion Knowledge of the mechanism by which specific electrophysiological heterogeneities underlie arrhythmogenesis during acute ischaemia could be useful in developing preventative treatments for patients at risk of coronary vascular disease.", author = "Tice, BM and Rodr{\'i}guez, B and Eason, J and Trayanova, N", journal = "Europace", pages = "vi46-vi58", title = "Mechanistic investigation into the arrhythmogenic role of transmural heterogeneities in regional ischaemia phase 1A.", volume = "9 Suppl 6", year = "2007", } @article{RoleTransmural, abstract = "Transmural electrophysiological heterogeneities have been shown to contribute to arrhythmia induction in the heart; however, their role in defibrillation failure has never been examined. The goal of this study is to investigate how transmural heterogeneities in ionic currents and gap-junctional coupling contribute to arrhythmia generation following defibrillation strength shocks. This study used a 3D anatomically realistic bidomain model of the rabbit ventricles. Transmural heterogeneity in ionic currents and reduced sub-epicardial intercellular coupling were incorporated based on experimental data. The ventricles were paced apically, and truncated-exponential monophasic shocks of varying strength and timing were applied via large external electrodes. Simulations demonstrate that inclusion of transmural heterogeneity in ionic currents results in an increase in vulnerability to shocks, reflected in the increased upper limit of vulnerability, ULV, and the enlarged vulnerable window, VW. These changes in vulnerability stem from increased post-shock dispersion in repolarisation as it increases the likelihood of establishment of re-entrant circuits. In contrast, reduced sub-epicardial coupling results in decrease in both ULV and VW. This decrease is caused by altered virtual electrode polarisation around the region of sub-epicardal uncoupling, and specifically, by the increase in (1) the amount of positively polarised myocardium at shock-end and (2) the spatial extent of post-shock wavefronts.", author = "Maharaj, T and Blake, R and Trayanova, N and Gavaghan, D and Rodr{\'i}guez, B", journal = "Prog Biophys Mol Biol", title = "The role of transmural ventricular heterogeneities in cardiac vulnerability to electric shocks.", year = "2007", } @article{RolePhotonScattering, abstract = "Optical mapping of arrhythmias and defibrillation provides important insights; however, a limitation of the technique is signal distortion due to photon scattering. The goal of this experimental/simulation study is to investigate the role of three-dimensional photon scattering in optical signal distortion during ventricular tachycardia (VT) and defibrillation. A three-dimensional realistic bidomain rabbit ventricular model was combined with a model of photon transport. Shocks were applied via external electrodes to induce sustained VT, and transmembrane potentials (V(m)) were compared with synthesized optical signals (V(opt)). Fluorescent recordings were conducted in isolated rabbit hearts to validate simulation results. Results demonstrate that shock-induced membrane polarization magnitude is smaller in V(opt) and in experimental signals as compared to V(m). This is due to transduction of potentials from weakly polarized midmyocardium to the epicardium. During shock-induced reentry and in sustained VT, photon scattering, combined with complex wavefront dynamics, results in optical action potentials near a filament exhibiting i), elevated resting potential, ii), reduced amplitude relative to pacing, and iii), dual-humped morphologies. A shift of up to 4 mm in the phase singularity location was observed in V(opt) maps when compared to V(m). This combined experimental/simulation study provides an interpretation of optical recordings during VT and defibrillation.", author = "Bishop, MJ and Rodr{\'i}guez, B and Qu, F and Efimov, IR and Gavaghan, DJ and Trayanova, NA", journal = "Biophys J", number = "10", pages = "3714-26", title = "The Role of Photon Scattering in Optical Signal Distortion during Arrhythmia and Defibrillation.", volume = "93", year = "2007", } @article{PhotonScattering, abstract = "BACKGROUND: Optical mapping is a widely used experimental tool providing high-resolution recordings of cardiac electrical activity. However, the technique is limited by signal distortion due to photon scattering in the tissue. Computational models of the fluorescence recording are capable of assessing these distortion effects, providing important insight to assist experimental data interpretation. METHODS: We present results from a new panoramic optical mapping model, which is used to assess distortion in ventricular optical mapping signals during pacing and arrhythmogenesis arising from 3-dimensional photon scattering. RESULTS/CONCLUSIONS: We demonstrate that accurate consideration of wavefront propagation within the complex ventricular structure, along with accurate representation of photon scattering in 3 dimensions, is essential to faithfully assess distortion effects arising during optical mapping. In this article, examined effects include (1) the specific morphology of the optical action potential upstroke during pacing and (2) the shift in the location of epicardial phase singularities obtained from fluorescent maps.", author = "Bishop, MJ and Gavaghan, DJ and Trayanova, NA and Rodr{\'i}guez, B", journal = "J Electrocardiol", keywords = "Animals Arrhythmias, Cardiac Body Surface Potential Mapping Computer Simulation Heart Conduction System Humans Image Interpretation, Computer-Assisted Microscopy, Fluorescence Models, Cardiovascular Photons Scattering, Radiation", number = "6 Suppl", pages = "S75-80", title = "Photon scattering effects in optical mapping of propagation and arrhythmogenesis in the heart.", volume = "40", year = "2007", } @article{Arrhythmogenesis, abstract = "The mechanisms of initiation of ventricular arrhythmias as well as those behind the complex spatiotemporal wave dynamics and its filament organization during ventricular fibrillation (VF) are the topic of intense research and debate. Mechanistic inquiry into the various mechanisms that lead to arrhythmia initiation and VF maintenance is hampered by the inability of current experimental techniques to resolve, with sufficient accuracy, electrical behavior confined to the depth of the ventricles. The objective of this article is to demonstrate that realistic 3D simulations of electrical activity in the heart are capable of bringing a new level of understanding of the mechanisms that underlie arrhythmia initiation and subsequent organization. The article does this by presenting the results of two multiscale simulation studies of ventricular electrical behavior. The first study aims to uncover the mechanisms responsible for rendering the ventricles vulnerable to electric shocks during a specific interval of time, the vulnerable window. The second study focuses on elucidating the role of electrophysiological heterogeneity, and specifically, differences in action potential duration in various ventricular structures, in VF organization. Both studies share common multiscale modeling approaches and analysis, including characterization of scroll-wave filament dynamics.", author = "Arevalo, H and Rodr{\'i}guez, B and Trayanova, N", journal = "Chaos", keywords = "Action Potentials Animals Arrhythmia Biological Clocks Computer Simulation Electric Countershock Heart Conduction System Heart Ventricles Humans Models, Cardiovascular Myocardial Contraction Oscillometry Rabbits Therapy, Computer-Assisted", number = "1", pages = "015103", title = "Arrhythmogenesis in the heart: Multiscale modeling of the effects of defibrillation shocks and the role of electrophysiological heterogeneity.", volume = "17", year = "2007", } @article{WhatWeHaveLearned, author = "Trayanova, N and Plank, G and Rodr{\'i}guez, B", journal = "Heart Rhythm", keywords = "Animals Arrhythmia Computer Simulation Electric Countershock Heart Rate Heart Ventricles Humans Models, Theoretical", number = "10", pages = "1232-5", title = "What have we learned from mathematical models of defibrillation and postshock arrhythmogenesis? Application of bidomain simulations.", volume = "3", year = "2006", } @article{ModelingCardiacIschemia, abstract = "Myocardial ischemia is one of the main causes of sudden cardiac death, with 80% of victims suffering from coronary heart disease. In acute myocardial ischemia, the obstruction of coronary flow leads to the interruption of oxygen flow, glucose, and washout in the affected tissue. Cellular metabolism is impaired and severe electrophysiological changes in ionic currents and concentrations ensue, which favor the development of lethal cardiac arrhythmias such as ventricular fibrillation. Due to the burden imposed by ischemia in our societies, a large body of research has attempted to unravel the mechanisms of initiation, sustenance, and termination of cardiac arrhythmias in acute ischemia, but the rapidity and complexity of ischemia-induced changes as well as the limitations in current experimental techniques have hampered evaluation of ischemia-induced alterations in cardiac electrical activity and understanding of the underlying mechanisms. Over the last decade, computer simulations have demonstrated the ability to provide insight, with high spatiotemporal resolution, into ischemic abnormalities in cardiac electrophysiological behavior from the ionic channel to the whole organ. This article aims to review and summarize the results of these studies and to emphasize the role of computer simulations in improving the understanding of ischemia-related arrhythmias and how to efficiently terminate them.", author = "Rodr{\'i}guez, B and Trayanova, N and Noble, D", journal = "Ann N Y Acad Sci", keywords = "Action Potentials Electrocardiography Models, Biological Myocardial Ischemia", pages = "395-414", title = "Modeling cardiac ischemia.", volume = "1080", year = "2006", } @article{DifferencesBetween, abstract = "Despite the fact that elucidating the mechanisms of cardiac vulnerability to electric shocks is crucial to understanding why defibrillation shocks fail, important aspects of cardiac vulnerability remain unknown. This research utilizes a novel anatomically based bidomain finite-element model of the rabbit ventricles to investigate the effect of shock polarity reversal on the reentrant activity induced by an external defibrillation-strength shock in the paced ventricles. The specific goal of the study is to examine how differences between left and right ventricular chamber anatomy result in differences in the types of reentrant circuits established by the shock. Truncated exponential monophasic shocks of duration 8 ms were delivered via two external electrodes at various timings. Vulnerability grids were constructed for shocks of reversed polarity (referred to as RV- or LV- when either the RV or the LV electrode is a cathode). Our results demonstrate that reversing electrode polarity from RV- to LV- changes the dominant type of post-shock reentry: it is figure-of-eight for RV- and quatrefoil for LV- shocks. Differences in secondary types of post-shock arrhythmia also occur following shock polarity reversal. These effects of polarity reversal are primarily due to the fact that the LV wall is thicker than the RV, resulting in a post-shock excitable gap that is predominantly within the LV wall for RV- shocks and in the septum for LV- shocks.", author = "Rodr{\'i}guez, B and Eason, JC and Trayanova, N", journal = "Prog Biophys Mol Biol", keywords = "Animals Arrhythmia Defibrillators Heart Ventricles Models, Cardiovascular Rabbits", number = "1-3", pages = "399-413", title = "Differences between left and right ventricular anatomy determine the types of reentrant circuits induced by an external electric shock. A rabbit heart simulation study.", volume = "90", year = "2006", } @article{MechanisticEnquiry, abstract = "The goal of this study is to investigate the mechanisms responsible for the increase in the upper limit of vulnerability (ULV; highest shock strength that induces arrhythmia) following the increase in pacing rate. To accomplish this goal, the study employs a three-dimensional bidomain finite element model of a slice through the canine ventricles. The preparation was paced eight times at a basic cycle length (BCL) of either 80 or 150ms followed by delivery of shocks of various strengths and timings. Our results demonstrate that the shock strength, which induced an arrhythmia 50% of the time, increased 20% for the faster pacing compared to the slower pacing. Analysis of the mechanisms underlying the increased vulnerability revealed that delayed post-shock activations originating in the tissue depths appear as breakthrough activations on the surfaces of the preparation following an isoelectric window (IW). However, the IW duration was consistently shorter in the faster-paced preparation. Consequently, breakthrough activations appeared on the surfaces of this preparation earlier, when the tissue was less recovered, resulting in higher probability of unidirectional block and reentry. This explains why shocks of the same strength were more likely to result in arrhythmia induction when delivered to a preparation that was rapidly paced.", author = "Bourn, DW and Maleckar, MM and Rodr{\'i}guez, B and Trayanova, NA", journal = "Philos Transact A Math Phys Eng Sci", keywords = "Action Potentials Animals Arrhythmia Biological Clocks Cardiac Pacing, Artificial Computer Simulation Heart Conduction System Heart Rate Humans Models, Cardiovascular Risk Assessment Risk Factors", number = "1843", pages = "1333-48", title = "Mechanistic enquiry into the effect of increased pacing rate on the upper limit of vulnerability.", volume = "364", year = "2006", } @article{InferenceIntramural, author = "Bishop, MJ and Rodr{\'i}guez, B and Trayanova, N and Gavaghan, DJ", journal = "Biophys J", keywords = "Action Potentials Anisotropy Body Surface Potential Mapping Computer Simulation Heart Conduction System Image Interpretation, Computer-Assisted Microscopy, Fluorescence Models, Cardiovascular Optics", number = "10", pages = "3957-8", title = "Inference of intramural wavefront orientation from optical recordings in realistic whole-heart models.", volume = "91", year = "2006", } @article{SynthesisVoltageSensitive, abstract = "Fluorescent photon scattering is known to distort optical recordings of cardiac transmembrane potentials; however, this process is not well quantified, hampering interpretation of experimental data. This study presents a novel model, which accurately synthesizes fluorescent recordings over the irregular geometry of the rabbit ventricles. Using the model, the study aims to provide quantification of fluorescent signal distortion for different optical characteristics of the preparation and of the surrounding medium. A bi-domain representation of electrical activity is combined with finite element solutions to the photon diffusion equation simulating both the excitation and emission processes, along with physically realistic boundary conditions at the epicardium, which allow simulation of different experimental setups. We demonstrate that distortion in the optical signal as a result of fluorescent photon scattering is truly a three-dimensional phenomenon and depends critically upon the geometry of the preparation, the scattering properties of the tissue, the direction of wavefront propagation, and the specifics of the experimental setup. Importantly, we show that in an anatomically accurate model of ventricular geometry and fiber orientation, the morphology of the optical signal does not provide reliable information regarding the intramural direction of wavefront propagation. These findings underscore the potential of the new model in interpreting experimental data.", author = "Bishop, MJ and Rodr{\'i}guez, B and Eason, J and Whiteley, JP and Trayanova, N and Gavaghan, DJ", journal = "Biophys J", keywords = "Animals Body Surface Potential Mapping Fluorescence Heart Membrane Potentials Models, Cardiovascular Pericardium Photons Rabbits Scattering, Radiation Signal Processing, Computer-Assisted", number = "8", pages = "2938-45", title = "Synthesis of voltage-sensitive optical signals: application to panoramic optical mapping.", volume = "90", year = "2006", } @article{EffectsPinacidil, abstract = "Many experimental studies have pointed out the controversy involving the arrhythmogenic effects of potassium channel openers (KCOs) in ischemia. KCOs activate the ATP-sensitive potassium current [IK(ATP)], resulting in action potential duration (APD) shortening, especially under pathological conditions such as ischemia. Acute myocardial ischemia leads to electrophysiological inhomogeneities in APD, conduction velocity, and refractoriness, which provide the substrate for reentry initiation and maintenance and may lead to malignant arrhythmias. The aim of this work is to analyze the effect of the KCO pinacidil on vulnerability to reentry during acute regional ischemia using computer simulations. We use a two-dimensional virtual heart tissue with implementation of acute regional ischemia conditions. Membrane kinetics are represented by a modified version of Luo-Rudy (phase II) action potential model that incorporates the effect of pinacidil on IK(ATP). The vulnerable window (VW) for reentry is quantified for different doses of pinacidil. Our results show that for doses below 3 micromol/l the VW widens with increasing pinacidil concentration, whereas for higher doses of pinacidil the VW decreases, becoming zero for concentrations above 10 micromol/l. The ionic mechanisms involved in this behavior are explored. This study demonstrates that the effect of pinacidil on arrhythmogenesis is strongly dose-dependent, and that high doses of pinacidil exert a strong antiarrhythmic effect.", author = "Tr{\'e}nor, B and Ferrero, JM Jr and Rodr{\'i}guez, B and Montilla, F", journal = "Ann Biomed Eng", keywords = "Action Potentials Animals Anti-Arrhythmia Agents Arrhythmias, Cardiac Computer Simulation Heart Conduction System Humans Models, Cardiovascular Myocardial Ischemia Pinacidil", number = "7", pages = "897-906", title = "Effects of pinacidil on reentrant arrhythmias generated during acute regional ischemia: a simulation study.", volume = "33", year = "2005", } @article{ChamberGeometry, abstract = "Although effects of shock strength and waveform on cardiac vulnerability to electric shocks have been extensively documented, the contribution of ventricular anatomy to shock-induced polarization and postshock propagation and thus, to shock outcome, has never been quantified; this is caused by lack of experimental methodology capable of mapping 3-D electrical activity. The goal of this study was to use optical imaging experiments and 3-D bidomain simulations to investigate the role of structural differences between left and right ventricles in vulnerability to electric shocks in rabbit hearts. The ventricles were paced apically, and uniform-field, truncated-exponential, monophasic shocks of reversed polarity were applied over a range of coupling intervals (CIs) in experiment and model. Experiments and simulations revealed that reversing the direction of externally-applied field (RV- or LV- shocks) alters the shape of the vulnerability area (VA), the 2-D grid encompassing episodes of arrhythmia induction. For RV- shocks, VA was nearly rectangular indicating little dependence of postshock arrhythmogenesis on CI. For LV- shocks, the probability of arrhythmia induction was higher for longer than for shorter CIs. The 3-D simulations demonstrated that these effects stem from the fact that reversal of field direction results in relocation of the main postshock excitable area from LV wall (RV- shocks) to septum (LV- shocks). Furthermore, the effect of septal (but not LV) excitable area in postshock propagation was found to strongly depend on preshock state. Knowledge regarding the location of the main postshock excitable area within the 3-D ventricular volume could be important for improving defibrillation efficacy.", author = "Rodr{\'i}guez, B and Li, L and Eason, JC and Efimov, IR and Trayanova, NA", journal = "Circ Res", keywords = "Animals Arrhythmia Body Surface Potential Mapping Computer Simulation Electric Countershock Heart Ventricles Membrane Potentials Rabbits", number = "2", pages = "168-75", title = "Differences between left and right ventricular chamber geometry affect cardiac vulnerability to electric shocks.", volume = "97", year = "2005", } @article{CardiacVulnerability, abstract = "OBJECTIVES: The purpose of this study is to characterize the changes in vulnerability to electric shocks during phase 1A of global ischemia in the rabbit ventricles and to determine the mechanisms responsible for these changes. BACKGROUND: Mechanisms responsible for the changes in cardiac vulnerability over the course of ischemia phase 1A remain poorly understood. The lack of understanding results from the rapid ischemic change in cardiac electrophysiologic properties, which renders experimental evaluation of vulnerability difficult. METHODS: To examine dynamic changes in vulnerability to electric shocks over the course of acute global ischemia phase 1A, this study used a three-dimensional anatomically accurate bidomain model of ischemic rabbit ventricles. Monophasic shocks are applied at various coupling intervals to construct vulnerability grids in normoxia and at various stages of ischemia phase 1A. RESULTS: Our simulations demonstrate that 2 to 3 minutes after the onset of ischemia, the upper limit of vulnerability remains at its normoxic value (12.75 V/cm); however, arrhythmias are induced at shorter coupling intervals. As ischemia progresses, the upper limit of vulnerability decreases, reaching 6.4 V/cm in the advanced stage of ischemia phase 1A, and the vulnerable window shifts towards longer coupling intervals. CONCLUSIONS: Changes in the upper limit of vulnerability result from an increase in the spatial extent of the shock-end excitation wavefronts and the slower recovery from shock-induced positive polarization. Shifts in the vulnerable window stem from decreases in local repolarization times and the occurrence of postshock conduction failure caused by prolonged postrepolarization refractoriness.", author = "Rodr{\'i}guez, B and Tice, BM and Eason, JC and Aguel, F and Trayanova, N", journal = "Heart Rhythm", keywords = "Action Potentials Animals Arrhythmia Computer Simulation Electric Countershock Heart Conduction System Heart Ventricles Models, Cardiovascular Myocardial Ischemia Rabbits", number = "6", pages = "695-703", title = "Cardiac vulnerability to electric shocks during phase 1A of acute global ischemia.", volume = "1", year = "2004", } @article{EffectOfAcute, abstract = "The goal of this modeling research is to provide mechanistic insight into the effect of altered membrane kinetics associated with 5-12 min of acute global ischemia on the upper limit of cardiac vulnerability (ULV) to electric shocks. We simulate electrical activity in a finite-element bidomain model of a 4-mm-thick slice through the canine ventricles that incorporates realistic geometry and fiber architecture. Global acute ischemia is represented by changes in membrane dynamics due to hyperkalemia, acidosis, and hypoxia. Two stages of acute ischemia are simulated corresponding to 5-7 min (stage 1) and 10-12 min (stage 2) after the onset of ischemia. Monophasic shocks are delivered in normoxia and ischemia over a range of coupling intervals, and their outcomes are examined to determine the highest shock strength that resulted in induction of reentrant arrhythmia. Our results demonstrate that acute ischemia stage 1 results in ULV reduction to 0.8A from its normoxic value of 1.4A. In contrast, no arrhythmia is induced regardless of shock strength in acute ischemia stage 2. An investigation of mechanisms underlying this behavior revealed that decreased postshock refractoriness resulting mainly from 1) ischemic electrophysiological substrate and 2) decrease in the extent of areas positively-polarized by the shock is responsible for the change in ULV during stage 1. In contrast, conduction failure is the main cause for the lack of vulnerability in acute ischemia stage 2. The insight provided by this study furthers our understanding of mechanisms by which acute ischemia-induced changes at the ionic level modulate cardiac vulnerability to electric shocks.", author = "Rodr{\'i}guez, B and Tice, BM and Eason, JC and Aguel, F and Ferrero, JM Jr and Trayanova, N", journal = "Am J Physiol Heart Circ Physiol", keywords = "Action Potentials Acute Disease Animals Arrhythmia Computer Simulation Dogs Electric Countershock Heart Conduction System Models, Cardiovascular Myocardial Ischemia Oxygen", number = "6", pages = "H2078-88", title = "Effect of acute global ischemia on the upper limit of vulnerability: a simulation study.", volume = "286", year = "2004", } @article{UpperLimit, abstract = "The goal of this modeling study is to investigate the mechanisms responsible for the upper and lower limits of vulnerability (ULV and LLV) to re-entry induced by electric shocks within the three-dimensional volume of the heart. We use a geometrically accurate rabbit ventricular model with realistic fiber architecture that also includes the blood in the cavities and a perfusing bath. The shocks are delivered over a range of strengths and coupling intervals via two large mesh electrodes located at the vertical boundaries of the perfusing bath. Our results demonstrate that shock-induced virtual electrode polarization (VEP) in the midmyocardium is weaker and more complex than VEP on the surfaces, where only 2 areas, one of positive and one of negative polarization, are induced. Transmural views of the ventricles show that, in all cases, tissue in the LV free wall and in the septum is deexcited by the shock providing an excitable path for wavefront propagation. Conversely, the RV free wall myocardium is depolarized after the end of the shock. The evolution of postshock electrical activity in the RV free wall plays a critical role in determining the outcome of the shock. In all cases, a wavefront starts in the apex at the site of largest transmembrane voltage gradient between oppositely polarized areas. For shocks of strength above the LLV, the postshock refractoriness of the RV free wall produces the unidirectional block necessary for reentry induction. If shock strength is below the ULV, the RV free wall recovers in time to provide the reentrant pathway. In contrast, for shocks of strength above the ULV, the postshock excitable gap in the LV free wall and in the septum is depolarized before the RV free wall recovers. Therefore, both ventricles are refractory and reentry is not induced", author = "Rodr{\'i}guez, B and Trayanova, N", journal = "J Electrocardiol", keywords = "Animals Electric Countershock Heart Septum Heart Ventricles Rabbits", pages = "51-6", title = "Upper limit of vulnerability in a defibrillation model of the rabbit ventricles.", volume = "36 Suppl", year = "2003", } @article{MechanisticInvestigation, abstract = "In this study, we have used computer simulations to study the mechanisms of extracellular K+ accumulation during acute ischemia. A modified version of the Luo-Rudy phase II action potential model was used to simulate the electrical behavior of one ventricular myocyte during 14 min of simulated ischemia. Our results show the following: 1) only the integrated effect of activation of ATP-dependent K+ current, an ischemic Na+ inward current, and inhibition of Na(+)-K(+) pump activity in the absence of coronary flow replicates the biphasic time course of extracellular K+ concentration observed during acute ischemia; 2) the time to onset of the plateau phase and the plateau level value are determined by the rate of stimulation and by the rate of alteration of the three mechanisms. However, acidosis and reduction of extracellular volume produce only a slight anticipation of the plateau phase; and 3) cellular K+ loss is mainly due to an increase of K+ efflux via the time-independent K+ current and ATP-dependent K+ current rather than to a decrease of K+ influx.", author = "Rodriguez, B and Ferrero, JM Jr and Trenor, B", journal = "Am J Physiol Heart Circ Physiol", keywords = "Acidosis Acute Disease Adenosine Triphosphate Computer Simulation Electric Conductivity Extracellular Space Heart Rate Humans Models, Cardiovascular Myocardial Ischemia Potassium Potassium Channels", number = "2", pages = "H490-500", title = "Mechanistic investigation of extracellular K+ accumulation during acute myocardial ischemia: a simulation study.", volume = "283", year = "2002", }