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Sample records for modeling cardiac electrophysiology

  1. Electrophysiological Cardiac Modeling: A Review.

    Science.gov (United States)

    Beheshti, Mohammadali; Umapathy, Karthikeyan; Krishnan, Sridhar

    2016-01-01

    Cardiac electrophysiological modeling in conjunction with experimental and clinical findings has contributed to better understanding of electrophysiological phenomena in various species. As our knowledge on underlying electrical, mechanical, and chemical processes has improved over time, mathematical models of the cardiac electrophysiology have become more realistic and detailed. These models have provided a testbed for various hypotheses and conditions that may not be easy to implement experimentally. In addition to the limitations in experimentally validating various scenarios implemented by the models, one of the major obstacles for these models is computational complexity. However, the ever-increasing computational power of supercomputers facilitates the clinical application of cardiac electrophysiological models. The potential clinical applications include testing and predicting effects of pharmaceutical agents and performing patient-specific ablation and defibrillation. A review of studies involving these models and their major findings are provided.

  2. Cardiac electrophysiological experiments in numero, Part II: Models of electrophysiological processes.

    Science.gov (United States)

    Malik, M; Camm, A J

    1991-11-01

    This article is the second part of a three article series reviewing computer simulation models of the heart, in particular of cardiac electrophysiology. The previous section of the review discussed the methodological principles of the construction and application of computer models. This article overviews the development of mathematical and computer modeling studies applied to cardiology. The models are classified according to the physiological processes that were simulated; this article distinguishes models oriented to cardiac mechanics, hemodynamics, and electrophysiology. The electrophysiology models are discussed in more detail and the review classifies them into four main categories: models of cellular processes, models of tissue behavior, models of the ventricular electric field, and models of macroconduction disturbances. In each category, the historical development of the models and their key achievements are described.

  3. Incorporating inductances in tissue-scale models of cardiac electrophysiology

    Science.gov (United States)

    Rossi, Simone; Griffith, Boyce E.

    2017-09-01

    In standard models of cardiac electrophysiology, including the bidomain and monodomain models, local perturbations can propagate at infinite speed. We address this unrealistic property by developing a hyperbolic bidomain model that is based on a generalization of Ohm's law with a Cattaneo-type model for the fluxes. Further, we obtain a hyperbolic monodomain model in the case that the intracellular and extracellular conductivity tensors have the same anisotropy ratio. In one spatial dimension, the hyperbolic monodomain model is equivalent to a cable model that includes axial inductances, and the relaxation times of the Cattaneo fluxes are strictly related to these inductances. A purely linear analysis shows that the inductances are negligible, but models of cardiac electrophysiology are highly nonlinear, and linear predictions may not capture the fully nonlinear dynamics. In fact, contrary to the linear analysis, we show that for simple nonlinear ionic models, an increase in conduction velocity is obtained for small and moderate values of the relaxation time. A similar behavior is also demonstrated with biophysically detailed ionic models. Using the Fenton-Karma model along with a low-order finite element spatial discretization, we numerically analyze differences between the standard monodomain model and the hyperbolic monodomain model. In a simple benchmark test, we show that the propagation of the action potential is strongly influenced by the alignment of the fibers with respect to the mesh in both the parabolic and hyperbolic models when using relatively coarse spatial discretizations. Accurate predictions of the conduction velocity require computational mesh spacings on the order of a single cardiac cell. We also compare the two formulations in the case of spiral break up and atrial fibrillation in an anatomically detailed model of the left atrium, and we examine the effect of intracellular and extracellular inductances on the virtual electrode phenomenon.

  4. Cellular cardiac electrophysiology modeling with Chaste and CellML.

    Science.gov (United States)

    Cooper, Jonathan; Spiteri, Raymond J; Mirams, Gary R

    2014-01-01

    Chaste is an open-source C++ library for computational biology that has well-developed cardiac electrophysiology tissue simulation support. In this paper, we introduce the features available for performing cardiac electrophysiology action potential simulations using a wide range of models from the Physiome repository. The mathematics of the models are described in CellML, with units for all quantities. The primary idea is that the model is defined in one place (the CellML file), and all model code is auto-generated at compile or run time; it never has to be manually edited. We use ontological annotation to identify model variables describing certain biological quantities (membrane voltage, capacitance, etc.) to allow us to import any relevant CellML models into the Chaste framework in consistent units and to interact with them via consistent interfaces. This approach provides a great deal of flexibility for analysing different models of the same system. Chaste provides a wide choice of numerical methods for solving the ordinary differential equations that describe the models. Fixed-timestep explicit and implicit solvers are provided, as discussed in previous work. Here we introduce the Rush-Larsen and Generalized Rush-Larsen integration techniques, made available via symbolic manipulation of the model equations, which are automatically rearranged into the forms required by these approaches. We have also integrated the CVODE solvers, a 'gold standard' for stiff systems, and we have developed support for symbolic computation of the Jacobian matrix, yielding further increases in the performance and accuracy of CVODE. We discuss some of the technical details of this work and compare the performance of the available numerical methods. Finally, we discuss how this is generalized in our functional curation framework, which uses a domain-specific language for defining complex experiments as a basis for comparison of model behavior.

  5. HCN channelopathy and cardiac electrophysiologic dysfunction in genetic and acquired rat epilepsy models.

    Science.gov (United States)

    Powell, Kim L; Jones, Nigel C; Kennard, Jeremy T; Ng, Caroline; Urmaliya, Vijay; Lau, Shannen; Tran, Adora; Zheng, Thomas; Ozturk, Ezgi; Dezsi, Gabi; Megatia, Ika; Delbridge, Lea M; Pinault, Didier; Reid, Christopher A; White, Paul J; O'Brien, Terence J

    2014-04-01

    Evidence from animal and human studies indicates that epilepsy can affect cardiac function, although the molecular basis of this remains poorly understood. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels generate pacemaker activity and modulate cellular excitability in the brain and heart, with altered expression and function associated with epilepsy and cardiomyopathies. Whether HCN expression is altered in the heart in association with epilepsy has not been investigated previously. We studied cardiac electrophysiologic properties and HCN channel subunit expression in rat models of genetic generalized epilepsy (Genetic Absence Epilepsy Rats from Strasbourg, GAERS) and acquired temporal lobe epilepsy (post-status epilepticus SE). We hypothesized that the development of epilepsy is associated with altered cardiac electrophysiologic function and altered cardiac HCN channel expression. Electrocardiography studies were recorded in vivo in rats and in vitro in isolated hearts. Cardiac HCN channel messenger RNA (mRNA) and protein expression were measured using quantitative PCR and Western blotting respectively. Cardiac electrophysiology was significantly altered in adult GAERS, with slower heart rate, shorter QRS duration, longer QTc interval, and greater standard deviation of RR intervals compared to control rats. In the post-SE model, we observed similar interictal changes in several of these parameters, and we also observed consistent and striking bradycardia associated with the onset of ictal activity. Molecular analysis demonstrated significant reductions in cardiac HCN2 mRNA and protein expression in both models, providing a molecular correlate of these electrophysiologic abnormalities. These results demonstrate that ion channelopathies and cardiac dysfunction can develop as a secondary consequence of chronic epilepsy, which may have relevance for the pathophysiology of cardiac dysfunction in patients with epilepsy. Wiley Periodicals, Inc.

  6. Automatic Segmentation of Cardiac CTs: Personalized Atrial Models Augmented with Electrophysiological Structures

    NARCIS (Netherlands)

    Neher, P.; Barschdorf, H.; Dries, S.; Weber, F.M.; Krueger, M.W.; Doessel, O.; Lorenz, C.

    2011-01-01

    Electrophysiological simulations of the atria could improve diagnosis and treatment of cardiac arrhythmia, like atrial fibrillation or flutter. For this purpose, a precise segmentation of both atria is needed. However, the atrial epicardium and the electrophysiological structures needed for electrop

  7. Modelling the effect of gap junctions on tissue-level cardiac electrophysiology

    CERN Document Server

    Bruce, Doug; Whiteley, Jonathan P

    2012-01-01

    When modelling tissue-level cardiac electrophysiology, continuum approximations to the discrete cell-level equations are used to maintain computational tractability. One of the most commonly used models is represented by the bidomain equations, the derivation of which relies on a homogenisation technique to construct a suitable approximation to the discrete model. This derivation does not explicitly account for the presence of gap junctions connecting one cell to another. It has been seen experimentally [Rohr, Cardiovasc. Res. 2004] that these gap junctions have a marked effect on the propagation of the action potential, specifically as the upstroke of the wave passes through the gap junction. In this paper we explicitly include gap junctions in a both a 2D discrete model of cardiac electrophysiology, and the corresponding continuum model, on a simplified cell geometry. Using these models we compare the results of simulations using both continuum and discrete systems. We see that the form of the action potent...

  8. Mathematical cardiac electrophysiology

    CERN Document Server

    Colli Franzone, Piero; Scacchi, Simone

    2014-01-01

    This book covers the main mathematical and numerical models in computational electrocardiology, ranging from microscopic membrane models of cardiac ionic channels to macroscopic bidomain, monodomain, eikonal models and cardiac source representations. These advanced multiscale and nonlinear models describe the cardiac bioelectrical activity from the cell level to the body surface and are employed in both the direct and inverse problems of electrocardiology. The book also covers advanced numerical techniques needed to efficiently carry out large-scale cardiac simulations, including time and space discretizations, decoupling and operator splitting techniques, parallel finite element solvers. These techniques are employed in 3D cardiac simulations illustrating the excitation mechanisms, the anisotropic effects on excitation and repolarization wavefronts, the morphology of electrograms in normal and pathological tissue and some reentry phenomena. The overall aim of the book is to present rigorously the mathematica...

  9. Reduced-order modeling for cardiac electrophysiology. Application to parameter identification

    CERN Document Server

    Boulakia, Muriel; Gerbeau, Jean-Frédéric

    2011-01-01

    A reduced-order model based on Proper Orthogonal Decomposition (POD) is proposed for the bidomain equations of cardiac electrophysiology. Its accuracy is assessed through electrocardiograms in various configurations, including myocardium infarctions and long-time simulations. We show in particular that a restitution curve can efficiently be approximated by this approach. The reduced-order model is then used in an inverse problem solved by an evolutionary algorithm. Some attempts are presented to identify ionic parameters and infarction locations from synthetic ECGs.

  10. Parallel Optimization of 3D Cardiac Electrophysiological Model Using GPU

    Directory of Open Access Journals (Sweden)

    Yong Xia

    2015-01-01

    Full Text Available Large-scale 3D virtual heart model simulations are highly demanding in computational resources. This imposes a big challenge to the traditional computation resources based on CPU environment, which already cannot meet the requirement of the whole computation demands or are not easily available due to expensive costs. GPU as a parallel computing environment therefore provides an alternative to solve the large-scale computational problems of whole heart modeling. In this study, using a 3D sheep atrial model as a test bed, we developed a GPU-based simulation algorithm to simulate the conduction of electrical excitation waves in the 3D atria. In the GPU algorithm, a multicellular tissue model was split into two components: one is the single cell model (ordinary differential equation and the other is the diffusion term of the monodomain model (partial differential equation. Such a decoupling enabled realization of the GPU parallel algorithm. Furthermore, several optimization strategies were proposed based on the features of the virtual heart model, which enabled a 200-fold speedup as compared to a CPU implementation. In conclusion, an optimized GPU algorithm has been developed that provides an economic and powerful platform for 3D whole heart simulations.

  11. Comparison of Nigella sativa- and exercise-induced models of cardiac hypertrophy: structural and electrophysiological features.

    Science.gov (United States)

    Al-Asoom, Lubna Ibrahim; Al-Shaikh, Basil Abdulrahman; Bamosa, Abdullah Omar; El-Bahai, Mohammad Nabil

    2014-09-01

    Exercise training is employed as supplementary therapeutic intervention for heart failure, due to its ability to induce physiological cardiac hypertrophy. In parallel, supplementation with Nigella sativa (N. sativa) was found to enhance myocardial function and induce cardiac hypertrophy. In this study, we aim to compare the morphological and electrophysiological changes associated with these patterns of cardiac hypertrophy and the possible changes upon administration of N. sativa to exercise-trained animals. Fifty-six adult Wistar rats were divided into: control, Nigella-treated (N), exercise-trained (E), and Nigella-treated-exercise-trained (NE) rats. Daily 800 mg/kg N. sativa was administered orally to N and NE. E and NE ran on treadmill, 2 h/day. At the end of 8 weeks ECG, body weight (BW), heart weight (HW), and left ventricular weight (LVW) were recorded. Hematoxylin and Eosin and periodic acid-Schiff sections were prepared to study the histology of left ventricles and to measure diameter of cardiomyocytes (Cdia). HW/BW, LVW/BW, and mean Cdia were significantly higher in all experimental animals compared to the controls. Histology showed normal cardiomyocytes with no fibrosis. ECG showed significantly lower heart rates, higher QRS amplitude, and ventricular specific potential in NE group compared to control group. Supplementation of N. sativa demonstrated a synergistic effect with exercise training as Nigella-exercise-induced cardiac hypertrophy had lower heart rate and well-matched electrical activity of the heart to its mass. Therefore, this model of cardiac hypertrophy might be introduced as a new therapeutic strategy for treatment for heart failure with superior advantages to exercise training.

  12. Coupled personalization of cardiac electrophysiology models for prediction of ischaemic ventricular tachycardia.

    Science.gov (United States)

    Relan, Jatin; Chinchapatnam, Phani; Sermesant, Maxime; Rhode, Kawal; Ginks, Matt; Delingette, Hervé; Rinaldi, C Aldo; Razavi, Reza; Ayache, Nicholas

    2011-06-06

    In order to translate the important progress in cardiac electrophysiology modelling of the last decades into clinical applications, there is a requirement to make macroscopic models that can be used for the planning and performance of the clinical procedures. This requires model personalization, i.e. estimation of patient-specific model parameters and computations compatible with clinical constraints. Simplified macroscopic models can allow a rapid estimation of the tissue conductivity, but are often unreliable to predict arrhythmias. Conversely, complex biophysical models are more complete and have mechanisms of arrhythmogenesis and arrhythmia sustainibility, but are computationally expensive and their predictions at the organ scale still have to be validated. We present a coupled personalization framework that combines the power of the two kinds of models while keeping the computational complexity tractable. A simple eikonal model is used to estimate the conductivity parameters, which are then used to set the parameters of a biophysical model, the Mitchell-Schaeffer (MS) model. Additional parameters related to action potential duration restitution curves for the tissue are further estimated for the MS model. This framework is applied to a clinical dataset derived from a hybrid X-ray/magnetic resonance imaging and non-contact mapping procedure on a patient with heart failure. This personalized MS model is then used to perform an in silico simulation of a ventricular tachycardia (VT) stimulation protocol to predict the induction of VT. This proof of concept opens up possibilities of using VT induction modelling in order to both assess the risk of VT for a given patient and also to plan a potential subsequent radio-frequency ablation strategy to treat VT.

  13. Quantitative analysis of cardiac tissue including fibroblasts using three-dimensional confocal microscopy and image reconstruction: towards a basis for electrophysiological modeling

    NARCIS (Netherlands)

    Schwab, Bettina C.; Seemann, Gunnar; Lasher, Richard A.; Torres, Natalia S.; Wülfers, Eike M.; Arp, Maren; Carruth, Eric D.; Bridge, John H.B.; Sachse, Frank B.

    2013-01-01

    Electrophysiological modeling of cardiac tissue is commonly based on functional and structural properties measured in experiments. Our knowledge of these properties is incomplete, in particular their remodeling in disease. Here, we introduce a methodology for quantitative tissue characterization bas

  14. Minimum Information about a Cardiac Electrophysiology Experiment (MICEE)

    DEFF Research Database (Denmark)

    Quinn, T A; Granite, S; Allessie, M A;

    2011-01-01

    Cardiac experimental electrophysiology is in need of a well-defined Minimum Information Standard for recording, annotating, and reporting experimental data. As a step towards establishing this, we present a draft standard, called Minimum Information about a Cardiac Electrophysiology Experiment....... It is hoped that this will enhance the integration of individual results into experimental, computational, and conceptual models. In its present form, this draft is intended for assessment and development by the research community. We invite the reader to join this effort, and, if deemed productive, implement...... the Minimum Information about a Cardiac Electrophysiology Experiment standard in their own work....

  15. Parametrization of activation based cardiac electrophysiology models using bidomain model simulations

    Directory of Open Access Journals (Sweden)

    Stender Birgit

    2016-09-01

    Full Text Available Eikonal models are useful to compute approximate solutions of cardiac excitation propagation in a computationally efficient way. In this work the underlying conduction velocities for different cell types were computed solving the classical bidomain model equations for planar wavefront propagation. It was further investigated how changes in the conductivity tensors within the bidomain model analytically correspond to changes in the conduction velocity. The error in the presence of local front curvature for the derived eikonal model parametrization were analyzed. The conduction velocity simulated based on the bidomain model was overestimated by a maximum of 10%.

  16. Efficient probabilistic model personalization integrating uncertainty on data and parameters: Application to eikonal-diffusion models in cardiac electrophysiology.

    Science.gov (United States)

    Konukoglu, Ender; Relan, Jatin; Cilingir, Ulas; Menze, Bjoern H; Chinchapatnam, Phani; Jadidi, Amir; Cochet, Hubert; Hocini, Mélèze; Delingette, Hervé; Jaïs, Pierre; Haïssaguerre, Michel; Ayache, Nicholas; Sermesant, Maxime

    2011-10-01

    Biophysical models are increasingly used for medical applications at the organ scale. However, model predictions are rarely associated with a confidence measure although there are important sources of uncertainty in computational physiology methods. For instance, the sparsity and noise of the clinical data used to adjust the model parameters (personalization), and the difficulty in modeling accurately soft tissue physiology. The recent theoretical progresses in stochastic models make their use computationally tractable, but there is still a challenge in estimating patient-specific parameters with such models. In this work we propose an efficient Bayesian inference method for model personalization using polynomial chaos and compressed sensing. This method makes Bayesian inference feasible in real 3D modeling problems. We demonstrate our method on cardiac electrophysiology. We first present validation results on synthetic data, then we apply the proposed method to clinical data. We demonstrate how this can help in quantifying the impact of the data characteristics on the personalization (and thus prediction) results. Described method can be beneficial for the clinical use of personalized models as it explicitly takes into account the uncertainties on the data and the model parameters while still enabling simulations that can be used to optimize treatment. Such uncertainty handling can be pivotal for the proper use of modeling as a clinical tool, because there is a crucial requirement to know the confidence one can have in personalized models.

  17. Depth Attenuation Degree Based Visualization for Cardiac Ischemic Electrophysiological Feature Exploration

    Science.gov (United States)

    Liu, Lei; Zuo, Wangmeng; Zhang, Henggui

    2016-01-01

    Although heart researches and acquirement of clinical and experimental data are progressively open to public use, cardiac biophysical functions are still not well understood. Due to the complex and fine structures of the heart, cardiac electrophysiological features of interest may be occluded when there is a necessity to demonstrate cardiac electrophysiological behaviors. To investigate cardiac abnormal electrophysiological features under the pathological condition, in this paper, we implement a human cardiac ischemic model and acquire the electrophysiological data of excitation propagation. A visualization framework is then proposed which integrates a novel depth weighted optic attenuation model into the pathological electrophysiological model. The hidden feature of interest in pathological tissue can be revealed from sophisticated overlapping biophysical information. Experiment results verify the effectiveness of the proposed method for intuitively exploring and inspecting cardiac electrophysiological activities, which is fundamental in analyzing and explaining biophysical mechanisms of cardiac functions for doctors and medical staff. PMID:28004002

  18. Image-based reconstruction of three-dimensional myocardial infarct geometry for patient-specific modeling of cardiac electrophysiology

    Energy Technology Data Exchange (ETDEWEB)

    Ukwatta, Eranga, E-mail: eukwatt1@jhu.edu; Arevalo, Hermenegild; Pashakhanloo, Farhad; Prakosa, Adityo; Vadakkumpadan, Fijoy [Institute for Computational Medicine, Johns Hopkins University, Baltimore, Maryland 21205 and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland 21205 (United States); Rajchl, Martin [Department of Computing, Imperial College London, London SW7 2AZ (United Kingdom); White, James [Stephenson Cardiovascular MR Centre, University of Calgary, Calgary, Alberta T2N 2T9 (Canada); Herzka, Daniel A.; McVeigh, Elliot [Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland 21205 (United States); Lardo, Albert C. [Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland 21205 and Division of Cardiology, Johns Hopkins Institute of Medicine, Baltimore, Maryland 21224 (United States); Trayanova, Natalia A. [Institute for Computational Medicine, Johns Hopkins University, Baltimore, Maryland 21205 (United States); Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland 21205 (United States); Department of Biomedical Engineering, Johns Hopkins Institute of Medicine, Baltimore, Maryland 21205 (United States)

    2015-08-15

    Purpose: Accurate three-dimensional (3D) reconstruction of myocardial infarct geometry is crucial to patient-specific modeling of the heart aimed at providing therapeutic guidance in ischemic cardiomyopathy. However, myocardial infarct imaging is clinically performed using two-dimensional (2D) late-gadolinium enhanced cardiac magnetic resonance (LGE-CMR) techniques, and a method to build accurate 3D infarct reconstructions from the 2D LGE-CMR images has been lacking. The purpose of this study was to address this need. Methods: The authors developed a novel methodology to reconstruct 3D infarct geometry from segmented low-resolution (Lo-res) clinical LGE-CMR images. Their methodology employed the so-called logarithm of odds (LogOdds) function to implicitly represent the shape of the infarct in segmented image slices as LogOdds maps. These 2D maps were then interpolated into a 3D image, and the result transformed via the inverse of LogOdds to a binary image representing the 3D infarct geometry. To assess the efficacy of this method, the authors utilized 39 high-resolution (Hi-res) LGE-CMR images, including 36 in vivo acquisitions of human subjects with prior myocardial infarction and 3 ex vivo scans of canine hearts following coronary ligation to induce infarction. The infarct was manually segmented by trained experts in each slice of the Hi-res images, and the segmented data were downsampled to typical clinical resolution. The proposed method was then used to reconstruct 3D infarct geometry from the downsampled images, and the resulting reconstructions were compared with the manually segmented data. The method was extensively evaluated using metrics based on geometry as well as results of electrophysiological simulations of cardiac sinus rhythm and ventricular tachycardia in individual hearts. Several alternative reconstruction techniques were also implemented and compared with the proposed method. Results: The accuracy of the LogOdds method in reconstructing 3D

  19. Uncertainty quantification of fast sodium current steady-state inactivation for multi-scale models of cardiac electrophysiology.

    Science.gov (United States)

    Pathmanathan, Pras; Shotwell, Matthew S; Gavaghan, David J; Cordeiro, Jonathan M; Gray, Richard A

    2015-01-01

    Perhaps the most mature area of multi-scale systems biology is the modelling of the heart. Current models are grounded in over fifty years of research in the development of biophysically detailed models of the electrophysiology (EP) of cardiac cells, but one aspect which is inadequately addressed is the incorporation of uncertainty and physiological variability. Uncertainty quantification (UQ) is the identification and characterisation of the uncertainty in model parameters derived from experimental data, and the computation of the resultant uncertainty in model outputs. It is a necessary tool for establishing the credibility of computational models, and will likely be expected of EP models for future safety-critical clinical applications. The focus of this paper is formal UQ of one major sub-component of cardiac EP models, the steady-state inactivation of the fast sodium current, INa. To better capture average behaviour and quantify variability across cells, we have applied for the first time an 'individual-based' statistical methodology to assess voltage clamp data. Advantages of this approach over a more traditional 'population-averaged' approach are highlighted. The method was used to characterise variability amongst cells isolated from canine epi and endocardium, and this variability was then 'propagated forward' through a canine model to determine the resultant uncertainty in model predictions at different scales, such as of upstroke velocity and spiral wave dynamics. Statistically significant differences between epi and endocardial cells (greater half-inactivation and less steep slope of steady state inactivation curve for endo) was observed, and the forward propagation revealed a lack of robustness of the model to underlying variability, but also surprising robustness to variability at the tissue scale. Overall, the methodology can be used to: (i) better analyse voltage clamp data; (ii) characterise underlying population variability; (iii) investigate

  20. Cardiac Electrophysiology: Normal and Ischemic Ionic Currents and the ECG

    Science.gov (United States)

    Klabunde, Richard E.

    2017-01-01

    Basic cardiac electrophysiology is foundational to understanding normal cardiac function in terms of rate and rhythm and initiation of cardiac muscle contraction. The primary clinical tool for assessing cardiac electrical events is the electrocardiogram (ECG), which provides global and regional information on rate, rhythm, and electrical…

  1. Cardiac electrophysiological experiments in numero, Part I: Concepts and strategies of mathematical and computer models.

    Science.gov (United States)

    Malik, M; Camm, A J

    1991-10-01

    This article is the first of three articles that review mathematical and computer models of the heart and describe their construction, development, research potential, and clinical utility. This article explains the methodological principles of mathematical and computer simulation of biomedical systems. The strategies of model construction, testing, and application are presented; the advantages and limitations of computer simulation studies are explained, and the basic value of computer simulation for cardiological research and practice is discussed.

  2. Myokit: A simple interface to cardiac cellular electrophysiology.

    Science.gov (United States)

    Clerx, Michael; Collins, Pieter; de Lange, Enno; Volders, Paul G A

    2016-01-01

    Myokit is a new powerful and versatile software tool for modeling and simulation of cardiac cellular electrophysiology. Myokit consists of an easy-to-read modeling language, a graphical user interface, single and multi-cell simulation engines and a library of advanced analysis tools accessible through a Python interface. Models can be loaded from Myokit's native file format or imported from CellML. Model export is provided to C, MATLAB, CellML, CUDA and OpenCL. Patch-clamp data can be imported and used to estimate model parameters. In this paper, we review existing tools to simulate the cardiac cellular action potential to find that current tools do not cater specifically to model development and that there is a gap between easy-to-use but limited software and powerful tools that require strong programming skills from their users. We then describe Myokit's capabilities, focusing on its model description language, simulation engines and import/export facilities in detail. Using three examples, we show how Myokit can be used for clinically relevant investigations, multi-model testing and parameter estimation in Markov models, all with minimal programming effort from the user. This way, Myokit bridges a gap between performance, versatility and user-friendliness. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Cardiac differentiation and electrophysiology characteristics of bone marrow mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    LIU Bo-wu; AI Shi-yi; L(U) An-lin; HOU Jing; HUANG Wei; LI Yao; HOU Zhao-lei; HOU Hong; DA Jing; YANG Na

    2012-01-01

    Objective To review the progress of cardiac differentiation and electrophysiological characteristics of bone marrow mesenchymal stem cells.Data sources The databases of PubMed,Springer Link,Science Direct and CNKI were retrieved for papers published from January 2000 to January 2012 with the key words of “bone marrow mesenchymal stem cells,cardiac or heart,electrophysiology or electrophysiological characteristics”.Study selection The articles concerned cardiac differentiation and electrophysiological characteristics of bone marrow mesenchymal stem cells were collected.After excluding papers that study purposes are not coincident with this review or contents duplicated,56 papers were internalized at last.Results For the treatment of myocardial infarction and myocardiac disease,the therapeutic effects of transplantation of bone marrow mesenchymal stem cells which have the ability to develop into functional myocardial cells by lots of methods have been proved by many researches.But the arrhythmogenic effect on ventricles affer transplantation of bone marrow mesenchymal stem cells derived myocardial cells is still controversial in animal models.Certainly,the low differentiation efficiency and heterogeneous development of electricial function could be the most important risk for proarrhythmia.Conclusion Many studies of cardiac differentiation of bone marrow mesenchymal stem cells have paid attention to improve the cardiac differentiation rate,and the electrophysiology characteristics of the differentiated cells should be concerned for the risk for proarrhythmia as well.

  4. Human cardiac systems electrophysiology and arrhythmogenesis: iteration of experiment and computation.

    Science.gov (United States)

    Holzem, Katherine M; Madden, Eli J; Efimov, Igor R

    2014-11-01

    Human cardiac electrophysiology (EP) is a unique system for computational modelling at multiple scales. Due to the complexity of the cardiac excitation sequence, coordinated activity must occur from the single channel to the entire myocardial syncytium. Thus, sophisticated computational algorithms have been developed to investigate cardiac EP at the level of ion channels, cardiomyocytes, multicellular tissues, and the whole heart. Although understanding of each functional level will ultimately be important to thoroughly understand mechanisms of physiology and disease, cardiac arrhythmias are expressly the product of cardiac tissue-containing enough cardiomyocytes to sustain a reentrant loop of activation. In addition, several properties of cardiac cellular EP, that are critical for arrhythmogenesis, are significantly altered by cell-to-cell coupling. However, relevant human cardiac EP data, upon which to develop or validate models at all scales, has been lacking. Thus, over several years, we have developed a paradigm for multiscale human heart physiology investigation and have recovered and studied over 300 human hearts. We have generated a rich experimental dataset, from which we better understand mechanisms of arrhythmia in human and can improve models of human cardiac EP. In addition, in collaboration with computational physiologists, we are developing a database for the deposition of human heart experimental data, including thorough experimental documentation. We anticipate that accessibility to this human heart dataset will further human EP computational investigations, as well as encourage greater data transparency within the field of cardiac EP.

  5. Cardiac electrophysiological experiments in numero, Part III: Simulation of arrhythmias and pacing.

    Science.gov (United States)

    Malik, M; Camm, A J

    1991-12-01

    This paper is the third and final part of a series of articles reviewing mathematical and computer models of the electrophysiological processes. This section reviews the arrhythmia simulation and discusses models of arrhythmogenic processes, fibrillation and defibrillation, and of heart-pacemaker interaction. The models of arrhythmogenesis are classified into three main sections: models of reentry and vortex reentry, models of myocardial electrotonic interactions, and models of macroreentrant supraventricular tachycardias. This final part of the review discusses the future potential of mathematical and computer models of different cardiac processes.

  6. Computational approaches to understand cardiac electrophysiology and arrhythmias

    Science.gov (United States)

    Roberts, Byron N.; Yang, Pei-Chi; Behrens, Steven B.; Moreno, Jonathan D.

    2012-01-01

    Cardiac rhythms arise from electrical activity generated by precisely timed opening and closing of ion channels in individual cardiac myocytes. These impulses spread throughout the cardiac muscle to manifest as electrical waves in the whole heart. Regularity of electrical waves is critically important since they signal the heart muscle to contract, driving the primary function of the heart to act as a pump and deliver blood to the brain and vital organs. When electrical activity goes awry during a cardiac arrhythmia, the pump does not function, the brain does not receive oxygenated blood, and death ensues. For more than 50 years, mathematically based models of cardiac electrical activity have been used to improve understanding of basic mechanisms of normal and abnormal cardiac electrical function. Computer-based modeling approaches to understand cardiac activity are uniquely helpful because they allow for distillation of complex emergent behaviors into the key contributing components underlying them. Here we review the latest advances and novel concepts in the field as they relate to understanding the complex interplay between electrical, mechanical, structural, and genetic mechanisms during arrhythmia development at the level of ion channels, cells, and tissues. We also discuss the latest computational approaches to guiding arrhythmia therapy. PMID:22886409

  7. Zebrafish: a novel research tool for cardiac (patho)electrophysiology and ion channel disorders.

    Science.gov (United States)

    Verkerk, Arie O; Remme, Carol Ann

    2012-01-01

    The zebrafish is a cold-blooded tropical freshwater teleost with two-chamber heart morphology. A major advantage of the zebrafish for heart studies is that the embryo is transparent, allowing for easy assessment of heart development, heart rate analysis and phenotypic characterization. Moreover, rapid and effective gene-specific knockdown can be achieved using morpholino oligonucleotides. Lastly, zebrafish are small in size, are easy to maintain and house, grow fast, and have large offspring size, making them a cost-efficient research model. Zebrafish embryonic and adult heart rates as well as action potential (AP) shape and duration and electrocardiogram morphology closely resemble those of humans. However, whether the zebrafish is truly an attractive alternative model for human cardiac electrophysiology depends on the presence and gating properties of the various ion channels in the zebrafish heart, but studies into the latter are as yet limited. The rapid component of the delayed rectifier K(+) current (I(Kr)) remains the best characterized and validated ion current in zebrafish myocytes, and zebrafish may represent a valuable model to investigate human I(Kr) channel-related disease, including long QT syndrome. Arguments against the use of zebrafish as model for human cardiac (patho)electrophysiology include its cold-bloodedness and two-chamber heart morphology, absence of t-tubuli, sarcoplamatic reticulum function, and a different profile of various depolarizing and repolarizing ion channels, including a limited Na(+) current density. Based on the currently available literature, we propose that zebrafish may constitute a relevant research model for investigating ion channel disorders associated with abnormal repolarization, but may be less suitable for studying depolarization disorders or Ca(2+)-modulated arrhythmias.

  8. Hormones and sex differences: changes in cardiac electrophysiology with pregnancy.

    Science.gov (United States)

    Bett, Glenna C L

    2016-05-01

    Disruption of cardiac electrical activity resulting in palpitations and syncope is often an early symptom of pregnancy. Pregnancy is a time of dramatic and dynamic physiological and hormonal changes during which numerous demands are placed on the heart. These changes result in electrical remodelling which can be detected as changes in the electrocardiogram (ECG). This gestational remodelling is a very under-researched area. There are no systematic large studies powered to determine changes in the ECG from pre-pregnancy, through gestation, and into the postpartum period. The large variability between patients and the dynamic nature of pregnancy hampers interpretation of smaller studies, but some facts are consistent. Gestational cardiac hypertrophy and a physical shift of the heart contribute to changes in the ECG. There are also electrical changes such as an increased heart rate and lengthening of the QT interval. There is an increased susceptibility to arrhythmias during pregnancy and the postpartum period. Some changes in the ECG are clearly the result of changes in ion channel expression and behaviour, but little is known about the ionic basis for this electrical remodelling. Most information comes from animal models, and implicates changes in the delayed-rectifier channels. However, it is likely that there are additional roles for sodium channels as well as changes in calcium homoeostasis. The changes in the electrical profile of the heart during pregnancy and the postpartum period have clear implications for the safety of pregnant women, but the field remains relatively undeveloped.

  9. Program Code Generator for Cardiac Electrophysiology Simulation with Automatic PDE Boundary Condition Handling.

    Science.gov (United States)

    Punzalan, Florencio Rusty; Kunieda, Yoshitoshi; Amano, Akira

    2015-01-01

    Clinical and experimental studies involving human hearts can have certain limitations. Methods such as computer simulations can be an important alternative or supplemental tool. Physiological simulation at the tissue or organ level typically involves the handling of partial differential equations (PDEs). Boundary conditions and distributed parameters, such as those used in pharmacokinetics simulation, add to the complexity of the PDE solution. These factors can tailor PDE solutions and their corresponding program code to specific problems. Boundary condition and parameter changes in the customized code are usually prone to errors and time-consuming. We propose a general approach for handling PDEs and boundary conditions in computational models using a replacement scheme for discretization. This study is an extension of a program generator that we introduced in a previous publication. The program generator can generate code for multi-cell simulations of cardiac electrophysiology. Improvements to the system allow it to handle simultaneous equations in the biological function model as well as implicit PDE numerical schemes. The replacement scheme involves substituting all partial differential terms with numerical solution equations. Once the model and boundary equations are discretized with the numerical solution scheme, instances of the equations are generated to undergo dependency analysis. The result of the dependency analysis is then used to generate the program code. The resulting program code are in Java or C programming language. To validate the automatic handling of boundary conditions in the program code generator, we generated simulation code using the FHN, Luo-Rudy 1, and Hund-Rudy cell models and run cell-to-cell coupling and action potential propagation simulations. One of the simulations is based on a published experiment and simulation results are compared with the experimental data. We conclude that the proposed program code generator can be used to

  10. Program Code Generator for Cardiac Electrophysiology Simulation with Automatic PDE Boundary Condition Handling.

    Directory of Open Access Journals (Sweden)

    Florencio Rusty Punzalan

    Full Text Available Clinical and experimental studies involving human hearts can have certain limitations. Methods such as computer simulations can be an important alternative or supplemental tool. Physiological simulation at the tissue or organ level typically involves the handling of partial differential equations (PDEs. Boundary conditions and distributed parameters, such as those used in pharmacokinetics simulation, add to the complexity of the PDE solution. These factors can tailor PDE solutions and their corresponding program code to specific problems. Boundary condition and parameter changes in the customized code are usually prone to errors and time-consuming. We propose a general approach for handling PDEs and boundary conditions in computational models using a replacement scheme for discretization. This study is an extension of a program generator that we introduced in a previous publication. The program generator can generate code for multi-cell simulations of cardiac electrophysiology. Improvements to the system allow it to handle simultaneous equations in the biological function model as well as implicit PDE numerical schemes. The replacement scheme involves substituting all partial differential terms with numerical solution equations. Once the model and boundary equations are discretized with the numerical solution scheme, instances of the equations are generated to undergo dependency analysis. The result of the dependency analysis is then used to generate the program code. The resulting program code are in Java or C programming language. To validate the automatic handling of boundary conditions in the program code generator, we generated simulation code using the FHN, Luo-Rudy 1, and Hund-Rudy cell models and run cell-to-cell coupling and action potential propagation simulations. One of the simulations is based on a published experiment and simulation results are compared with the experimental data. We conclude that the proposed program code

  11. Teaching Cardiac Electrophysiology Modeling to Undergraduate Students: Laboratory Exercises and GPU Programming for the Study of Arrhythmias and Spiral Wave Dynamics

    Science.gov (United States)

    Bartocci, Ezio; Singh, Rupinder; von Stein, Frederick B.; Amedome, Avessie; Caceres, Alan Joseph J.; Castillo, Juan; Closser, Evan; Deards, Gabriel; Goltsev, Andriy; Ines, Roumwelle Sta.; Isbilir, Cem; Marc, Joan K.; Moore, Diquan; Pardi, Dana; Sadhu, Sandeep; Sanchez, Samuel; Sharma, Pooja; Singh, Anoopa; Rogers, Joshua; Wolinetz, Aron; Grosso-Applewhite, Terri; Zhao, Kai; Filipski, Andrew B.; Gilmour, Robert F., Jr.; Grosu, Radu; Glimm, James; Smolka, Scott A.; Cherry, Elizabeth M.; Clarke, Edmund M.; Griffeth, Nancy; Fenton, Flavio H.

    2011-01-01

    As part of a 3-wk intersession workshop funded by a National Science Foundation Expeditions in Computing award, 15 undergraduate students from the City University of New York collaborated on a study aimed at characterizing the voltage dynamics and arrhythmogenic behavior of cardiac cells for a broad range of physiologically relevant conditions…

  12. BeatBox—HPC simulation environment for biophysically and anatomically realistic cardiac electrophysiology

    Science.gov (United States)

    Antonioletti, Mario; Biktashev, Vadim N.; Jackson, Adrian; Kharche, Sanjay R.; Stary, Tomas

    2017-01-01

    The BeatBox simulation environment combines flexible script language user interface with the robust computational tools, in order to setup cardiac electrophysiology in-silico experiments without re-coding at low-level, so that cell excitation, tissue/anatomy models, stimulation protocols may be included into a BeatBox script, and simulation run either sequentially or in parallel (MPI) without re-compilation. BeatBox is a free software written in C language to be run on a Unix-based platform. It provides the whole spectrum of multi scale tissue modelling from 0-dimensional individual cell simulation, 1-dimensional fibre, 2-dimensional sheet and 3-dimensional slab of tissue, up to anatomically realistic whole heart simulations, with run time measurements including cardiac re-entry tip/filament tracing, ECG, local/global samples of any variables, etc. BeatBox solvers, cell, and tissue/anatomy models repositories are extended via robust and flexible interfaces, thus providing an open framework for new developments in the field. In this paper we give an overview of the BeatBox current state, together with a description of the main computational methods and MPI parallelisation approaches. PMID:28467407

  13. Cardiac and electrophysiological effects of primary and refined extracts from Leonurus cardiaca L. (Ph.Eur.).

    Science.gov (United States)

    Ritter, Malte; Melichar, Kerstin; Strahler, Sabine; Kuchta, Kenny; Schulte, Jan; Sartiani, Laura; Cerbai, Elisabetta; Mugelli, Alessandro; Mohr, Friedrich-Wilhelm; Rauwald, Hans Wilhelm; Dhein, Stefan

    2010-04-01

    Although several antiarrhythmic drugs of chemical origin are in clinical use since decades, their application is often limited by their adverse effects and especially by their inherited proarrhythmic risk, which can lead to a significantly increased mortality in patients receiving these compounds. On the other hand, aqueous extracts from the aerial parts of the European Lamiaceae Leonurus cardiaca (Ph.Eur.) have been used for centuries as a remedy against tachyarrhythmia and other cardiac disorders. Nevertheless, a scientific basis for the claim of direct cardiac electrophysiological, antiarrhythmic, or functional effects of Leonurus cardiacae herba (LCH) preparations has not been established until now. In order to enrich the active constituents from the primary extract which was tested as the most cardioactive, namely the aqueous Soxhlet extract, and to eliminate undesired substances such as the dichloromethanic fraction or potassium, a bioassay guided fractionation procedure was applied, resulting in the development of a Leonurus cardiaca refined extract (LCRE) which was characterised together with Leonurus crude extracts by a newly developed gradient elution HPLC fingerprint analysis for separation and quantification of six major phenolics as well as by qNMR for determining the stachydrine content. This refined extract was applied intracoronarily in isolated rabbit hearts perfused according to the Langendorff technique. Mapping experiments with 256 electrodes on the heart surface showed a reduction of left ventricular pressure and an increase of relative coronary flow at concentrations of 1.0 and 2.0 mg/mL LCRE. Furthermore, the PQ-interval was prolonged and both the basic cycle length and the activation recovery interval increased. In addition, voltage-clamp measurements were performed on the following cell models in order to characterise the electrophysiological profile of LCRE: neonatal rat ventricular cardiomyocytes to investigate the effect on I(Na) and I

  14. Electrophysiologic testing guided risk stratification approach for sudden cardiac death beyond the left ventricular ejection fraction.

    Science.gov (United States)

    Gatzoulis, Konstantinos A; Tsiachris, Dimitris; Arsenos, Petros; Tousoulis, Dimitris

    2016-01-26

    Sudden cardiac death threats ischaemic and dilated cardiomyopathy patients. Anti- arrhythmic protection may be provided to these patients with implanted cardiac defibrillators (ICD), after an efficient risk stratification approach. The proposed risk stratifier of an impaired left ventricular ejection fraction has limited sensitivity meaning that a significant number of victims will remain undetectable by this risk stratification approach because they have a preserved left ventricular systolic function. Current risk stratification strategies focus on combinations of non invasive methods like T wave alternans, late potentials, heart rate turbulence, deceleration capacity and others, with invasive methods like the electrophysiologic study. In the presence of an electrically impaired substrate with formed post myocardial infarction fibrotic zones, programmed ventricular stimulation provides important prognostic information for the selection of the patients expected to benefit from an ICD implantation, while due to its high negative predictive value, patients at low risk level may also be detected. Clustering evidence from different research groups and electrophysiologic labs support an electrophysiologic testing guided risk stratification approach for sudden cardiac death.

  15. Electrophysiologic testing guided risk stratification approach for sudden cardiac death beyond the left ventricular ejection fraction

    Institute of Scientific and Technical Information of China (English)

    Konstantinos A Gatzoulis; Dimitris Tsiachris; Petros Arsenos; Dimitris Tousoulis

    2016-01-01

    Sudden cardiac death threats ischaemic and dilated cardiomyopathy patients. Anti- arrhythmic protection may be provided to these patients with implanted cardiac defibrillators(ICD), after an efficient risk stratification approach. The proposed risk stratifier of an impaired left ventricular ejection fraction has limited sensitivity meaning that a significant number of victims will remain undetectable by this risk stratification approach because they have a preserved left ventricular systolic function. Current risk stratification strategies focus on combinations of non invasive methods like T wave alternans, late potentials, heart rate turbulence, deceleration capacity and others, with invasive methods like the electrophysiologic study. In the presence of an electrically impaired substrate with formed post myocardial infarction fibrotic zones, programmed ventricular stimulation provides important prognostic information for the selection of the patients expected to benefit from an ICD implantation, while due to its high negative predictive value, patients at low risk level may also be detected. Clustering evidence from different research groups and electrophysiologic labs support an electrophysiologic testing guided risk stratification approach for sudden cardiac death.

  16. Mechanisms of electrical activation and conduction in the gastrointestinal system: lessons from cardiac electrophysiology

    Directory of Open Access Journals (Sweden)

    Gary eTse

    2016-05-01

    Full Text Available The gastrointestinal (GI tract is an electrically excitable organ system containing multiple cell types, which coordinate electrical activity propagating through this tract. Disruption in its normal electrophysiology is observed in a number of GI motility disorders. However, this is not well characterized and the field of GI electrophysiology is much less developed compared to the cardiac field. The aim of this article is to use the established knowledge of cardiac electrophysiology to shed light on the mechanisms of electrical activation and propagation along the GI tract, and how abnormalities in these processes lead to motility disorders and suggest better treatment options based on this improved understanding. In the first part of the article, the ionic contributions to the generation of GI slow wave and the cardiac action potential (AP are reviewed. Propagation of these electrical signals can be described by the core conductor theory in both systems. However, specifically for the GI tract, the following unique properties are observed: changes in slow wave frequency along its length, periods of quiescence, synchronization in short distances and desynchronization over long distances. These are best described by a coupled oscillator theory. Other differences include the diminished role of gap junctions in mediating this conduction in the GI tract compared to the heart. The electrophysiology of conditions such as gastroesophageal reflux disease and gastroparesis, and functional problems such as irritable bowel syndrome are discussed in detail, with reference to ion channel abnormalities and potential therapeutic targets. A deeper understanding of the molecular basis and physiological mechanisms underlying GI motility disorders will enable the development of better diagnostic and therapeutic tools and the advancement of this field.

  17. OptoDyCE: Automated system for high-throughput all-optical dynamic cardiac electrophysiology

    Science.gov (United States)

    Klimas, Aleksandra; Yu, Jinzhu; Ambrosi, Christina M.; Williams, John C.; Bien, Harold; Entcheva, Emilia

    2016-02-01

    In the last two decades, drugs withdrawals from the market were due to cardiac toxicity, where unintended interactions with ion channels disrupt the heart's normal electrical function. Consequently, all new drugs must undergo preclinical testing for cardiac liability, adding to an already expensive and lengthy process. Recognition that proarrhythmic effects often result from drug action on multiple ion channels demonstrates a need for integrative and comprehensive measurements. Additionally, patient-specific therapies relying on emerging technologies employing stem-cell derived cardiomyocytes (e.g. induced pluripotent stem-cell-derived cardiomyocytes, iPSC-CMs) require better screening methods to become practical. However, a high-throughput, cost-effective approach for cellular cardiac electrophysiology has not been feasible. Optical techniques for manipulation and recording provide a contactless means of dynamic, high-throughput testing of cells and tissues. Here, we consider the requirements for all-optical electrophysiology for drug testing, and we implement and validate OptoDyCE, a fully automated system for all-optical cardiac electrophysiology. We demonstrate the high-throughput capabilities using multicellular samples in 96-well format by combining optogenetic actuation with simultaneous fast high-resolution optical sensing of voltage or intracellular calcium. The system can also be implemented using iPSC-CMs and other cell-types by delivery of optogenetic drivers, or through the modular use of dedicated light-sensitive somatic cells in conjunction with non-modified cells. OptoDyCE provides a truly modular and dynamic screening system, capable of fully-automated acquisition of high-content information integral for improved discovery and development of new drugs and biologics, as well as providing a means of better understanding of electrical disturbances in the heart.

  18. Automated Electrophysiology Makes the Pace for Cardiac Ion Channel Safety Screening

    Directory of Open Access Journals (Sweden)

    Clemens eMoeller

    2011-11-01

    Full Text Available The field of automated patch-clamp electrophysiology has emerged from the tension between the pharmaceutical industry’s need for high-throughput compound screening versus its need to be conservative due to regulatory requirements. On the one hand, hERG channel screening was increasingly requested for new chemical entities, as the correlation between blockade of the ion channel coded by hERG and Torsades de Pointes cardiac arrhythmia gained increasing attention. On the other hand, manual patch-clamping, typically quoted as the gold-standard for understanding ion channel function and modulation, was far too slow (and, consequently, too expensive for keeping pace with the numbers of compounds submitted for hERG channel investigations from pharmaceutical R&D departments. In consequence it became more common for some pharmaceutical companies to outsource safety pharmacological investigations, with a focus on hERG channel interactions. This outsourcing has allowed those pharmaceutical companies to build up operational flexibility and greater independence from internal resources, and allowed them to obtain access to the latest technological developments that emerged in automated patch-clamp electrophysiology – much of which arose in specialized biotech companies. Assays for nearly all major cardiac ion channels are now available by automated patch-clamping using heterologous expression systems, and recently, automated action potential recordings from stem-cell derived cardiomyocytes have been demonstrated. Today, most of the large pharmaceutical companies have acquired automated electrophysiology robots and have established various automated cardiac ion channel safety screening assays on these, in addition to outsourcing parts of their needs for safety screening.

  19. Cardiac sodium channelopathy associated with SCN5A mutations: electrophysiological, molecular and genetic aspects.

    Science.gov (United States)

    Remme, Carol Ann

    2013-09-01

    Over the last two decades, an increasing number of SCN5A mutations have been described in patients with long QT syndrome type 3 (LQT3), Brugada syndrome, (progressive) conduction disease, sick sinus syndrome, atrial standstill, atrial fibrillation, dilated cardiomyopathy, and sudden infant death syndrome (SIDS). Combined genetic, electrophysiological and molecular studies have provided insight into the dysfunction and dysregulation of the cardiac sodium channel in the setting of SCN5A mutations identified in patients with these inherited arrhythmia syndromes. However, risk stratification and patient management is hindered by the reduced penetrance and variable disease expressivity in sodium channelopathies. Furthermore, various SCN5A-related arrhythmia syndromes are known to display mixed phenotypes known as cardiac sodium channel overlap syndromes. Determinants of variable disease expressivity, including genetic background and environmental factors, are suspected but still largely unknown. Moreover, it has become increasingly clear that sodium channel function and regulation is more complicated than previously assumed, and the sodium channel may play additional, as of yet unrecognized, roles in cardiac structure and function. Development of cardiac structural abnormalities secondary to SCN5A mutations has been reported, but the clinical relevance and underlying mechanisms are unclear. Increased insight into these issues would enable a major next step in research related to cardiac sodium channel disease, ultimately enabling improved diagnosis, risk stratification and treatment strategies.

  20. Simulation of cardiac electrophysiology on next-generation high-performance computers.

    Science.gov (United States)

    Bordas, Rafel; Carpentieri, Bruno; Fotia, Giorgio; Maggio, Fabio; Nobes, Ross; Pitt-Francis, Joe; Southern, James

    2009-05-28

    Models of cardiac electrophysiology consist of a system of partial differential equations (PDEs) coupled with a system of ordinary differential equations representing cell membrane dynamics. Current software to solve such models does not provide the required computational speed for practical applications. One reason for this is that little use is made of recent developments in adaptive numerical algorithms for solving systems of PDEs. Studies have suggested that a speedup of up to two orders of magnitude is possible by using adaptive methods. The challenge lies in the efficient implementation of adaptive algorithms on massively parallel computers. The finite-element (FE) method is often used in heart simulators as it can encapsulate the complex geometry and small-scale details of the human heart. An alternative is the spectral element (SE) method, a high-order technique that provides the flexibility and accuracy of FE, but with a reduced number of degrees of freedom. The feasibility of implementing a parallel SE algorithm based on fully unstructured all-hexahedra meshes is discussed. A major computational task is solution of the large algebraic system resulting from FE or SE discretization. Choice of linear solver and preconditioner has a substantial effect on efficiency. A fully parallel implementation based on dynamic partitioning that accounts for load balance, communication and data movement costs is required. Each of these methods must be implemented on next-generation supercomputers in order to realize the necessary speedup. The problems that this may cause, and some of the techniques that are beginning to be developed to overcome these issues, are described.

  1. Computational models of atrial cellular electrophysiology and calcium handling, and their role in atrial fibrillation.

    Science.gov (United States)

    Heijman, Jordi; Erfanian Abdoust, Pegah; Voigt, Niels; Nattel, Stanley; Dobrev, Dobromir

    2016-02-01

    The complexity of the heart makes an intuitive understanding of the relative contribution of ion channels, transporters and signalling pathways to cardiac electrophysiology challenging. Computational modelling of cardiac cellular electrophysiology has proven useful to integrate experimental findings, extrapolate results obtained in expression systems or animal models to other systems, test quantitatively ideas based on experimental data and provide novel hypotheses that are experimentally testable. While the bulk of computational modelling has traditionally been directed towards ventricular bioelectricity, increasing recognition of the clinical importance of atrial arrhythmias, particularly atrial fibrillation, has led to widespread efforts to apply computational approaches to understanding atrial electrical function. The increasing availability of detailed, atrial-specific experimental data has stimulated the development of novel computational models of atrial-cellular electrophysiology and Ca(2+) handling. To date, more than 300 studies have employed mathematical simulations to enhance our understanding of atrial electrophysiology, arrhythmogenesis and therapeutic responses. Future modelling studies are likely to move beyond current whole-cell models by incorporating new data on subcellular architecture, macromolecular protein complexes, and localized ion-channel regulation by signalling pathways. At the same time, more integrative multicellular models that take into account regional electrophysiological and Ca(2+) handling properties, mechano-electrical feedback and/or autonomic regulation will be needed to investigate the mechanisms governing atrial arrhythmias. A combined experimental and computational approach is expected to provide the more comprehensive understanding of atrial arrhythmogenesis that is required to develop improved diagnostic and therapeutic options. Here, we review this rapidly expanding area, with a particular focus on Ca(2+) handling, and

  2. Electrophysiological predictors of sudden cardiac death on physical exercise test in young athletes

    Science.gov (United States)

    Balykova, L. A.; Kotlyarov, A. A.; Ivyanskiy, S. A.; Shirokova, A. A.; Miheeva, K. A.; Makarov, L. M.

    2017-01-01

    The problem of sudden death of young athletes continues to be actual. Among its reasons, primary electric myocardium diseases along with organic heart troubles (cardiomyopathies, cordites, anomalies of coronary arteries) take an important place. The most frequent variant of channelopathesis long QT syndrome (LQTS). Both inherited and acquired LQTS may be the reason of sudden cardiac death during physical activity and have to be revealed prior to sports admission. LQTS diagnostics in young athletes become problematic due to secondary exercise-related QT prolongation. Physical load test may reveal myocardium electric instability and enhance LQTS diagnostics accuracy without genetic testing. The aim was to study electrophysiological parameters of myocardium repolarization and reveal the signs of electrical instability as predictors of the life-threatening arrhythmias in young athletes during physical exercise test. In conclusion, electrophysiological myocardium parameters during physical exercise test noted to be markers of electrical myocardial instability and in combination with the other Schwartz criteria, was evidenced the inherited or acquired LQTS. QTc prolongation in athletes at the peak of exercise as well as in early recovery period were noted to be additional predictor life-threatening arrhythmias and sudden cardiac death in young athletes

  3. Numerical quadrature and operator splitting in finite element methods for cardiac electrophysiology.

    Science.gov (United States)

    Krishnamoorthi, Shankarjee; Sarkar, Mainak; Klug, William S

    2013-11-01

    We study the numerical accuracy and computational efficiency of alternative formulations of the finite element solution procedure for the monodomain equations of cardiac electrophysiology, focusing on the interaction of spatial quadrature implementations with operator splitting and examining both nodal and Gauss quadrature methods and implementations that mix nodal storage of state variables with Gauss quadrature. We evaluate the performance of all possible combinations of 'lumped' approximations of consistent capacitance and mass matrices. Most generally, we find that quadrature schemes and lumped approximations that produce decoupled nodal ionic equations allow for the greatest computational efficiency, this being afforded through the use of asynchronous adaptive time-stepping of the ionic state variable ODEs. We identify two lumped approximation schemes that exhibit superior accuracy, rivaling that of the most expensive variationally consistent implementations. Finally, we illustrate some of the physiological consequences of discretization error in electrophysiological simulation relevant to cardiac arrhythmia and fibrillation. These results suggest caution with the use of semi-automated free-form tetrahedral and hexahedral meshing algorithms available in most commercially available meshing software, which produce nonuniform meshes having a large distribution of element sizes.

  4. Influence of acute stress on cardiac electrophysiological stability in male goats.

    Science.gov (United States)

    Liu, Jianguo; Wang, Yutang; Shan, Zhaoliang; Guo, Hongyang

    2012-06-01

    Stress plays an important role in the pathogenesis of ventricular arrhythmias. This study was designed to examine the effect of acute stress and metoprolol, a beta adrenergic receptor blocker, on cardiac electrophysiological stability of male goats. Fifteen male goats were randomly divided into three groups: (i) control animals (n=5), (ii) a compound stimuli group including noise and red flash (n=5), (iii) and a compound stimuli group with metoprolol treatment (n=5). Plasma catecholamines were determined by using high performance chromatography with electrochemical detection. Heart rate turbulence (HRT) and heart rate variability (HRV) were analysed with the MGY-H12L analysis system. Also, the ventricular fibrillation threshold (VFT) and the ventricular vulnerable period (VVP) were determined by programmed S1S2 stimulus with bipolar electrodes at the apex of the goat hearts. Compound stimuli increased plasma catecholamine levels progressively and decreased the negative value of turbulence onset (TO), turbulence slope (TS), SDNN, PNN50. Moreover, compound stimuli broadened VVP and decreased VFT significantly. Although metoprolol treatment failed to affect plasma catecholamine levels, TS and PNN50 value of the compound stimuli group, it significantly increased the negative value of TO, SDNN, VFT and narrowed VVP. Our data demonstrates that compound stimuli can induce acute stressful reactions, and decrease the cardiac electrophysiological stability of male goats, which can be counteracted by metoprolol treatment.

  5. Impact of KChIP2 on Cardiac Electrophysiology and the Progression of Heart Failure

    DEFF Research Database (Denmark)

    Grubb, Søren; Callø, Kirstine; Thomsen, Morten B

    2012-01-01

    Electrophysiological remodeling of cardiac potassium ion channels is important in the progression of heart failure. A reduction of the transient outward potassium current (I(to)) in mammalian heart failure is consistent with a reduced expression of potassium channel interacting protein 2 (KChIP2......, a K(V)4 subunit). Approaches have been made to investigate the role of KChIP2 in shaping cardiac I(to), including the use of transgenic KChIP2 deficient mice and viral overexpression of KChIP2. The interplay between I(to) and myocardial calcium handling is pivotal in the development of heart failure......, and is further strengthened by the dual role of KChIP2 as a functional subunit on both K(V)4 and Ca(V)1.2. Moreover, the potential arrhythmogenic consequence of reduced I(to) may contribute to the high relative incidence of sudden death in the early phases of human heart failure. With this review, we offer...

  6. Health technology assessment on reprocessing single-use catheters for cardiac electrophysiology: results of a three-years study.

    Science.gov (United States)

    Tessarolo, F; Disertori, M; Caola, I; Guarrera, G M; Favaretti, C; Nollo, G

    2007-01-01

    The study aims to define the technical, ethical, juridical and economic issues involved in the assessment of a reprocessing policy for single-use interventional cardiac devices (SUDs). The feasibility of reprocessing was evaluated for cardiac electrophysiology catheters by comparing the chemical, physical and functional properties of new and reprocessed devices. The issue of hygiene was addressed by developing microbiological tests for the quantification of bioburden, sterility and pyrogenic load. The results of more than 1500 tests, conducted on 531 catheters, suggested a precautionary number of regenerations of five cycles. The ethical aspects were reviewed and the European juridical framework was assessed, revealing a need for harmonization. Applying a specific economic model, potential savings were calculated for a representative cardiology department and estimated at national and European level. Potential savings of 41.2% and 32.9% were calculated for diagnostic and ablation catheters, respectively. Safe and effective reprocessing of SUDs could be pursued if quality control processes and certified procedures are met. A reprocessing policy in EP laboratory could lead to savings of about 27,250 euros per 100,000 population, but the economic benefits are strongly dependent on the maximum number of regenerations and the regeneration rate.

  7. NEWBORNS OF HIGH RISK GROUPS AND ELECTROPHYSIOLOGICAL CARDIAC ACTIVITY DURING THE PERIOD OF EARLY ADAPTATION

    Directory of Open Access Journals (Sweden)

    T. S. Tumaeva

    2014-01-01

    Full Text Available Aim: to study characteristics of electrophysiological cardiac activity in children of risk groups and to assess possibilities of Holter-electrocardiography (H-ECG in revealing of cardiac dysfunction during the period of early adaptation. Patients and methods: 250 newborns were examined. The main group consisted of 200 children with cerebral ischemia (CI. This group was divided into 2 subgroups: 100 full-term and 100 premature (at various gestation age infants. Control group contained 50 children born at 38–40th weeks of gestation with physiological course of pregnancy and delivery, APGAR score of 8–9 points. Complex examination included H-ECG according the standard technic with evaluation of the hearth rate (HR during sleep and wakefulness; HRmin, HRmax; arrhythmias, conductivity disorders, duration of the intervals; rhythm variability. Results: according to the ECG children with CI, especially premature ones, and children delivered via Cesarean section more often had ST-T disturbances, arrhythmias (sinus tachycardia, less often — sinus bradycardia and conductivity disorders, Q-Tc prolongation. H-EGC revealed decrease of sleep HR, HRmin and HRmax in children with CI especially in delivered via Cesarean section. The most common arrhythmia was supraventricular extrasystole.  Pauses in rhythms and variability were the highest in premature children delivered via Cesarean section. Conclusions: hypoxia/ischemia is a trigger for development of cardiovascular dysfuncion in newborns. Premature and children delivered via Cesarean section form a group of high risk. H-ECG widens possibilities of revealing of symptoms of cardiac dysfunction (disturbances at the basal level of functioning, of adaptation resources of the sinus node, electric instability of the myocardium and heart rate variability in children of risk group for development of cardiovascular disorders. 

  8. Effect of regional differences in cardiac cellular electrophysiology on the stability of ventricular arrhythmias: a computational study

    Science.gov (United States)

    Clayton, Richard H.; Holden, Arun V.

    2003-01-01

    Re-entry is an important mechanism of cardiac arrhythmias. During re-entry a wave of electrical activation repeatedly propagates into recovered tissue, rotating around a rod-like filament. Breakdown of a single re-entrant wave into multiple waves is believed to underlie the transition from ventricular tachycardia to ventricular fibrillation. Several mechanisms of breakup have been identified including the effect of anisotropic conduction in the ventricular wall. Cells in the inner and outer layers of the ventricular wall have different action potential durations (APD), and support re-entrant waves with different periods. The aim of this study was to use a computational approach to study twisting and breakdown in a transmural re-entrant wave spanning these regions, and examine the relative role of this effect and anisotropic conduction. We used a simplified model of action potential conduction in the ventricular wall that we modified so that it supported stable re-entry in an anisotropic model with uniform APD. We first examined the effect of regional differences on breakdown in an isotropic model with transmural differences in APD, and found that twisting of the re-entrant filament resulted in buckling and breakdown during the second cycle of re-entry. We found that breakdown was amplified in the anisotropic model, resulting in complex activation in the region of longest APD. This study shows that regional differences in cardiac electrophysiology are a potentially important mechanism for destabilizing re-entry and may act synergistically with other mechanisms to mediate the transition from ventricular tachycardia to ventricular fibrillation.

  9. Effect of regional differences in cardiac cellular electrophysiology on the stability of ventricular arrhythmias: a computational study

    Energy Technology Data Exchange (ETDEWEB)

    Clayton, Richard H; Holden, Arun V [School of Biomedical Sciences, University of Leeds, Woodhouse Lane, Leeds (United Kingdom)

    2003-01-07

    Re-entry is an important mechanism of cardiac arrhythmias. During re-entry a wave of electrical activation repeatedly propagates into recovered tissue, rotating around a rod-like filament. Breakdown of a single re-entrant wave into multiple waves is believed to underlie the transition from ventricular tachycardia to ventricular fibrillation. Several mechanisms of breakup have been identified including the effect of anisotropic conduction in the ventricular wall. Cells in the inner and outer layers of the ventricular wall have different action potential durations (APD), and support re-entrant waves with different periods. The aim of this study was to use a computational approach to study twisting and breakdown in a transmural re-entrant wave spanning these regions, and examine the relative role of this effect and anisotropic conduction. We used a simplified model of action potential conduction in the ventricular wall that we modified so that it supported stable re-entry in an anisotropic model with uniform APD. We first examined the effect of regional differences on breakdown in an isotropic model with transmural differences in APD, and found that twisting of the re-entrant filament resulted in buckling and breakdown during the second cycle of re-entry. We found that breakdown was amplified in the anisotropic model, resulting in complex activation in the region of longest APD. This study shows that regional differences in cardiac electrophysiology are a potentially important mechanism for destabilizing re-entry and may act synergistically with other mechanisms to mediate the transition from ventricular tachycardia to ventricular fibrillation.

  10. Comparison of electrophysiological effects of calcium channel blockers on cardiac repolarization.

    Science.gov (United States)

    Lee, Hyang-Ae; Hyun, Sung-Ae; Park, Sung-Gurl; Kim, Ki-Suk; Kim, Sung Joon

    2016-01-01

    Dihydropyridine (DHP) calcium channel blockers (CCBs) have been widely used to treat of several cardiovascular diseases. An excessive shortening of action potential duration (APD) due to the reduction of Ca(2+) channel current (I Ca) might increase the risk of arrhythmia. In this study we investigated the electrophysiological effects of nicardipine (NIC), isradipine (ISR), and amlodipine (AML) on the cardiac APD in rabbit Purkinje fibers, voltage-gated K(+) channel currents (I Kr, I Ks) and voltage-gated Na(+) channel current (I Na). The concentration-dependent inhibition of Ca(2+) channel currents (I Ca) was examined in rat cardiomyocytes; these CCBs have similar potency on I Ca channel blocking with IC50 (the half-maximum inhibiting concentration) values of 0.142, 0.229, and 0.227 nM on NIC, ISR, and AML, respectively. However, ISR shortened both APD50 and APD90 already at 1 µM whereas NIC and AML shortened APD50 but not APD90 up to 30 µM. According to ion channel studies, NIC and AML concentration-dependently inhibited I Kr and I Ks while ISR had only partial inhibitory effects (NIC and AML could compensate for the AP shortening effects due to the block of I Ca.

  11. Electrophysiological effects of the new cardioactive drug CERM 4205: a comparative study in an animal model and in man.

    Science.gov (United States)

    Brugada, J; Lamar, J C; Boisson, P; Masse, C; Puech, P; Sassine, A

    1988-01-01

    The cardiac electrophysiological effects of CERM 4205, a new cardioactive agent, were studied by means of intracardiac electrodes in man and in anaesthetized dogs. The results show that CERM 4205 is a cardioactive drug with a main inhibitory effect on slow-response structures (sinus and atrioventricular node) with an associated effect on fast-response structures (atrial, His-Purkinje and ventricular tissues). No qualitative differences were observed between the effects observed in man and dogs. In conclusion, the present study confirms that CERM 4205 is a compound with combined class IV and class I electrophysiological effects in dogs and man. The anaesthetized dog appears to be a satisfactory model for the evaluation of the electrophysiological effects of cardioactive drugs.

  12. Automatic fitting of spiking neuron models to electrophysiological recordings

    Directory of Open Access Journals (Sweden)

    Cyrille Rossant

    2010-03-01

    Full Text Available Spiking models can accurately predict the spike trains produced by cortical neurons in response to somatically injected currents. Since the specific characteristics of the model depend on the neuron, a computational method is required to fit models to electrophysiological recordings. The fitting procedure can be very time consuming both in terms of computer simulations and in terms of code writing. We present algorithms to fit spiking models to electrophysiological data (time-varying input and spike trains that can run in parallel on graphics processing units (GPUs. The model fitting library is interfaced with Brian, a neural network simulator in Python. If a GPU is present it uses just-in-time compilation to translate model equations into optimized code. Arbitrary models can then be defined at script level and run on the graphics card. This tool can be used to obtain empirically validated spiking models of neurons in various systems. We demonstrate its use on public data from the INCF Quantitative Single-Neuron Modeling 2009 competition by comparing the performance of a number of neuron spiking models.

  13. Implementation of Contraction to Electrophysiological Ventricular Myocyte Models, and Their Quantitative Characterization via Post-Extrasystolic Potentiation.

    Science.gov (United States)

    Ji, Yanyan Claire; Gray, Richard A; Fenton, Flavio H

    2015-01-01

    Heart failure (HF) affects over 5 million Americans and is characterized by impairment of cellular cardiac contractile function resulting in reduced ejection fraction in patients. Electrical stimulation such as cardiac resynchronization therapy (CRT) and cardiac contractility modulation (CCM) have shown some success in treating patients with HF. Computer simulations have the potential to help improve such therapy (e.g. suggest optimal lead placement) as well as provide insight into the underlying mechanisms which could be beneficial. However, these myocyte models require a quantitatively accurate excitation-contraction coupling such that the electrical and contraction predictions are correct. While currently there are close to a hundred models describing the detailed electrophysiology of cardiac cells, the majority of cell models do not include the equations to reproduce contractile force or they have been added ad hoc. Here we present a systematic methodology to couple first generation contraction models into electrophysiological models via intracellular calcium and then compare the resulting model predictions to experimental data. This is done by using a post-extrasystolic pacing protocol, which captures essential dynamics of contractile forces. We found that modeling the dynamic intracellular calcium buffers is necessary in order to reproduce the experimental data. Furthermore, we demonstrate that in models the mechanism of the post-extrasystolic potentiation is highly dependent on the calcium released from the Sarcoplasmic Reticulum. Overall this study provides new insights into both specific and general determinants of cellular contractile force and provides a framework for incorporating contraction into electrophysiological models, both of which will be necessary to develop reliable simulations to optimize electrical therapies for HF.

  14. Comparison of Ventricular Electrophysiological Effects of Amiodarone in Canine Models With Congestive Heart Failure and Normal Dogs

    Institute of Scientific and Technical Information of China (English)

    Shuxian Zhou; Yuling Zhang; Juan Lei; Wei Wu; Xuming Zhang

    2008-01-01

    Objectives This study compared the effects of amiodarone on ventricular electrophysiological properties in normal dogs and CHF dogs.Methods Dogs(n=44) were randomized into four groups:Group 1(n=10)was the control.Group 2(n=10) was given amiodarone orally 300 mg·d-1 for4 to 5 weeks.Group 3(n=12)was the congestive heart failure(CHF)models induced by right ventricular rapid pacing(240 pulses·rain-1 for 4 to 5 weeks).Group 4 (n=12) was the CHF models given amiodarone orally 300 mg·d-1 for 4 to 5 weeks.The ventricular electrophysiological variables were evaluated by standard electric stimulation and monophasic action potential(MAP)recording.Results Amiodarone prolonged sinus cycle length(SCL),intra-ventricular conduction time(IVCT),MAP duration(MAPD90),ventricular effective period(VERP),ventricular activation time(VAT)and ventficular recovery time(VRT)without significant effects on the ratio of VERP to MAPD90 (VERP/MAPD90),ventricular fibrillation threshold(VFT),the dispersion of VRT(VRTD),and ventricular late repolarization duration(VLRD)in normal dogs.However,amiodarone did not further prolong the prolonged SCL,MAPD90,VERP,VAT and VRT,but further prolonged IVCT in CHF dogs.Amiodarone normalized the abnormal ventficular electrophysiological properties in CHF dogs as manifested by increasing the decreased VERP/MAPD90 and VFT,shortening the prolonged VLRD,and decreasing the increased VRTD.Amiodarone did not worsen the hemodynamic parameters in normal and CHF dogs.Conclusions Amiodarone had different effects on ventricular electrophysiological properties in normal and CHF dogs.The favorable effects of amiodarone in normalizing some abnormal cardiac electrophysiological properties in CHF models may have potential value on the prevention and treatment of ventricular arrhythmias and sudden cardiac death in CHF.

  15. Real-time x-ray fluoroscopy-based catheter detection and tracking for cardiac electrophysiology interventions

    Energy Technology Data Exchange (ETDEWEB)

    Ma Yingliang; Housden, R. James; Razavi, Reza; Rhode, Kawal S. [Division of Imaging Sciences and Biomedical Engineering, King' s College London, London SE1 7EH (United Kingdom); Gogin, Nicolas; Cathier, Pascal [Medisys Research Group, Philips Healthcare, Paris 92156 (France); Gijsbers, Geert [Interventional X-ray, Philips Healthcare, Best 5680 DA (Netherlands); Cooklin, Michael; O' Neill, Mark; Gill, Jaswinder; Rinaldi, C. Aldo [Department of Cardiology, Guys and St. Thomas' Hospitals NHS Foundation Trust, London SE1 7EH (United Kingdom)

    2013-07-15

    Purpose: X-ray fluoroscopically guided cardiac electrophysiology (EP) procedures are commonly carried out to treat patients with arrhythmias. X-ray images have poor soft tissue contrast and, for this reason, overlay of a three-dimensional (3D) roadmap derived from preprocedural volumetric images can be used to add anatomical information. It is useful to know the position of the catheter electrodes relative to the cardiac anatomy, for example, to record ablation therapy locations during atrial fibrillation therapy. Also, the electrode positions of the coronary sinus (CS) catheter or lasso catheter can be used for road map motion correction.Methods: In this paper, the authors present a novel unified computational framework for image-based catheter detection and tracking without any user interaction. The proposed framework includes fast blob detection, shape-constrained searching and model-based detection. In addition, catheter tracking methods were designed based on the customized catheter models input from the detection method. Three real-time detection and tracking methods are derived from the computational framework to detect or track the three most common types of catheters in EP procedures: the ablation catheter, the CS catheter, and the lasso catheter. Since the proposed methods use the same blob detection method to extract key information from x-ray images, the ablation, CS, and lasso catheters can be detected and tracked simultaneously in real-time.Results: The catheter detection methods were tested on 105 different clinical fluoroscopy sequences taken from 31 clinical procedures. Two-dimensional (2D) detection errors of 0.50 {+-} 0.29, 0.92 {+-} 0.61, and 0.63 {+-} 0.45 mm as well as success rates of 99.4%, 97.2%, and 88.9% were achieved for the CS catheter, ablation catheter, and lasso catheter, respectively. With the tracking method, accuracies were increased to 0.45 {+-} 0.28, 0.64 {+-} 0.37, and 0.53 {+-} 0.38 mm and success rates increased to 100%, 99

  16. A numerical guide to the solution of the bidomain equations of cardiac electrophysiology

    KAUST Repository

    Pathmanathan, Pras

    2010-06-01

    Simulation of cardiac electrical activity using the bidomain equations can be a massively computationally demanding problem. This study provides a comprehensive guide to numerical bidomain modelling. Each component of bidomain simulations-discretisation, ODE-solution, linear system solution, and parallelisation-is discussed, and previously-used methods are reviewed, new methods are proposed, and issues which cause particular difficulty are highlighted. Particular attention is paid to the choice of stimulus currents, compatibility conditions for the equations, the solution of singular linear systems, and convergence of the numerical scheme. © 2010 Elsevier Ltd.

  17. Reversal of bupivacaine-induced cardiac electrophysiologic changes by two lipid emulsions in anesthetized and mechanically ventilated piglets.

    Science.gov (United States)

    Candela, Damien; Louart, Guillaume; Bousquet, Philippe-Jean; Muller, Laurent; Nguyen, Micheline; Boyer, Jean-Christophe; Peray, Pascale A Fabbro; Goret, Lucie; Ripart, Jacques; Lefrant, Jean-Yves; de La Coussaye, Jean E

    2010-05-01

    Accidental IV administration of bupivacaine can compromise cardiovascular function by inducing lethal arrhythmias whose hemodynamic consequences may be alleviated by lipid emulsions. However, little is known about the electrophysiologic effects of lipid emulsions. In this study, we assessed whether 2 different lipid emulsions can reverse cardiac electrophysiologic impairment induced by the IV administration of bupivacaine in anesthetized and mechanically ventilated piglets. Bupivacaine (4 mg . kg(-1)) was injected over a 30-second period in 26 piglets. Thirty seconds after the end of bupivacaine injection, 1.5 mL . kg(-1) saline solution for the control group, and long-chain triglyceride emulsion (LCT group) or a mixture of long-chain and medium-chain triglyceride emulsion (LCT/MCT group) were infused over 1 minute. Cardiac conduction variables and hemodynamic variables were monitored for 30 minutes after injection. Bupivacaine induced similar electrophysiologic and hemodynamic changes. After 3 minutes, His ventricle intervals (median and interquartiles) were 100 (85-105), 45 (35-55), and 53 (48-73) milliseconds in the control, LCT, and LCT/MCT groups, respectively (P < 0.001 between control and both lipid emulsion groups). Lipid emulsions also reversed the effects on QRS duration, atrial-His, and PQ (the onset of the P wave to the Q wave of the QRS complex) intervals. LCT/MCT emulsion restored the decrease in maximal first derivative of left ventricular pressure (P < 0.01 after 3 minutes versus control group). LCT and LCT/MCT emulsions reversed the lengthening of His ventricle, QRS, atrial-His, and PQ intervals induced by the IV injection of 4 mg . kg(-1) bupivacaine.

  18. Does electrophysiological testing have any role in risk stratification for sudden cardiac death?

    Institute of Scientific and Technical Information of China (English)

    Fei Lü; Wei Hua

    2010-01-01

    @@ Introduction Implantation of implantable cardioverter defibrillators (ICD) has widely been accepted for secondary prevention of sudden cardiac death (SCD) in cardiac arrest survivors.1 Currently there are increasing interests in primary prevention of SCD in selected high risk patients who have not experienced cardiac arrest.1

  19. Accelerating mono-domain cardiac electrophysiology simulations using OpenCL

    Directory of Open Access Journals (Sweden)

    Wülfers Eike M.

    2015-09-01

    Full Text Available Using OpenCL, we developed a cross-platform software to compute electrical excitation conduction in cardiac tissue. OpenCL allowed the software to run parallelized and on different computing devices (e.g., CPUs and GPUs. We used the macroscopic mono-domain model for excitation conduction and an atrial myocyte model by Courtemanche et al. for ionic currents. On a CPU with 12 HyperThreading-enabled Intel Xeon 2.7 GHz cores, we achieved a speed-up of simulations by a factor of 1.6 against existing software that uses OpenMPI. On two high-end AMD FirePro D700 GPUs the OpenCL software ran 2.4 times faster than the OpenMPI implementation. The more nodes the discretized simulation domain contained, the higher speed-ups were achieved.

  20. Diverse toxicity associated with cardiac Na+/K+ pump inhibition: evaluation of electrophysiological mechanisms.

    Science.gov (United States)

    Rocchetti, M; Besana, A; Mostacciuolo, G; Ferrari, P; Micheletti, R; Zaza, A

    2003-05-01

    (E,Z)-3-((2-Aminoethoxy)imino)androstane-6,17-dione hydrochloride (PST2744) is a novel Na(+)/K(+) pump inhibitor with positive inotropic effects. Compared with digoxin in various experimental models, PST2744 was consistently found to be less arrhythmogenic, thus resulting in a significantly higher therapeutic index. The present work compares the electrophysiological effects of PST2744 and digoxin in guinea pig ventricular myocytes, with the aim to identify a mechanism for their different toxicity. The work showed that 1) the action potential was transiently prolonged and then similarly shortened by both agents; 2) the ratio between Na(+)/K(+) pump inhibition and inotropy was somewhat larger for PST2744 than for digoxin; 3) both agents accelerated inactivation of high-threshold Ca(2+) current (I(CaL)), without affecting its peak amplitude; 4) the transient inward current (I(TI)) induced by a Ca(2+) transient in the presence of complete Na(+)/K(+) pump blockade was inhibited (-43%) by PST2744 but not by digoxin; 5) the conductance of Na(+)/Ca(2+) exchanger current (I(NaCa)), recorded under Na(+)/K(+) pump blockade, was only slightly inhibited by PST2744 (-14%) and unaffected by digoxin; and 6) both agents inhibited delayed rectifier current I(Ks) (

  1. Coupled personalisation of electrophysiology models for simulation of induced ischemic ventricular tachycardia.

    Science.gov (United States)

    Relan, J; Chinchapatnam, P; Sermesant, M; Rhode, K; Delingette, H; Razavi, R; Ayache, N

    2010-01-01

    Despite recent efforts in cardiac electrophysiology modelling, there is still a strong need to make macroscopic models usable in planning and assistance of the clinical procedures. This requires model personalisation i.e. estimation of patient-specific model parameters and computations compatible with clinical constraints. Fast macroscopic models allow a quick estimation of the tissue conductivity, but are often unreliable in prediction of arrhythmias. On the other side, complex biophysical models are quite expensive for the tissue conductivity estimation, but are well suited for arrhythmia predictions. Here we present a coupled personalisation framework, which combines the benefits of the two models. A fast Eikonal (EK) model is used to estimate the conductivity parameters, which are then used to set the parameters of a biophysical model, the Mitchell-Schaeffer (MS) model. Additional parameters related to Action Potential Duration (APD) and APD restitution curves for the tissue are estimated for the MS model. This framework is applied to a clinical dataset provided with an hybrid X-Ray/MR imaging on an ischemic patient. This personalised MS Model is then used for in silico simulation of clinical Ventricular Tachycardia (VT) stimulation protocol to predict the induction of VT. This proof of concept opens up possibilities of using VT induction modelling directly in the intervention room, in order to plan the radio-frequency ablation lines.

  2. Behavioural, modeling, and electrophysiological evidence for supramodality in human metacognition.

    Science.gov (United States)

    Faivre, Nathan; Filevich, Elisa; Solovey, Guillermo; Kühn, Simone; Blanke, Olaf

    2017-09-15

    Human metacognition, or the capacity to introspect on one's own mental states, has been mostly characterized through confidence reports in visual tasks. A pressing question is to what extent results from visual studies generalize to other domains. Answering this question allows determining whether metacognition operates through shared, supramodal mechanisms, or through idiosyncratic, modality-specific mechanisms. Here, we report three new lines of evidence for decisional and post-decisional mechanisms arguing for the supramodality of metacognition. First, metacognitive efficiency correlated between auditory, tactile, visual, and audiovisual tasks. Second, confidence in an audiovisual task was best modeled using supramodal formats based on integrated representations of auditory and visual signals. Third, confidence in correct responses involved similar electrophysiological markers for visual and audiovisual tasks that are associated with motor preparation preceding the perceptual judgment. We conclude that the supramodality of metacognition relies on supramodal confidence estimates and decisional signals that are shared across sensory modalities.SIGNIFICANCE STATEMENTMetacognitive monitoring is the capacity to access, report and regulate one's own mental states. In perception, this allows rating our confidence in what we have seen, heard or touched. While metacognitive monitoring can operate on different cognitive domains, we ignore whether it involves a single supramodal mechanism common to multiple cognitive domains, or modality-specific mechanisms idiosyncratic to each domain. Here, we bring evidence in favor of the supramodality hypothesis by showing that participants with high metacognitive performance in one modality are likely to perform well in other modalities. Based on computational modeling and electrophysiology, we propose that supramodality can be explained by the existence of supramodal confidence estimates, and by the influence of decisional cues on

  3. Relationships between cardiac innervation/perfusion imbalance and ventricular arrhythmias: impact on invasive electrophysiological parameters and ablation procedures

    Energy Technology Data Exchange (ETDEWEB)

    Gimelli, Alessia [Fondazione Toscana Gabriele Monasterio, Pisa (Italy); Menichetti, Francesca; Soldati, Ezio; Liga, Riccardo; Vannozzi, Andrea; Bongiorni, Maria Grazia [University Hospital of Pisa, Cardio-Thoracic and Vascular Department, Pisa (Italy); Marzullo, Paolo [Fondazione Toscana Gabriele Monasterio, Pisa (Italy); CNR, Institute of Clinical Physiology, Pisa (Italy)

    2016-12-15

    To assess the relationship between regional myocardial perfusion and sympathetic innervation parameters at myocardial scintigraphy and intra-cavitary electrophysiological data in patients with ventricular arrhythmias (VA) submitted to invasive electrophysiological study and ablation procedure. Sixteen subjects underwent invasive electrophysiological study with electroanatomical mapping (EAM) followed by trans-catheter ablations of VA. Before ablation all patients were studied with a combined evaluation of regional myocardial perfusion and sympathetic innervation by means of tomographic {sup 99m}Tc-tetrofosmin and {sup 123}I- metaiodobenzylguanidine cadmium-zinc-telluride (CZT) scintigraphies, respectively. Off-line spatial co-registration of CZT perfusion and innervation data with the three-dimensional EAM reconstruction was performed in every patient. CZT revealed the presence of myocardial scar in 55 (20 %) segments. Of the viable myocardial segments, 131 (60 %) presented a preserved adrenergic innervation, while 86 (40 %) showed a significantly depressed innervation (i.e. innervation/perfusion mismatch). On EAM, the invasively measured intra-cavitary voltage was significantly lower in scarred segments than in viable ones (1.7 ± 1.5 mV vs. 4.0 ± 2.2 mV, P < 0.001). Interestingly, among the viable segments, those showing an innervation/perfusion mismatch presented a significantly lower intra-cavitary voltage than those with preserved innervation (1.9 ± 2.5 mV vs. 4.7 ± 2.3 mV, P < 0.001). Intra-cardiac ablation was performed in 63 (23 %) segments. On multivariate analysis, after correction for scar burden, the segments showing an innervation/perfusion mismatch remained the most frequent ablation targets (OR 5.6, 95 % CI 1.5-20.8; P = 0.009). In patients with VA, intra-cavitary electrical abnormalities frequently originate at the level of viable myocardial segments with depressed sympathetic innervation that frequently represents the ultimate ablation target

  4. Cardiac Electromechanical Models: From Cell to Organ

    Directory of Open Access Journals (Sweden)

    Natalia A Trayanova

    2011-08-01

    Full Text Available The heart is a multiphysics and multiscale system that has driven the development of the most sophisticated mathematical models at the frontiers of computation physiology and medicine. This review focuses on electromechanical (EM models of the heart from the molecular level of myofilaments to anatomical models of the organ. Because of the coupling in terms of function and emergent behaviors at each level of biological hierarchy, separation of behaviors at a given scale is difficult. Here, a separation is drawn at the cell level so that the first half addresses subcellular/single cell models and the second half addresses organ models. At the subcelluar level, myofilament models represent actin-myosin interaction and Ca-based activation. Myofilament models and their refinements represent an overview of the development in the field. The discussion of specific models emphasizes the roles of cooperative mechanisms and sarcomere length dependence of contraction force, considered the cellular basis of the Frank-Starling law. A model of electrophysiology and Ca handling can be coupled to a myofilament model to produce an EM cell model, and representative examples are summarized to provide an overview of the progression of field. The second half of the review covers organ-level models that require solution of the electrical component as a reaction-diffusion system and the mechanical component, in which active tension generated by the myocytes produces deformation of the organ as described by the equations of continuum mechanics. As outlined in the review, different organ-level models have chosen to use different ionic and myofilament models depending on the specific application; this choice has been largely dictated by compromises between model complexity and computational tractability. The review also addresses application areas of EM models such as cardiac resynchronization therapy and the role of mechano-electric coupling in arrhythmias and

  5. Integrative systems models of cardiac excitation-contraction coupling.

    Science.gov (United States)

    Greenstein, Joseph L; Winslow, Raimond L

    2011-01-07

    Excitation-contraction coupling in the cardiac myocyte is mediated by a number of highly integrated mechanisms of intracellular Ca²(+) transport. The complexity and integrative nature of heart cell electrophysiology and Ca²(+) cycling has led to an evolution of computational models that have played a crucial role in shaping our understanding of heart function. An important emerging theme in systems biology is that the detailed nature of local signaling events, such as those that occur in the cardiac dyad, have important consequences at higher biological scales. Multiscale modeling techniques have revealed many mechanistic links between microscale events, such as Ca²(+) binding to a channel protein, and macroscale phenomena, such as excitation-contraction coupling gain. Here, we review experimentally based multiscale computational models of excitation-contraction coupling and the insights that have been gained through their application.

  6. Sudden cardiac death and inherited channelopathy: the basic electrophysiology of the myocyte and myocardium in ion channel disease.

    Science.gov (United States)

    Martin, Claire A; Matthews, Gareth D K; Huang, Christopher L-H

    2012-04-01

    Mutations involving cardiac ion channels result in abnormal action potential formation or propagation, leading to cardiac arrhythmias. Despite the large impact on society of sudden cardiac death resulting from such arrhythmias, understanding of the underlying cellular mechanism is poor and clinical risk stratification and treatment consequently limited. Basic research using molecular techniques, as well as animal models, has proved extremely useful in improving our knowledge of inherited arrhythmogenic syndromes. This offers the practitioner tools to accurately diagnose rare disorders and provides novel markers for risk assessment and a basis for new strategies of treatment.

  7. Trpm4 Gene Invalidation Leads to Cardiac Hypertrophy and Electrophysiological Alterations

    Science.gov (United States)

    Gueffier, Mélanie; Finan, Amanda; Khoueiry, Ziad; Cassan, Cécile; Serafini, Nicolas; Aimond, Franck; Granier, Mathieu; Pasquié, Jean-Luc; Launay, Pierre; Richard, Sylvain

    2014-01-01

    Rationale TRPM4 is a non-selective Ca2+-activated cation channel expressed in the heart, particularly in the atria or conduction tissue. Mutations in the Trpm4 gene were recently associated with several human conduction disorders such as Brugada syndrome. TRPM4 channel has also been implicated at the ventricular level, in inotropism or in arrhythmia genesis due to stresses such as ß-adrenergic stimulation, ischemia-reperfusion, and hypoxia re-oxygenation. However, the physiological role of the TRPM4 channel in the healthy heart remains unclear. Objectives We aimed to investigate the role of the TRPM4 channel on whole cardiac function with a Trpm4 gene knock-out mouse (Trpm4-/-) model. Methods and Results Morpho-functional analysis revealed left ventricular (LV) eccentric hypertrophy in Trpm4-/- mice, with an increase in both wall thickness and chamber size in the adult mouse (aged 32 weeks) when compared to Trpm4+/+ littermate controls. Immunofluorescence on frozen heart cryosections and qPCR analysis showed no fibrosis or cellular hypertrophy. Instead, cardiomyocytes in Trpm4-/- mice were smaller than Trpm4+/+with a higher density. Immunofluorescent labeling for phospho-histone H3, a mitosis marker, showed that the number of mitotic myocytes was increased 3-fold in the Trpm4-/-neonatal stage, suggesting hyperplasia. Adult Trpm4-/- mice presented multilevel conduction blocks, as attested by PR and QRS lengthening in surface ECGs and confirmed by intracardiac exploration. Trpm4-/-mice also exhibited Luciani-Wenckebach atrioventricular blocks, which were reduced following atropine infusion, suggesting paroxysmal parasympathetic overdrive. In addition, Trpm4-/- mice exhibited shorter action potentials in atrial cells. This shortening was unrelated to modifications of the voltage-gated Ca2+ or K+ currents involved in the repolarizing phase. Conclusions TRPM4 has pleiotropic roles in the heart, including the regulation of conduction and cellular electrical activity

  8. Molecular Modeling of Cardiac Troponin

    Science.gov (United States)

    Manning, Edward P.

    The cardiac thin filament regulates interactions of actin and myosin, the force-generating elements of muscular contraction. Over the past several decades many details have been discovered regarding the structure and function of the cardiac thin filament and its components, including cardiac troponin (cTn). My hypothesis is that signal propagation occurs between distant ends of the cardiac troponin complex through calcium-dependent alterations in the dynamics of cTn and tropomyosin (Tm). I propose a model of the thin filament that encompasses known structures of cTn, Tm and actin to gain insight into cardiac troponin's allosteric regulation of thin filament dynamics. By performing molecular dynamics simulations of cTn in conjunction with overlapping Tm in two conditions, with and without calcium bound to site II of cardiac troponin C (cTnC), I found a combination of calcium-dependent changes in secondary structure and dynamics throughout the cTn-Tm complex. I then applied this model to investigate familial hypertrophic cardiomyopathy (FHC), a disease of the sarcomere that is one of the most commonly occurring genetic causes of heart disease. Approximately 15% of known FHC-related mutations are found in cardiac troponin T (cTnT), most of which are in or flank the alpha-helical N-tail domain TNT1. TNT1 directly interacts with overlapping Tm coiled coils. Using this model I identified effects of TNT1 mutations that propagate to the cTn core where site II of cTnC, the regulatory site of calcium binding in the thin filament, is located. Specifically, I found that mutations in TNT1 alter the flexibility of TNT1 and that the flexibility of TNT1 is inversely proportional to the cooperativity of calcium activation of the thin filament. Further, I identified a pathway of propagation of structural and dynamic changes linking TNT1 to site II of cTnC. Mutation-induced changes at site II cTnC alter calcium coordination which corresponds to biophysical measurements of calcium

  9. 家兔高钾血症心电生理机制的实验研究%The experimental research of cardiac electrophysiological mechanisms of hyperkalemia in rabbit

    Institute of Scientific and Technical Information of China (English)

    姜恒; 刘鸿

    2012-01-01

    Objective To study the toxic mechanisms of hyperkalemia on the heart in rabbit,by observing the cardiac electrophysiologi-cal characteristics of hyperkalemia in rabbit. Methods Record the normal ECG characteristics and serum potassium concentration in rabbit, then copy hyperkalemia model by the infusion of 1% ,4% ,10% KC1 solution ( 2 mL/kg ),observe the changes of cardiac electrophysiology characteristics in rabbit,record serum potassium concentration,absorbance,heart rate,abnormal rate of ECG and the change in the relationship between the various indicators before and after the injection of potassium solution. Results The change of the serum potassium concentration, absorbance, heart rate,abnormal rate of ECG,the period and amplitude of ECG waveform in the relationship between the various indicators in the experimental groups were significant variation ( P 0. 05 ). There is a high correlation between serum potassium and abnormal rate of ECG ( P 0.05),血钾浓度与心电图变异率高度相关(P0.05).结论 实验家兔高钾血症心电生理机制的研究对临床急性高钾血症的鉴别诊断、及时治疗有重要参考价值.

  10. Cardiac electrophysiological characteristics after transplantation of differentiated bone marrow mesenchymal stem cells%诱导骨髓间充质干细胞分化移植后的心脏电生理特性

    Institute of Scientific and Technical Information of China (English)

    刘博武; 吕安林; 燕学波; 黄炜; 候婧; 李垚

    2011-01-01

    BACKGROUND: With the development of biotechnology, the electrophysiology of repairing heart tissues of myocardial infarction or myocardial hypertrophy by using bone marrow mesenchymal stem cell has become a hot spot. OBJECTIVE: To overview the research progress of cardiac electrophysiological characteristics after transplantation of induced differentiation of bone marrow mesenchymal stem cells into cardiomyocytes. METHODS: The databases of PubMed, Springer Link, Science Direct and CNKI were retrieved for papers published from January 2000 to October 2010 with the key words of "bone marrow mesenchymal stem cells, cardiac/heart, electrophysiology/electrophysiological characteristics". The relevant articles concerning cardiac electrophysiological characteristics of induce differentiation and transplantation of bone marrow stem cells were collected. RESULTS AND CONCLUSION: Totally 208 papers have been searched. Preliminary screening by reading abstracts to exclude 162 papers that study purpose do not coincident with this review either contents duplicated, and internalized 46 papers at last. Bone marrow mesenchymal stem cells after induced differentiation and transplantation could improve heart function of animal experimental model and myocardial infarction or myocardial hypertrophy patients. Although the cardiomyocyte-like cells from bone marrow mesenchymal stem cells could help to improve heart function, the cardiac electrophysiological characteristics may be influenced by them.%背景:随着生物技术的发展,使用骨髓间充质干细胞修复心肌梗死后或者心肌肥厚心肌组织的电生理学成为当今研究热点.目的:概述骨髓间充质干细胞向心肌细胞诱导分化移植后的电生理特征的研究进展.方法:应用计算机检索PubMed数据库,Springer Link数据库,Science Direct数据库,CNKI数据库2000-01/2010-10文献,检索词分别为"bone marrow mesenchymal stem cells,cardiac/heart,electrophysiology/ electrophysiological

  11. Electrophysiological properties of inferior olive neurons: A compartmental model.

    Science.gov (United States)

    Schweighofer, N; Doya, K; Kawato, M

    1999-08-01

    As a step in exploring the functions of the inferior olive, we constructed a biophysical model of the olivary neurons to examine their unique electrophysiological properties. The model consists of two compartments to represent the known distribution of ionic currents across the cell membrane, as well as the dendritic location of the gap junctions and synaptic inputs. The somatic compartment includes a low-threshold calcium current (I(Ca_l)), an anomalous inward rectifier current (I(h)), a sodium current (I(Na)), and a delayed rectifier potassium current (I(K_dr)). The dendritic compartment contains a high-threshold calcium current (I(Ca_h)), a calcium-dependent potassium current (I(K_Ca)), and a current flowing into other cells through electrical coupling (I(c)). First, kinetic parameters for these currents were set according to previously reported experimental data. Next, the remaining free parameters were determined to account for both static and spiking properties of single olivary neurons in vitro. We then performed a series of simulated pharmacological experiments using bifurcation analysis and extensive two-parameter searches. Consistent with previous studies, we quantitatively demonstrated the major role of I(Ca_l) in spiking excitability. In addition, I(h) had an important modulatory role in the spike generation and period of oscillations, as previously suggested by Bal and McCormick. Finally, we investigated the role of electrical coupling in two coupled spiking cells. Depending on the coupling strength, the hyperpolarization level, and the I(Ca_l) and I(h) modulation, the coupled cells had four different synchronization modes: the cells could be in-phase, phase-shifted, or anti-phase or could exhibit a complex desynchronized spiking mode. Hence these simulation results support the counterintuitive hypothesis that electrical coupling can desynchronize coupled inferior olive cells.

  12. The Electrophysiological Effects of Qiliqiangxin on Cardiac Ventricular Myocytes of Rats

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    Yidong Wei

    2013-01-01

    Full Text Available Qiliqiangxin, a Chinese herb, represents the affection in Ca channel function of cardiac myocytes. It is unknown whether Qiliqiangxin has an effect on Na current and K current because the pharmacological actions of this herb’s compound are very complex. We investigated the rational usage of Qiliqiangxin on cardiac ventricular myocytes of rats. Ventricular myocytes were exposed acutely to 1, 10, and 50 mg/L Qiliqiangxin, and whole cell patch-clamp technique was used to study the acute effects of Qiliqiangxin on Sodium current (INa, outward currents delayed rectifier outward K+ current (IK, slowly activating delayed rectifier outward K+ current (IKs, transient outward K+ current (Ito, and inward rectifier K+ current (IK1. Qiliqiangxin can decrease INa by 28.53%±5.98%, and its IC50 was 9.2 mg/L. 10 and 50 mg/L Qiliqiangxin decreased by 37.2%±6.4% and 55.9%±5.5% summit current density of Ito. 10 and 50 mg/L Qiliqiangxin decreased IKs by 15.51%±4.03% and 21.6%±5.6%. Qiliqiangxin represented a multifaceted pharmacological profile. The effects of Qiliqiangxin on Na and K currents of ventricular myocytes were more profitable in antiarrhythmic therapy in the clinic. We concluded that the relative efficacy of Qiliqiangxin was another choice for the existing antiarrhythmic therapy.

  13. Implant evaluation of an insertable cardiac monitor outside the electrophysiology lab setting.

    Directory of Open Access Journals (Sweden)

    Roman Pachulski

    Full Text Available BACKGROUND: To date, insertable cardiac monitors (ICM have been implanted in the hospital without critical evaluation of other potential settings. Providing alternatives to in-hospital insertion may increase access to ICM, decrease waiting times for patients awaiting diagnosis, and reduce hospital resources. METHODS: This was a prospective, non-randomized, clinical trial involving nine clinical sites throughout the United States designed to assess the feasibility of ICM implants in a non-hospital setting. Other than the Reveal® ICM, implant supplies and techniques were left to physician discretion in patients who met indications. Patients were followed up to 90 days post-implant. The primary objective was to characterize the number of procedure-related adverse events that required surgical intervention within 90 days. RESULTS: Sixty-five patients were implanted at nine out-of-hospital sites. The insertion procedure was well tolerated by all patients. There were no deaths, systemic infections or endocarditis. There were two (3% procedure-related adverse events requiring device explant and four (6% adverse events not requiring explant. ICM use led to 16 diagnoses (24.6% with 9 patients proceeding to alternate cardiac device implants during the course of the 90-day follow up. CONCLUSION: Out-of-hospital ICM insertion can be accomplished with comparable procedural safety and represents a reasonable alternative to the in-hospital setting. CLINICALTRIALS.GOV REGISTRATION NUMBER: NCT01168427.

  14. Electrophysiological Data and the Biophysical Modelling of Local Cortical Circuits

    Directory of Open Access Journals (Sweden)

    Dimitris Pinotsis

    2014-03-01

    neuroscience, see e.g. [2] for a review. In summary, neural fields include horizontal intrinsic connections within layers or laminae of the cortical sheet and prescribe the time evolution of cell activity – such as mean depolarization or (average action potential density. These models characterize current fluxes as continuous processes on the cortical sheet, using partial differential equations (PDEs. The key advance that neural field models offer, over other population models (like neural masses, is that they embody spatial parameters (like the density and extent of lateral connections. This allows one to model responses not just in time but also over space. Conversely, these models are particularly useful for explaining observed cortical responses over different spatial scales; for example, with high-density recordings, at the epidural or intracortical level. However, the impact of spatially extensive dynamics is not restricted to expression over space but can also have profound effects on temporal (e.g., spectral responses at one point (or averaged locally over the cortical surface. This means that neural field models may also play a key role in the modelling of non-invasive electrophysiological data that does not resolve spatial activity directly. Our overview comprises two parts: in the first part, we use neural fields to simulate neural activity and distinguish the effects of post synaptic filtering on predicted responses in terms of synaptic rate constants that correspond to different timescales and distinct neurotransmitters. This application of neural fields follows the tradition of many studies, in which neural fields (and mean field models in general have been used to explain cortical activity based on qualitative changes of models activity induced by changes in model parameters, like synaptic efficacy and connection strengths, see e.g.[3–8] . We will focus on the links between neuronal oscillations – mediated by the lateral propagation of neuronal spiking

  15. Ranolazine: Electrophysiologic Effect, Efficacy, and Safety in Patients with Cardiac Arrhythmias.

    Science.gov (United States)

    Shenasa, Mohammad; Assadi, Hamid; Heidary, Shahriar; Shenasa, Hossein

    2016-06-01

    Ranolazine is currently approved as an antianginal agent in patients with chronic angina (class IIA). Ranolazine exhibits antiarrhythmic effects that are related to its multichannel blocking effect, predominantly inhibition of late sodium (late INa) current and the rapid potassium rectifier current (IKr), as well as ICa, late ICa, and INa-Ca. It also suppresses the early and delayed after depolarizations. Ranolazine is effective in the suppression of atrial and ventricular arrhythmias (off-label use) without significant proarrhythmic effect. Currently, ongoing trials are evaluating the efficacy and safety of ranolazine in patients with cardiac arrhythmias; preliminary results suggest that ranolazine, when used alone or in combination with dronedarone, is safe and effective in reducing atrial fibrillation. Ranolazine is not currently approved by the US Food and Drug Administration as an antiarrhythmic agent.

  16. Modeling Electrophysiological Coupling and Fusion between Human Mesenchymal Stem Cells and Cardiomyocytes.

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    Joshua Mayourian

    2016-07-01

    Full Text Available Human mesenchymal stem cell (hMSC delivery has demonstrated promise in preclinical and clinical trials for myocardial infarction therapy; however, broad acceptance is hindered by limited understanding of hMSC-human cardiomyocyte (hCM interactions. To better understand the electrophysiological consequences of direct heterocellular connections between hMSCs and hCMs, three original mathematical models were developed, representing an experimentally verified triad of hMSC families with distinct functional ion channel currents. The arrhythmogenic risk of such direct electrical interactions in the setting of healthy adult myocardium was predicted by coupling and fusing these hMSC models to the published ten Tusscher midcardial hCM model. Substantial variations in action potential waveform-such as decreased action potential duration (APD and plateau height-were found when hCMs were coupled to the two hMSC models expressing functional delayed rectifier-like human ether à-go-go K+ channel 1 (hEAG1; the effects were exacerbated for fused hMSC-hCM hybrid cells. The third family of hMSCs (Type C, absent of hEAG1 activity, led to smaller single-cell action potential alterations during coupling and fusion, translating to longer tissue-level mean action potential wavelength. In a simulated 2-D monolayer of cardiac tissue, re-entry vulnerability with low (5% hMSC insertion was approximately eight-fold lower with Type C hMSCs compared to hEAG1-functional hMSCs. A 20% decrease in APD dispersion by Type C hMSCs compared to hEAG1-active hMSCs supports the claim of reduced arrhythmogenic potential of this cell type with low hMSC insertion. However, at moderate (15% and high (25% hMSC insertion, the vulnerable window increased independent of hMSC type. In summary, this study provides novel electrophysiological models of hMSCs, predicts possible arrhythmogenic effects of hMSCs when directly coupled to healthy hCMs, and proposes that isolating a subset of hMSCs absent

  17. Predictive Modeling of Cardiac Ischemia

    Science.gov (United States)

    Anderson, Gary T.

    1996-01-01

    The goal of the Contextual Alarms Management System (CALMS) project is to develop sophisticated models to predict the onset of clinical cardiac ischemia before it occurs. The system will continuously monitor cardiac patients and set off an alarm when they appear about to suffer an ischemic episode. The models take as inputs information from patient history and combine it with continuously updated information extracted from blood pressure, oxygen saturation and ECG lines. Expert system, statistical, neural network and rough set methodologies are then used to forecast the onset of clinical ischemia before it transpires, thus allowing early intervention aimed at preventing morbid complications from occurring. The models will differ from previous attempts by including combinations of continuous and discrete inputs. A commercial medical instrumentation and software company has invested funds in the project with a goal of commercialization of the technology. The end product will be a system that analyzes physiologic parameters and produces an alarm when myocardial ischemia is present. If proven feasible, a CALMS-based system will be added to existing heart monitoring hardware.

  18. A guide to modelling cardiac electrical activity in anatomically detailed ventricles.

    Science.gov (United States)

    Clayton, R H; Panfilov, A V

    2008-01-01

    One of the most recent trends in cardiac electrophysiology is the development of integrative anatomically accurate models of the heart, which include description of cardiac activity from sub-cellular and cellular level to the level of the whole organ. In order to construct this type of model, a researcher needs to collect a wide range of information from books and journal articles on various aspects of biology, physiology, electrophysiology, numerical mathematics and computer programming. The aim of this methodological article is to survey recent developments in integrative modelling of electrical activity in the ventricles of the heart, and to provide a practical guide to the resources and tools that are available for work in this exciting and challenging area.

  19. Cardiac disease and arrhythmogenesis: Mechanistic insights from mouse models

    Directory of Open Access Journals (Sweden)

    Lois Choy

    2016-09-01

    Full Text Available The mouse is the second mammalian species, after the human, in which substantial amount of the genomic information has been analyzed. With advances in transgenic technology, mutagenesis is now much easier to carry out in mice. Consequently, an increasing number of transgenic mouse systems have been generated for the study of cardiac arrhythmias in ion channelopathies and cardiomyopathies. Mouse hearts are also amenable to physical manipulation such as coronary artery ligation and transverse aortic constriction to induce heart failure, radiofrequency ablation of the AV node to model complete AV block and even implantation of a miniature pacemaker to induce cardiac dyssynchrony. Last but not least, pharmacological models, despite being simplistic, have enabled us to understand the physiological mechanisms of arrhythmias and evaluate the anti-arrhythmic properties of experimental agents, such as gap junction modulators, that may be exert therapeutic effects in other cardiac diseases. In this article, we examine these in turn, demonstrating that primary inherited arrhythmic syndromes are now recognized to be more complex than abnormality in a particular ion channel, involving alterations in gene expression and structural remodelling. Conversely, in cardiomyopathies and heart failure, mutations in ion channels and proteins have been identified as underlying causes, and electrophysiological remodelling are recognized pathological features. Transgenic techniques causing mutagenesis in mice are extremely powerful in dissecting the relative contributions of different genes play in producing disease phenotypes. Mouse models can serve as useful systems in which to explore how protein defects contribute to arrhythmias and direct future therapy.

  20. A New Model to Perform Electrophysiological Studies in the Early Embryonic Mouse Heart

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    Anna Kornblum

    2013-07-01

    Full Text Available Background: The first electrocardiograms (ECGs have been recorded with a capillary electrometer in the late 19th century by John Burdon Sanderson and Augustus Waller. In 1903 Willem Einthoven used the much more sensitive string galvanometer and was awarded Nobel Price in Medicine for this discovery. Though the physical principles of that era are still in use, there have been many advances but also challenges in cardiac electrophysiology over the last decades. One challenge is to record electrocardiograms of rather small animals such as mice and even smaller organisms such as their embryos. As mice belong to the most routinely used laboratory animals it is important to better understand their physiology and specific diseases. We therefore aimed to study whether it is feasible to measure electrical activities of embryonic mouse hearts. Methods and Results: For our studies we used substrate-integrated Microelectrode Arrays combined with newly developed stimulation electrodes to perform electrophysiological studies in these hearts. The system enabled us to perform ECG-like recordings with atrio-ventricular (anterograde and ventriculo-atrial (retrograde stimulation. The functional separation of atria and ventricles, indicated by a stable atrio-ventricular conduction time, occurred clearly earlier than the morphological separation. Electrical stimulation induced a reversible prolongation of the anterograde and retrograde conduction up to atrio-ventricular conduction blocks at higher frequencies. Conclusion: These results yield new insight into functional aspects of murine cardiac development, and may help as a new diagnostic tool to uncover the functional and electrophysiological background of embryonic cardiac phenotypes of genetically altered mice.

  1. An inverse problem for a semilinear parabolic equation arising from cardiac electrophysiology

    Science.gov (United States)

    Beretta, Elena; Cavaterra, Cecilia; Cerutti, M. Cristina; Manzoni, Andrea; Ratti, Luca

    2017-10-01

    In this paper we develop theoretical analysis and numerical reconstruction techniques for the solution of an inverse boundary value problem dealing with the nonlinear, time-dependent monodomain equation, which models the evolution of the electric potential in the myocardial tissue. The goal is the detection of an inhomogeneity \

  2. Conditional shape models for cardiac motion estimation

    DEFF Research Database (Denmark)

    Metz, Coert; Baka, Nora; Kirisli, Hortense

    2010-01-01

    We propose a conditional statistical shape model to predict patient specific cardiac motion from the 3D end-diastolic CTA scan. The model is built from 4D CTA sequences by combining atlas based segmentation and 4D registration. Cardiac motion estimation is, for example, relevant in the dynamic...

  3. Mathematical modeling of heterogeneous electrophysiological responses in human β-cells.

    Directory of Open Access Journals (Sweden)

    Michela Riz

    2014-01-01

    Full Text Available Electrical activity plays a pivotal role in glucose-stimulated insulin secretion from pancreatic β-cells. Recent findings have shown that the electrophysiological characteristics of human β-cells differ from their rodent counterparts. We show that the electrophysiological responses in human β-cells to a range of ion channels antagonists are heterogeneous. In some cells, inhibition of small-conductance potassium currents has no effect on action potential firing, while it increases the firing frequency dramatically in other cells. Sodium channel block can sometimes reduce action potential amplitude, sometimes abolish electrical activity, and in some cells even change spiking electrical activity to rapid bursting. We show that, in contrast to L-type Ca2+-channels, P/Q-type Ca2+-currents are not necessary for action potential generation, and, surprisingly, a P/Q-type Ca2+-channel antagonist even accelerates action potential firing. By including SK-channels and Ca2+ dynamics in a previous mathematical model of electrical activity in human β-cells, we investigate the heterogeneous and nonintuitive electrophysiological responses to ion channel antagonists, and use our findings to obtain insight in previously published insulin secretion measurements. Using our model we also study paracrine signals, and simulate slow oscillations by adding a glycolytic oscillatory component to the electrophysiological model. The heterogenous electrophysiological responses in human β-cells must be taken into account for a deeper understanding of the mechanisms underlying insulin secretion in health and disease, and as shown here, the interdisciplinary combination of experiments and modeling increases our understanding of human β-cell physiology.

  4. Effect and mechanism of fluoxetine on electrophysiology in vivo in a rat model of postmyocardial infarction depression

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    Liang J

    2015-02-01

    Full Text Available Jinjun Liang,1,2 Xiaoran Yuan,1,2 Shaobo Shi,1,2 Fang Wang,1,2 Yingying Chen,1,2 Chuan Qu,1,2 Jingjing Chen,1,2 Dan Hu,1–3 Yang Bo1,2 1Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 2Cardiovascular Research Institute, Wuhan University, Wuhan, People’s Republic of China; 3Masonic Medical Research Laboratory, Utica, NY, USA Background: Major depression is diagnosed in 18% of patients following myocardial infarction (MI, and the antidepressant fluoxetine is shown to effectively decrease depressive symptoms and improve coronary heart disease prognosis. We observed the effect of fluoxetine on cardiac electrophysiology in vivo in a rat model of post-MI depression and the potential mechanism. Methods and results: Eighty adult male Sprague Dawley rats (200–250 g were randomly assigned to five groups: normal control (control group, MI (MI group, depression (depression group, post-MI depression (model group, and post-MI depression treated with intragastric administration of 10 mg/kg fluoxetine (fluoxetine group. MI was induced by left anterior descending coronary artery ligation. Depression was developed by 4-week chronic mild stress (CMS. Behavior measurement was done before and during the experiment. Electrophysiology study in vivo and Western blot analysis were carried on after 4 weeks of CMS. After 4 weeks of CMS, depression-like behaviors were observed in the MI, depression, and model groups, and chronic fluoxetine administration could significantly improve those behaviors (P<0.05 vs model group. Fluoxetine significantly increased the ventricular fibrillation threshold compared with the model group (20.20±9.32 V vs 14.67±1.85 V, P<0.05. Expression of Kv4.2 was significantly reduced by 29%±12%, 24%±6%, and 41%±15%, respectively, in the MI group, CMS group, and model group, which could be improved by fluoxetine (30%±9%. But fluoxetine showed no improvement on the MI-induced loss of Cx43

  5. Slow [Na+]i dynamics impacts arrhythmogenesis and spiral wave reentry in cardiac myocyte ionic model

    Science.gov (United States)

    Krogh-Madsen, Trine; Christini, David J.

    2017-09-01

    Accumulation of intracellular Na+ is gaining recognition as an important regulator of cardiac myocyte electrophysiology. The intracellular Na+ concentration can be an important determinant of the cardiac action potential duration, can modulate the tissue-level conduction of excitation waves, and can alter vulnerability to arrhythmias. Mathematical models of cardiac electrophysiology often incorporate a dynamic intracellular Na+ concentration, which changes much more slowly than the remaining variables. We investigated the dependence of several arrhythmogenesis-related factors on [Na+]i in a mathematical model of the human atrial action potential. In cell simulations, we found that [Na+]i accumulation stabilizes the action potential duration to variations in several conductances and that the slow dynamics of [Na+]i impacts bifurcations to pro-arrhythmic afterdepolarizations, causing intermittency between different rhythms. In long-lasting tissue simulations of spiral wave reentry, [Na+]i becomes spatially heterogeneous with a decreased area around the spiral wave rotation center. This heterogeneous region forms a functional anchor, resulting in diminished meandering of the spiral wave. Our findings suggest that slow, physiological, rate-dependent variations in [Na+]i may play complex roles in cellular and tissue-level cardiac dynamics.

  6. Non-conforming finite-element formulation for cardiac electrophysiology: an effective approach to reduce the computation time of heart simulations without compromising accuracy

    Science.gov (United States)

    Hurtado, Daniel E.; Rojas, Guillermo

    2017-08-01

    Computer simulations constitute a powerful tool for studying the electrical activity of the human heart, but computational effort remains prohibitively high. In order to recover accurate conduction velocities and wavefront shapes, the mesh size in linear element (Q1) formulations cannot exceed 0.1 mm. Here we propose a novel non-conforming finite-element formulation for the non-linear cardiac electrophysiology problem that results in accurate wavefront shapes and lower mesh-dependance in the conduction velocity, while retaining the same number of global degrees of freedom as Q1 formulations. As a result, coarser discretizations of cardiac domains can be employed in simulations without significant loss of accuracy, thus reducing the overall computational effort. We demonstrate the applicability of our formulation in biventricular simulations using a coarse mesh size of ˜ 1 mm, and show that the activation wave pattern closely follows that obtained in fine-mesh simulations at a fraction of the computation time, thus improving the accuracy-efficiency trade-off of cardiac simulations.

  7. Statistics on the use of cardiac electronic devices and electrophysiological procedures in the European Society of Cardiology countries: 2014 report from the European Heart Rhythm Association.

    Science.gov (United States)

    Raatikainen, M J Pekka; Arnar, David O; Zeppenfeld, Katja; Merino, Jose Luis; Levya, Francisco; Hindriks, Gerhardt; Kuck, Karl-Heinz

    2015-01-01

    There has been large variations in the use of invasive electrophysiological therapies in the member countries of the European Society of Cardiology (ESC). The aim of this analysis was to provide comprehensive information on cardiac implantable electronic device (CIED) and catheter ablation therapy trends in the ESC countries over the last five years. The European Heart Rhythm Association (EHRA) has collected data on CIED and catheter ablation therapy since 2008. Last year 49 of the 56 ESC member countries provided data for the EHRA White Book. This analysis is based on the current and previous editions of the EHRA White Book. Data on procedure rates together with information on economic aspects, local reimbursement systems and training activities are presented for each ESC country and the five geographical ESC regions. In 2013, the electrophysiological procedure rates per million population were highest in Western Europe followed by the Southern and Northern European countries. The CIED implantation and catheter ablation rate was lowest in the Eastern European and in the non-European ESC countries, respectively. However, in some Eastern European countries with relative low gross domestic product procedure rates exceeded those of some wealthier Western countries, suggesting that economic resources are not the only driver for utilization of arrhythmia therapies. These statistics indicate that despite significant improvements, there still is considerable heterogeneity in the availability of arrhythmia therapies across the ESC area. Hopefully, these data will help identify areas for improvement and guide future activities in cardiac arrhythmia management. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

  8. Electrophysiological analysis of neuromuscular synaptic function in myasthenia gravis patients and animal models.

    Science.gov (United States)

    Plomp, Jaap J; Morsch, Marco; Phillips, William D; Verschuuren, Jan J G M

    2015-08-01

    Study of the electrophysiological function of the neuromuscular junction (NMJ) is instrumental in the understanding of the symptoms and pathophysiology of myasthenia gravis (MG), an autoimmune disorder characterized by fluctuating and fatigable muscle weakness. Most patients have autoantibodies to the acetylcholine receptor at the NMJ. However, in recent years autoantibodies to other crucial postsynaptic membrane proteins have been found in previously 'seronegative' MG patients. Electromyographical recording of compound and single-fibre muscle action potentials provides a crucial in vivo method to determine neuromuscular transmission failure while ex vivo (miniature) endplate potential recordings can reveal the precise synaptic impairment. Here we will review these electrophysiological methods used to assess NMJ function and discuss their application and typical results found in the diagnostic and experimental study of patients and animal models of the several forms of MG. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. The virtual intestine: in silico modeling of small intestinal electrophysiology and motility and the applications.

    Science.gov (United States)

    Du, Peng; Paskaranandavadivel, Niranchan; Angeli, Timothy R; Cheng, Leo K; O'Grady, Gregory

    2016-01-01

    The intestine comprises a long hollow muscular tube organized in anatomically and functionally discrete compartments, which digest and absorb nutrients and water from ingested food. The intestine also plays key roles in the elimination of waste and protection from infection. Critical to all of these functions is the intricate, highly coordinated motion of the intestinal tract, known as motility, which is coregulated by hormonal, neural, electrophysiological and other factors. The Virtual Intestine encapsulates a series of mathematical models of intestinal function in health and disease, with a current focus on motility, and particularly electrophysiology. The Virtual Intestine is being cohesively established across multiple physiological scales, from sub/cellular functions to whole organ levels, facilitating quantitative evaluations that present an integrative in silico framework. The models are also now finding broad physiological applications, including in evaluating hypotheses of slow wave pacemaker mechanisms, smooth muscle electrophysiology, structure-function relationships, and electromechanical coupling. Clinical applications are also beginning to follow, including in the pathophysiology of motility disorders, diagnosing intestinal ischemia, and visualizing colonic dysfunction. These advances illustrate the emerging potential of the Virtual Intestine to effectively address multiscale research challenges in interdisciplinary gastrointestinal sciences.

  10. Genetic Mouse Models of Huntington's Disease: Focus on Electrophysiological Mechanisms

    Directory of Open Access Journals (Sweden)

    Carlos Cepeda

    2010-03-01

    Full Text Available The discovery of the HD (Huntington's disease gene in 1993 led to the creation of genetic mouse models of the disease and opened the doors for mechanistic studies. In particular, the early changes and progression of the disease could be followed and examined systematically. The present review focuses on the contribution of these genetic mouse models to the understanding of functional changes in neurons as the HD phenotype progresses, and concentrates on two brain areas: the striatum, the site of most conspicuous pathology in HD, and the cortex, a site that is becoming increasingly important in understanding the widespread behavioural abnormalities. Mounting evidence points to synaptic abnormalities in communication between the cortex and striatum and cell-cell interactions as major determinants of HD symptoms, even in the absence of severe neuronal degeneration and death.

  11. Electrophysiological correlates of listening effort: neurodynamical modeling and measurement.

    Science.gov (United States)

    Strauss, Daniel J; Corona-Strauss, Farah I; Trenado, Carlos; Bernarding, Corinna; Reith, Wolfgang; Latzel, Matthias; Froehlich, Matthias

    2010-06-01

    An increased listing effort represents a major problem in humans with hearing impairment. Neurodiagnostic methods for an objective listening effort estimation might support hearing instrument fitting procedures. However the cognitive neurodynamics of listening effort is far from being understood and its neural correlates have not been identified yet. In this paper we analyze the cognitive neurodynamics of listening effort by using methods of forward neurophysical modeling and time-scale electroencephalographic neurodiagnostics. In particular, we present a forward neurophysical model for auditory late responses (ALRs) as large-scale listening effort correlates. Here endogenously driven top-down projections related to listening effort are mapped to corticothalamic feedback pathways which were analyzed for the selective attention neurodynamics before. We show that this model represents well the time-scale phase stability analysis of experimental electroencephalographic data from auditory discrimination paradigms. It is concluded that the proposed neurophysical and neuropsychological framework is appropriate for the analysis of listening effort and might help to develop objective electroencephalographic methods for its estimation in future.

  12. Structural and electrical myocardial remodeling in a rodent model of depression

    NARCIS (Netherlands)

    Carnevali, Luca; Trombini, Mimosa; Rossi, Stefano; Graiani, Gallia; Manghi, Massimo; Koolhaas, Jaap M.; Quaini, Federico; Macchi, Emilio; Nalivaiko, Eugene; Sgoifo, Andrea

    2013-01-01

    Objective: Despite a well-documented association between stress and depression with cardiac morbidity and mortality, there is no satisfactory explanation for the mechanisms linking affective and cardiac disorders. This study investigated cardiac electrophysiological properties in an animal model of

  13. Toward the virtual stomach: progress in multiscale modeling of gastric electrophysiology and motility.

    Science.gov (United States)

    Du, Peng; O'Grady, Gregory; Gao, Jerry; Sathar, Shameer; Cheng, Leo K

    2013-01-01

    Experimental progress in investigating normal and disordered gastric motility is increasingly being complimented by sophisticated multiscale modeling studies. Mathematical modeling has become a valuable tool in this effort, as there is an ever-increasing need to gain an integrative and quantitative understanding of how physiological mechanisms achieve coordinated functions across multiple biophysical scales. These interdisciplinary efforts have been particularly notable in the area of gastric electrophysiology, where they are beginning to yield a comprehensive and integrated in silico organ modeling framework, or 'virtual stomach'. At the cellular level, a number of biophysically based mathematical cell models have been developed, and these are now being applied in areas including investigations of gastric electrical pacemaker mechanisms, smooth muscle electrophysiology, and electromechanical coupling. At the tissue level, micro-structural models are being creatively developed and employed to investigate clinically significant questions, such as the functional effects of ICC degradation on gastrointestinal (GI) electrical activation. At the organ level, high-resolution electrical mapping and modeling studies are combined to provide improved insights into normal and dysrhythmic gastric electrical activation. These efforts are also enabling detailed forward and inverse modeling studies at the 'whole body' level, with implications for diagnostic techniques for gastric dysrhythmias. These recent advances, together with several others highlighted in this review, collectively demonstrate a powerful trend toward applying mathematical models to effectively investigate structure-function relationships and overcome multiscale challenges in basic and clinical GI research.

  14. Excitation model of pacemaker cardiomyocytes of cardiac conduction system

    Science.gov (United States)

    Grigoriev, M.; Babich, L.

    2015-11-01

    Myocardium includes typical and atypical cardiomyocytes - pacemakers, which form the cardiac conduction system. Excitation from the atrioventricular node in normal conditions is possible only in one direction. Retrograde direction of pulses is impossible. The most important prerequisite for the work of cardiomyocytes is the anatomical integrity of the conduction system. Changes in contractile force of the cardiomyocytes, which appear periodically, are due to two mechanisms of self-regulation - heterometric and homeometric. Graphic course of the excitation pulse propagation along the heart muscle more accurately reveals the understanding of the arrhythmia mechanism. These models have the ability to visualize the essence of excitation dynamics. However, they do not have the proper forecasting function for result estimation. Integrative mathematical model enables further investigation of general laws of the myocardium active behavior, allows for determination of the violation mechanism of electrical and contractile function of cardiomyocytes. Currently, there is no full understanding of the topography of pacemakers and ionic mechanisms. There is a need for the development of direction of mathematical modeling and comparative studies of the electrophysiological arrangement of cells of atrioventricular connection and ventricular conduction system.

  15. Neo: an object model for handling electrophysiology data in multiple formats

    Directory of Open Access Journals (Sweden)

    Samuel eGarcia

    2014-02-01

    Full Text Available Neuroscientists use many different software tools to acquire, analyse and visualise electrophysiological signals. However, incompatible data models and file formats make it difficult to exchange data between these tools. This reduces scientific productivity, renders potentially useful analysis methods inaccessible and impedes collaboration between labs.A common representation of the core data would improve interoperability and facilitate data-sharing.To that end, we propose here a language-independent object model, named Neo, suitable for representing data acquired from electroencephalographic, intracellular, or extracellular recordings, or generated from simulations. As a concrete instantiation of this object model we have developed an open source implementation in the Python programming language.In addition to representing electrophysiology data in memory for the purposes of analysis and visualisation, the Python implementation provides a set of input/output (IO modules for reading/writing the data from/to a variety of commonly used file formats.Support is included for formats produced by most of the major manufacturers of electrophysiology recording equipment and also for more generic formats such as MATLAB.Data representation and data analysis are conceptually separate: it is easier to write robust analysis code if it is focused on analysis and relies on an underlying package to handle data representation.For that reason, and also to be as lightweight as possible, the Neo object model and the associated Python package are deliberately limited to representation of data, with no functions for data analysis or visualisation.Software for neurophysiology data analysis and visualisation built on top of Neo automatically gains the benefits of interoperability, easier data sharing and automatic format conversion; there is already a burgeoning ecosystem of such tools. We intend that Neo should become the standard basis for Python tools in

  16. Neo: an object model for handling electrophysiology data in multiple formats.

    Science.gov (United States)

    Garcia, Samuel; Guarino, Domenico; Jaillet, Florent; Jennings, Todd; Pröpper, Robert; Rautenberg, Philipp L; Rodgers, Chris C; Sobolev, Andrey; Wachtler, Thomas; Yger, Pierre; Davison, Andrew P

    2014-01-01

    Neuroscientists use many different software tools to acquire, analyze and visualize electrophysiological signals. However, incompatible data models and file formats make it difficult to exchange data between these tools. This reduces scientific productivity, renders potentially useful analysis methods inaccessible and impedes collaboration between labs. A common representation of the core data would improve interoperability and facilitate data-sharing. To that end, we propose here a language-independent object model, named "Neo," suitable for representing data acquired from electroencephalographic, intracellular, or extracellular recordings, or generated from simulations. As a concrete instantiation of this object model we have developed an open source implementation in the Python programming language. In addition to representing electrophysiology data in memory for the purposes of analysis and visualization, the Python implementation provides a set of input/output (IO) modules for reading/writing the data from/to a variety of commonly used file formats. Support is included for formats produced by most of the major manufacturers of electrophysiology recording equipment and also for more generic formats such as MATLAB. Data representation and data analysis are conceptually separate: it is easier to write robust analysis code if it is focused on analysis and relies on an underlying package to handle data representation. For that reason, and also to be as lightweight as possible, the Neo object model and the associated Python package are deliberately limited to representation of data, with no functions for data analysis or visualization. Software for neurophysiology data analysis and visualization built on top of Neo automatically gains the benefits of interoperability, easier data sharing and automatic format conversion; there is already a burgeoning ecosystem of such tools. We intend that Neo should become the standard basis for Python tools in neurophysiology.

  17. Automatic Construction of Predictive Neuron Models through Large Scale Assimilation of Electrophysiological Data

    Science.gov (United States)

    Nogaret, Alain; Meliza, C. Daniel; Margoliash, Daniel; Abarbanel, Henry D. I.

    2016-09-01

    We report on the construction of neuron models by assimilating electrophysiological data with large-scale constrained nonlinear optimization. The method implements interior point line parameter search to determine parameters from the responses to intracellular current injections of zebra finch HVC neurons. We incorporated these parameters into a nine ionic channel conductance model to obtain completed models which we then use to predict the state of the neuron under arbitrary current stimulation. Each model was validated by successfully predicting the dynamics of the membrane potential induced by 20–50 different current protocols. The dispersion of parameters extracted from different assimilation windows was studied. Differences in constraints from current protocols, stochastic variability in neuron output, and noise behave as a residual temperature which broadens the global minimum of the objective function to an ellipsoid domain whose principal axes follow an exponentially decaying distribution. The maximum likelihood expectation of extracted parameters was found to provide an excellent approximation of the global minimum and yields highly consistent kinetics for both neurons studied. Large scale assimilation absorbs the intrinsic variability of electrophysiological data over wide assimilation windows. It builds models in an automatic manner treating all data as equal quantities and requiring minimal additional insight.

  18. Fitting of adaptive neuron model to electrophysiological recordings using particle swarm optimization algorithm

    Science.gov (United States)

    Shan, Bonan; Wang, Jiang; Zhang, Lvxia; Deng, Bin; Wei, Xile

    2017-02-01

    In order to fit neural model’s spiking features to electrophysiological recordings, in this paper, a fitting framework based on particle swarm optimization (PSO) algorithm is proposed to estimate the model parameters in an augmented multi-timescale adaptive threshold (AugMAT) model. PSO algorithm is an advanced evolutionary calculation method based on iteration. Selecting a reasonable criterion function will ensure the effectiveness of PSO algorithm. In this work, firing rate information is used as the main spiking feature and the estimation error of firing rate is selected as the criterion for fitting. A series of simulations are presented to verify the performance of the framework. The first step is model validation; an artificial training data is introduced to test the fitting procedure. Then we talk about the suitable PSO parameters, which exhibit adequate compromise between speediness and accuracy. Lastly, this framework is used to fit the electrophysiological recordings, after three adjustment steps, the features of experimental data are translated into realistic spiking neuron model.

  19. State and parameter estimation of a neural mass model from electrophysiological signals during the status epilepticus.

    Science.gov (United States)

    López-Cuevas, Armando; Castillo-Toledo, Bernardino; Medina-Ceja, Laura; Ventura-Mejía, Consuelo

    2015-06-01

    Status epilepticus is an emergency condition in patients with prolonged seizure or recurrent seizures without full recovery between them. The pathophysiological mechanisms of status epilepticus are not well established. With this argument, we use a computational modeling approach combined with in vivo electrophysiological data obtained from an experimental model of status epilepticus to infer about changes that may lead to a seizure. Special emphasis is done to analyze parameter changes during or after pilocarpine administration. A cubature Kalman filter is utilized to estimate parameters and states of the model in real time from the observed electrophysiological signals. It was observed that during basal activity (before pilocarpine administration) the parameters presented a standard deviation below 30% of the mean value, while during SE activity, the parameters presented variations larger than 200% of the mean value with respect to basal state. The ratio of excitation-inhibition, increased during SE activity by 80% with respect to the transition state, and reaches the lowest value during cessation. In addition, a progression between low and fast inhibitions before or during this condition was found. This method can be implemented in real time, which is particularly important for the design of stimulation devices that attempt to stop seizures. These changes in the parameters analyzed during seizure activity can lead to better understanding of the mechanisms of epilepsy and to improve its treatments.

  20. Finite Element Model of Cardiac Electrical Conduction.

    Science.gov (United States)

    Yin, John Zhihao

    1994-01-01

    In this thesis, we develop mathematical models to study electrical conduction of the heart. One important pattern of wave propagation of electrical excitation in the heart is reentry which is believed to be the underlying mechanism of some dangerous cardiac arhythmias such as ventricular tachycardia and ventricular fibrillation. We present in this thesis a new ionic channel model of the ventricular cardiac cell membrane to study the microscopic electrical properties of myocardium. We base our model on recent single channel experiment data and a simple physical diffusion model of the calcium channel. Our ionic channel model of myocardium has simpler differential equations and fewer parameters than previous models. Further more, our ionic channel model achieves better results in simulating the strength-interval curve when we connect the membrane patch model to form a one dimensional cardiac muscle strand. We go on to study a finite element model which uses multiple states and non-nearest neighbor interactions to include curvature and dispersion effects. We create a generalized lattice randomization to overcome the artifacts generated by the interaction between the local dynamics and the regularities of the square lattice. We show that the homogeneous model does not display spontaneous wavefront breakup in a reentrant wave propagation once the lattice artifacts have been smoothed out by lattice randomization with a randomization scale larger than the characteristic length of the interaction. We further develop a finite 3-D 3-state heart model which employs a probability interaction rule. This model is applied to the simulation of Body Surface Laplacian Mapping (BSLM) using a cylindrical volume conductor as the torso model. We show that BSLM has a higher spatial resolution than conventional mapping methods in revealing the underlying electrical activities of the heart. The results of these studies demonstrate that mathematical modeling and computer simulation are very

  1. Charting a course for cardiac electrophysiology training in Canada: the vital role of fellows in advanced cardiovascular care.

    Science.gov (United States)

    Leather, Richard A; Gardner, Martin; Green, Martin S; Kavanagh, Katherine; Macle, Laurent; Ahmad, Kamran; Gray, Chris; Ayala-Paredes, Felix; Guerra, Peter G; O'Hara, Gilles; Essebag, Vidal; Sturmer, Marcio; Baranchuk, Adrian; Hruczkowski, Tomasz; Lahevsky, Ilan; Novak, Paul; Chakrabarti, Shanta; Harris, Louise; Gula, Lorne J; Morillo, Carlos; Sanatani, Shubhayan; Hamilton, Robert M; Gow, Robert M; Krahn, Andrew D

    2013-11-01

    Canadian electrophysiology (EP) fellowship programs have evolved in an ad hoc fashion over 30 years. This evolution has occurred in many fields in medicine and is natural when innovators and pioneers attract research fellows who help change the status quo from predominantly research to a predominantly clinical application and focus. Fellows not only push their supervisors and their centres into new areas of inquiry but also function at the most advanced level to encourage and teach junior trainees and to provide examples of excellence to residents, medical students, and other health professionals. Funding for fellows has never been provided in the traditional way through the Ministry of Health or the Ministry of Advanced Education. Each Canadian centre has over the years found novel ways to fund fellowship programs, and many centres have used value-adds from procurement programs. These sources of funding are eroding as provincial government agencies are beginning to assume procurement responsibilities and local flexibility to fund fellowships is lost. In particular, provincial government agencies feel that valuable financial resources should be restricted to Canadian trainees only, despite the international consensus that fellowship is an essential time for advanced trainees to travel abroad to acquire a broad a range of experience, learn new techniques and approaches, make lifelong research connections, and hopefully return home with these skills and expertise. This article summarizes the long history of EP fellowship training in Canada, as well as EP fellowship experiences at home and abroad by Canadian electrophysiologists, in an attempt to contextualize these new realities.

  2. Somato-dendritic mechanisms underlying the electrophysiological properties of hypothalamic magnocellular neuroendocrine cells: a multicompartmental model study.

    Science.gov (United States)

    Komendantov, Alexander O; Trayanova, Natalia A; Tasker, Jeffrey G

    2007-10-01

    Magnocellular neuroendocrine cells (MNCs) of the hypothalamus synthesize the neurohormones vasopressin and oxytocin, which are released into the blood and exert a wide spectrum of actions, including the regulation of cardiovascular and reproductive functions. Vasopressin- and oxytocin-secreting neurons have similar morphological structure and electrophysiological characteristics. A realistic multicompartmental model of a MNC with a bipolar branching structure was developed and calibrated based on morphological and in vitro electrophysiological data in order to explore the roles of ion currents and intracellular calcium dynamics in the intrinsic electrical MNC properties. The model was used to determine the likely distributions of ion conductances in morphologically distinct parts of the MNCs: soma, primary dendrites and secondary dendrites. While reproducing the general electrophysiological features of MNCs, the model demonstrates that the differential spatial distributions of ion channels influence the functional expression of MNC properties, and reveals the potential importance of dendritic conductances in these properties.

  3. Modeling bipolar stimulation of cardiac tissue

    Science.gov (United States)

    Galappaththige, Suran K.; Gray, Richard A.; Roth, Bradley J.

    2017-09-01

    Unipolar stimulation of cardiac tissue is often used in the design of cardiac pacemakers because of the low current required to depolarize the surrounding tissue at rest. However, the advantages of unipolar over bipolar stimulation are not obvious at shorter coupling intervals when the tissue near the pacing electrode is relatively refractory. Therefore, this paper analyzes bipolar stimulation of cardiac tissue. The strength-interval relationship for bipolar stimulation is calculated using the bidomain model and a recently developed parsimonious ionic current model. The strength-interval curves obtained using different electrode separations and arrangements (electrodes placed parallel to the fibers versus perpendicular to the fibers) indicate that bipolar stimulation results in more complex activation patterns compared to unipolar stimulation. An unusually low threshold stimulus current is observed when the electrodes are close to each other (a separation of 1 mm) because of break excitation. Unlike for unipolar stimulation, anode make excitation is not present during bipolar stimulation, and an abrupt switch from anode break to cathode make excitation can cause dramatic changes in threshold with very small changes in the interval. These results could impact the design of implantable pacemakers and defibrillators.

  4. [Development of multi-channels cardiac electrophysiological polygraph with LabVIEW as software platform and its clinical application].

    Science.gov (United States)

    Fan, Shounian; Jiang, Yi; Jiang, Chenxi; Yang, Tianhe; Zhang, Chengyun; Liu, Junshi; Wu, Qiang; Zheng, Yaxi; Liu, Xiaoqiao

    2004-10-01

    Polygraph has become a necessary instrument in interventional cardiology and fundamental research of medicine up to the present. In this study, a LabView development system (DS) (developed by NI in U.S.) used as software platform, a DAQ data acquisition module and universal computer used as hardware platform, were creatively coupled with our self-made low noise multi-channels preamplifier to develop Multi-channels electrocardiograph. The device possessed the functions such as real time display of physiological process, digit highpass and lowpass, 50Hz filtered and gain adjustment, instant storing, random playback and printing, and process control stimulation. Besides, it was small-sized, economically practical and easy to operate. It could advance the spread of cardiac intervention treatment in hospitals.

  5. Induced pluripotent stem cell derived cardiomyocytes as models for cardiac arrhythmias

    Directory of Open Access Journals (Sweden)

    Maaike eHoekstra

    2012-08-01

    Full Text Available Cardiac arrhythmias are a major cause of morbidity and mortality. In younger patients, the majority of sudden cardiac deaths have an underlying Mendelian genetic cause. Over the last 15 years, enormous progress has been made in identifying the distinct clinical phenotypes and in studying the basic cellular and genetic mechanisms associated with the primary Mendelian (monogenic arrhythmia syndromes. Investigation of the electrophysiological consequences of an ion channel mutation is ideally done in the native cardiomyocyte environment. However, the majority of such studies so far have relied on heterologous expression systems in which single ion channel genes are expressed in non-cardiac cells. In some cases, transgenic mouse models haven been generated, but these also have significant shortcomings, primarily related to species differences.The discovery that somatic cells can be reprogrammed to pluripotency as induced pluripotent stem cells (iPSC has generated much interest since it presents an opportunity to generate patient- and disease-specific cell lines from which normal and diseased human cardiomyocytes can be obtained These genetically diverse human model systems can be studied in vitro and used to decipher mechanisms of disease and identify strategies and reagents for new therapies. Here we review the present state of the art with respect to cardiac disease models already generated using IPSC technology and which have been (partially characterized.Human iPSC (hiPSC models have been described for the cardiac arrhythmia syndromes, including LQT1, LQT2, LQT3-Brugada Syndrome, LQT8/Timothy syndrome and catecholaminergic polymorphic ventricular tachycardia. In most cases, the hiPSC-derived cardiomyoctes recapitulate the disease phenotype and have already provided opportunities for novel insight into cardiac pathophysiology. It is expected that the lines will be useful in the development of pharmacological agents for the management of these

  6. Induced pluripotent stem cell derived cardiomyocytes as models for cardiac arrhythmias.

    Science.gov (United States)

    Hoekstra, Maaike; Mummery, Christine L; Wilde, Arthur A M; Bezzina, Connie R; Verkerk, Arie O

    2012-01-01

    Cardiac arrhythmias are a major cause of morbidity and mortality. In younger patients, the majority of sudden cardiac deaths have an underlying Mendelian genetic cause. Over the last 15 years, enormous progress has been made in identifying the distinct clinical phenotypes and in studying the basic cellular and genetic mechanisms associated with the primary Mendelian (monogenic) arrhythmia syndromes. Investigation of the electrophysiological consequences of an ion channel mutation is ideally done in the native cardiomyocyte (CM) environment. However, the majority of such studies so far have relied on heterologous expression systems in which single ion channel genes are expressed in non-cardiac cells. In some cases, transgenic mouse models have been generated, but these also have significant shortcomings, primarily related to species differences. The discovery that somatic cells can be reprogrammed to pluripotency as induced pluripotent stem cells (iPSC) has generated much interest since it presents an opportunity to generate patient- and disease-specific cell lines from which normal and diseased human CMs can be obtained These genetically diverse human model systems can be studied in vitro and used to decipher mechanisms of disease and identify strategies and reagents for new therapies. Here, we review the present state of the art with respect to cardiac disease models already generated using IPSC technology and which have been (partially) characterized. Human iPSC (hiPSC) models have been described for the cardiac arrhythmia syndromes, including LQT1, LQT2, LQT3-Brugada Syndrome, LQT8/Timothy syndrome and catecholaminergic polymorphic ventricular tachycardia (CPVT). In most cases, the hiPSC-derived cardiomyoctes recapitulate the disease phenotype and have already provided opportunities for novel insight into cardiac pathophysiology. It is expected that the lines will be useful in the development of pharmacological agents for the management of these disorders.

  7. Computer Generated Cardiac Model For Nuclear Medicine

    Science.gov (United States)

    Hills, John F.; Miller, Tom R.

    1981-07-01

    A computer generated mathematical model of a thallium-201 myocardial image is described which is based on realistic geometric and physiological assumptions. The left ventricle is represented by an ellipsoid truncated by aortic and mitral valve planes. Initially, an image of a motionless left ventricle is calculated with the location, size, and relative activity of perfusion defects selected by the designer. The calculation includes corrections for photon attenuation by overlying structures and the relative distribution of activity within the tissues. Motion of the ventricular walls is simulated either by a weighted sum of images at different stages in the cardiac cycle or by a blurring function whose width varies with position. Camera and collimator blurring are estimated by the MTF of the system measured at a representative depth in a phantom. Statistical noise is added using a Poisson random number generator. The usefulness of this model is due to two factors: the a priori characterization of location and extent of perfusion defects and the strong visual similarity of the images to actual clinical studies. These properties should permit systematic evaluation of image processing algorithms using this model. The principles employed in developing this cardiac image model can readily be applied to the simulation of other nuclear medicine studies and to other medical imaging modalities including computed tomography, ultrasound, and digital radiography.

  8. Cardiac conduction system anomalies and sudden cardiac death: insights from murine models

    Directory of Open Access Journals (Sweden)

    Amelia Eva Aranega

    2012-06-01

    Full Text Available The cardiac conduction system (CCS is a series of specialized tissues in the heart responsible for the initiation and co-ordination of the heartbeat. Alterations in the CCS, especially the His-Purkinje system, have been identified as an important player in the generation of lethal arrhythmias. Unstable arrhythmias secondary to channelopathies highly increase the risk of sudden cardiac death (SCD. Sudden cardiac death is a major contributor to mortality in industrialized nations, and most cases of SCD in the young are related to inherited ion channel diseases. In this review we examine how murine transgenic models have contributed to understanding that a broad variety of cardiac arrhythmias involve the cardiac specialized conduction system and may lead to sudden cardiac death.

  9. Network dynamics of 3D engineered neuronal cultures: a new experimental model for in-vitro electrophysiology

    NARCIS (Netherlands)

    Frega, M.; Tedesco, M.; Massobrio, P.; Pesce, M.; Martinoia, S.

    2014-01-01

    Despite the extensive use of in-vitro models for neuroscientific investigations and notwithstanding the growing field of network electrophysiology, all studies on cultured cells devoted to elucidate neurophysiological mechanisms and computational properties, are based on 2D neuronal networks. These

  10. Reimplantation and Repeat Infection After Cardiac-Implantable Electronic Device Infections: Experience From the MEDIC (Multicenter Electrophysiologic Device Infection Cohort) Database.

    Science.gov (United States)

    Boyle, Thomas A; Uslan, Daniel Z; Prutkin, Jordan M; Greenspon, Arnold J; Baddour, Larry M; Danik, Stephan B; Tolosana, Jose M; Le, Katherine; Miro, Jose M; Peacock, James; Sohail, Muhammad R; Vikram, Holenarasipur R; Carrillo, Roger G

    2017-03-01

    Infection is a serious complication of cardiovascular-implantable electronic device implantation and necessitates removal of all hardware for optimal treatment. Strategies for reimplanting hardware after infection vary widely and have not previously been analyzed using a large, multicenter study. The MEDIC (Multicenter Electrophysiologic Device Infection Cohort) prospectively enrolled subjects with cardiovascular-implantable electronic device infections at multiple institutions in the United States and abroad between 2009 and 2012. Reimplantation strategies were evaluated overall, and every patient who relapsed within 6 months was individually examined for clinical information that could help explain the negative outcome. Overall, 434 patients with cardiovascular-implantable electronic device infections were prospectively enrolled at participating centers. During the initial course of therapy, complete device removal was done in 381 patients (87.8%), and 220 of them (57.7%) were ultimately reimplanted with new devices. Overall, the median time between removal and reimplantation was 10 days, with an interquartile range of 6 to 19 days. Eleven of the 434 patients had another infection within 6 months, but only 4 of them were managed with cardiovascular-implantable electronic device removal and reimplantation during the initial infection. Thus, the repeat infection rate was low (1.8%) in those who were reimplanted. Patients who retained original hardware had a 11.3% repeat infection rate. Our study findings confirm that a broad range of reimplant strategies are used in clinical practice. They suggest that it is safe to reimplant cardiac devices after extraction of previously infected hardware and that the risk of a second infection is low, regardless of reimplant timing. © 2017 American Heart Association, Inc.

  11. Differential Sarcomere and Electrophysiological Maturation of Human iPSC-Derived Cardiac Myocytes in Monolayer vs. Aggregation-Based Differentiation Protocols

    Directory of Open Access Journals (Sweden)

    Dorota Jeziorowska

    2017-06-01

    Full Text Available Human induced pluripotent stem cells (iPSCs represent a powerful human model to study cardiac disease in vitro, notably channelopathies and sarcomeric cardiomyopathies. Different protocols for cardiac differentiation of iPSCs have been proposed either based on embroid body formation (3D or, more recently, on monolayer culture (2D. We performed a direct comparison of the characteristics of the derived cardiomyocytes (iPSC-CMs on day 27 ± 2 of differentiation between 3D and 2D differentiation protocols with two different Wnt-inhibitors were compared: IWR1 (inhibitor of Wnt response or IWP2 (inhibitor of Wnt production. We firstly found that the level of Troponin T (TNNT2 expression measured by FACS was significantly higher for both 2D protocols as compared to the 3D protocol. In the three methods, iPSC-CM show sarcomeric structures. However, iPSC-CM generated in 2D protocols constantly displayed larger sarcomere lengths as compared to the 3D protocol. In addition, mRNA and protein analyses reveal higher cTNi to ssTNi ratios in the 2D protocol using IWP2 as compared to both other protocols, indicating a higher sarcomeric maturation. Differentiation of cardiac myocytes with 2D monolayer-based protocols and the use of IWP2 allows the production of higher yield of cardiac myocytes that have more suitable characteristics to study sarcomeric cardiomyopathies.

  12. Rhythmic beating of stem cell-derived cardiac cells requires dynamic coupling of electrophysiology and Ca cycling.

    Science.gov (United States)

    Zahanich, Ihor; Sirenko, Syevda G; Maltseva, Larissa A; Tarasova, Yelena S; Spurgeon, Harold A; Boheler, Kenneth R; Stern, Michael D; Lakatta, Edward G; Maltsev, Victor A

    2011-01-01

    There is an intense interest in differentiating embryonic stem cells to engineer biological pacemakers as an alternative to electronic pacemakers for patients with cardiac pacemaker function deficiency. Embryonic stem cell-derived cardiocytes (ESCs), however, often exhibit dysrhythmic excitations. Using Ca(2+) imaging and patch-clamp techniques, we studied requirements for generation of spontaneous rhythmic action potentials (APs) in late-stage mouse ESCs. Sarcoplasmic reticulum (SR) of ESCs generates spontaneous, rhythmic, wavelet-like Local Ca(2+)Releases (LCRs) (inhibited by ryanodine, tetracaine, or thapsigargin). L-type Ca(2+)current (I(CaL)) induces a global Ca(2+) release (CICR), depleting the Ca(2+) content SR which resets the phases of LCR oscillators. Following a delay, SR then generates a highly synchronized spontaneous Ca(2+)release of multiple LCRs throughout the cell. The LCRs generate an inward Na(+)/Ca(2+)exchanger (NCX) current (absent in Na(+)-free solution) that ignites the next AP. Interfering with SR Ca(2+) cycling (ryanodine, caffeine, thapsigargin, cyclopiazonic acid, BAPTA-AM), NCX (Na(+)-free solution), or I(CaL) (nifedipine) results in dysrhythmic excitations or cessation of automaticity. Inhibition of cAMP/PKA signaling by a specific PKA inhibitor, PKI, decreases SR Ca(2+) loading, substantially reducing both spontaneous LCRs (number, size, and amplitude) and rhythmic AP firing. In contrast, enhancing PKA signaling by cAMP increases the LCRs (number, size, duration) and converts irregularly beating ESCs to rhythmic "pacemaker-like" cells. SR Ca(2+) loading and LCR activity could be also increased with a selective activation of SR Ca(2+) pumping by a phospholamban antibody. We conclude that SR Ca(2+) loading and spontaneous rhythmic LCRs are driven by inherent cAMP/PKA activity. I(CaL) synchronizes multiple LCR oscillators resulting in strong, partially synchronized diastolic Ca(2+) release and NCX current. Rhythmic ESC automaticity can be

  13. Pregnancy as a cardiac stress model

    OpenAIRE

    2014-01-01

    Cardiac hypertrophy occurs during pregnancy as a consequence of both volume overload and hormonal changes. Both pregnancy- and exercise-induced cardiac hypertrophy are generally thought to be similar and physiological. Despite the fact that there are shared transcriptional responses in both forms of cardiac adaptation, pregnancy results in a distinct signature of gene expression in the heart. In some cases, however, pregnancy can induce adverse cardiac events in previously healthy women witho...

  14. Pregnancy as a cardiac stress model.

    Science.gov (United States)

    Chung, Eunhee; Leinwand, Leslie A

    2014-03-15

    Cardiac hypertrophy occurs during pregnancy as a consequence of both volume overload and hormonal changes. Both pregnancy- and exercise-induced cardiac hypertrophy are generally thought to be similar and physiological. Despite the fact that there are shared transcriptional responses in both forms of cardiac adaptation, pregnancy results in a distinct signature of gene expression in the heart. In some cases, however, pregnancy can induce adverse cardiac events in previously healthy women without any known cardiovascular disease. Peripartum cardiomyopathy is the leading cause of non-obstetric mortality during pregnancy. To understand how pregnancy can cause heart disease, it is first important to understand cardiac adaptation during normal pregnancy. This review provides an overview of the cardiac consequences of pregnancy, including haemodynamic, functional, structural, and morphological adaptations, as well as molecular phenotypes. In addition, this review describes the signalling pathways responsible for pregnancy-induced cardiac hypertrophy and angiogenesis. We also compare and contrast cardiac adaptation in response to disease, exercise, and pregnancy. The comparisons of these settings of cardiac hypertrophy provide insight into pregnancy-associated cardiac adaptation.

  15. Pregnancy as a cardiac stress model

    Science.gov (United States)

    Chung, Eunhee; Leinwand, Leslie A.

    2014-01-01

    Cardiac hypertrophy occurs during pregnancy as a consequence of both volume overload and hormonal changes. Both pregnancy- and exercise-induced cardiac hypertrophy are generally thought to be similar and physiological. Despite the fact that there are shared transcriptional responses in both forms of cardiac adaptation, pregnancy results in a distinct signature of gene expression in the heart. In some cases, however, pregnancy can induce adverse cardiac events in previously healthy women without any known cardiovascular disease. Peripartum cardiomyopathy is the leading cause of non-obstetric mortality during pregnancy. To understand how pregnancy can cause heart disease, it is first important to understand cardiac adaptation during normal pregnancy. This review provides an overview of the cardiac consequences of pregnancy, including haemodynamic, functional, structural, and morphological adaptations, as well as molecular phenotypes. In addition, this review describes the signalling pathways responsible for pregnancy-induced cardiac hypertrophy and angiogenesis. We also compare and contrast cardiac adaptation in response to disease, exercise, and pregnancy. The comparisons of these settings of cardiac hypertrophy provide insight into pregnancy-associated cardiac adaptation. PMID:24448313

  16. Paying attention to attention in recognition memory: insights from models and electrophysiology.

    Science.gov (United States)

    Dubé, Chad; Payne, Lisa; Sekuler, Robert; Rotello, Caren M

    2013-12-01

    Reliance on remembered facts or events requires memory for their sources, that is, the contexts in which those facts or events were embedded. Understanding of source retrieval has been stymied by the fact that uncontrolled fluctuations of attention during encoding can cloud results of key importance to theoretical development. To address this issue, we combined electrophysiology (high-density electroencephalogram, EEG, recordings) with computational modeling of behavioral results. We manipulated subjects' attention to an auditory attribute, whether the source of individual study words was a male or female speaker. Posterior alpha-band (8-14 Hz) power in subjects' EEG increased after a cue to ignore the voice of the person who was about to speak. Receiver-operating-characteristic analysis validated our interpretation of oscillatory dynamics as a marker of attention to source information. With attention under experimental control, computational modeling showed unequivocally that memory for source (male or female speaker) reflected a continuous signal detection process rather than a threshold recollection process.

  17. Soft tissue modelling of cardiac fibres for use in coupled mechano-electric simulations.

    Science.gov (United States)

    Whiteley, Jonathan P; Bishop, Martin J; Gavaghan, David J

    2007-10-01

    The numerical solution of the coupled system of partial differential and ordinary differential equations that model the whole heart in three dimensions is a considerable computational challenge. As a consequence, it is not computationally practical--either in terms of memory or time--to repeat simulations on a finer computational mesh to ensure that convergence of the solution has been attained. In an attempt to avoid this problem while retaining mathematical rigour, we derive a one dimensional model of a cardiac fibre that takes account of elasticity properties in three structurally defined axes within the myocardial tissue. This model of a cardiac fibre is then coupled with an electrophysiological cell model and a model of cellular electromechanics to allow us to simulate the coupling of the electrical and mechanical activity of the heart. We demonstrate that currently used numerical methods for coupling electrical and mechanical activity do not work in this case, and identify appropriate numerical techniques that may be used when solving the governing equations. This allows us to perform a series of simulations that: (i) investigate the effect of some of the assumptions inherent in other models; and (ii) reproduce qualitatively some experimental observations.

  18. Divergent electrophysiologic profile of fluconazole and voriconazole in an experimental whole-heart model of proarrhythmia.

    Science.gov (United States)

    Frommeyer, Gerrit; Fischer, Christina; Lange, Philipp S; Leitz, Patrick; Fehr, Michael; Bogossian, Harilaos; Milberg, Peter; Eckardt, Lars

    2016-04-05

    In several case reports a prolongation of the QT-interval and even proarrhythmic effects of fluconazole and voriconazole were reported. The aim of the present study was to investigate if application of fluconazole or voriconazole has the potential to provoke polymorphic ventricular tachycardia in a sensitive model of proarrhythmia. In female rabbits, fluconazole (10, 30 and 50 µM, n=6) and voriconazole (10, 30 and 50 µM, n=6) were infused after obtaining baseline data. Eight endocardial and epicardial monophasic action potentials and a simultaneously recorded 12-lead ECG showed a significant QT prolongation after application of fluconazole as compared with baseline (10 µM:+12 ms, 30 µM:+22 ms, 50 µM:+37 ms; Pfluconazole induced a significant increase (30 µM:+15 ms, 50 µM:+16 ms; Pfluconazole led to the reproducible induction of EADs in 4 of 6 hearts and polymorphic ventricular tachycardia in 3 of 6 hearts (36 episodes). In the present study, voriconazole demonstrated a safe electrophysiologic profile despite significant QT prolongation. In contrast, fluconazole led to a more marked prolongation of myocardial repolarization combined with a more marked increase of dispersion of repolarization. These results imply that application of fluconazole might be torsadogenic and the QT-interval should be closely monitored.

  19. Robotics in invasive cardiac electrophysiology.

    Science.gov (United States)

    Shurrab, Mohammed; Schilling, Richard; Gang, Eli; Khan, Ejaz M; Crystal, Eugene

    2014-07-01

    Robotic systems allow for mapping and ablation of different arrhythmia substrates replacing hand maneuvering of intracardiac catheters with machine steering. Currently there are four commercially available robotic systems. Niobe magnetic navigation system (Stereotaxis Inc., St Louis, MO) and Sensei robotic navigation system (Hansen Medical Inc., Mountain View, CA) have an established platform with at least 10 years of clinical studies looking at their efficacy and safety. AMIGO Remote Catheter System (Catheter Robotics, Inc., Mount Olive, NJ) and Catheter Guidance Control and Imaging (Magnetecs, Inglewood, CA) are in the earlier phases of implementations with ongoing feasibility and some limited clinical studies. This review discusses the advantages and limitations related to each existing system and highlights the ideal futuristic robotic system that may include the most promising features of the current ones.

  20. A new biomarker--index of cardiac electrophysiological balance (iCEB)--plays an important role in drug-induced cardiac arrhythmias: beyond QT-prolongation and Torsades de Pointes (TdPs).

    Science.gov (United States)

    Lu, Hua Rong; Yan, Gan-Xin; Gallacher, David J

    2013-01-01

    In the present study, we investigated whether a new biomarker - index of cardiac electrophysiological balance (iCEB=QT/QRS) - could predict drug-induced cardiac arrhythmias (CAs), including ventricular tachycardia/ventricular fibrillation (VT/VF) and Torsades de Pointes (TdPs). The rabbit left ventricular arterially-perfused-wedge was used to investigate whether the simple iCEB measured from the ECG is reflective of the more difficult measurement of λ (effective refractory period×conduction velocity) for predicting CAs induced by a number of drugs. Dofetilide concentration-dependently increased iCEB and λ, predicting potential risk of drug-induced incidence of early afterdepolarizations (EADs) starting at 0.01μM. Digoxin (1 and 5μM), encainide (5 and 20μM) and propoxyphene (10 and 100μM) markedly reduced both iCEB and λ, predicting their ability to induce non-TdP-like VT/VF. At 10μM, both NS1643 and levcromakalim significantly decreased λ and iCEB, which was preceded with presence of non-TdP-like VT/VF. Isoprenaline (0.05 to 0.5μM) significantly reduced both λ and iCEB, which was associated with a high incidence of non-TdP-like VT/VF in most preparations. Other biomarkers (i.e. transmural dispersion of T-wave and instability of the QT interval) predicted only dofetilide-induced long QT and EADs, but did not predict drug-induced risk of non-TdP-like VT/VF. Our data from 7 reference drugs of known pro-arrhythmic effects suggests that 1) this non-invasive iCEB predicts potential risk of drug-induced CAs beyond long QT and TdP; 2) iCEB is more useful than the current biomarkers (i.e. transmural dispersion and instability) in predicting potential risks for drug-induced non-TdP-like VT/VF. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Cardiac cell modelling: Observations from the heart of the cardiac physiome project

    KAUST Repository

    Fink, Martin

    2011-01-01

    In this manuscript we review the state of cardiac cell modelling in the context of international initiatives such as the IUPS Physiome and Virtual Physiological Human Projects, which aim to integrate computational models across scales and physics. In particular we focus on the relationship between experimental data and model parameterisation across a range of model types and cellular physiological systems. Finally, in the context of parameter identification and model reuse within the Cardiac Physiome, we suggest some future priority areas for this field. © 2010 Elsevier Ltd.

  2. Image-Based Personalization of Cardiac Anatomy for Coupled Electromechanical Modeling.

    Science.gov (United States)

    Crozier, A; Augustin, C M; Neic, A; Prassl, A J; Holler, M; Fastl, T E; Hennemuth, A; Bredies, K; Kuehne, T; Bishop, M J; Niederer, S A; Plank, G

    2016-01-01

    Computational models of cardiac electromechanics (EM) are increasingly being applied to clinical problems, with patient-specific models being generated from high fidelity imaging and used to simulate patient physiology, pathophysiology and response to treatment. Current structured meshes are limited in their ability to fully represent the detailed anatomical data available from clinical images and capture complex and varied anatomy with limited geometric accuracy. In this paper, we review the state of the art in image-based personalization of cardiac anatomy for biophysically detailed, strongly coupled EM modeling, and present our own tools for the automatic building of anatomically and structurally accurate patient-specific models. Our method relies on using high resolution unstructured meshes for discretizing both physics, electrophysiology and mechanics, in combination with efficient, strongly scalable solvers necessary to deal with the computational load imposed by the large number of degrees of freedom of these meshes. These tools permit automated anatomical model generation and strongly coupled EM simulations at an unprecedented level of anatomical and biophysical detail.

  3. Cardiac cell culture model as a left ventricle mimic for cardiac tissue generation.

    Science.gov (United States)

    Nguyen, Mai-Dung; Tinney, Joseph P; Yuan, Fangping; Roussel, Thomas J; El-Baz, Ayman; Giridharan, Guruprasad; Keller, Bradley B; Sethu, Palaniappan

    2013-09-17

    A major challenge in cardiac tissue engineering is the delivery of hemodynamic mechanical cues that play a critical role in the early development and maturation of cardiomyocytes. Generation of functional cardiac tissue capable of replacing or augmenting cardiac function therefore requires physiologically relevant environments that can deliver complex mechanical cues for cardiomyocyte functional maturation. The goal of this work is the development and validation of a cardiac cell culture model (CCCM) microenvironment that accurately mimics pressure-volume changes seen in the left ventricle and to use this system to achieve cardiac cell maturation under conditions where mechanical loads such as pressure and stretch are gradually increased from the unloaded state to conditions seen in vivo. The CCCM platform, consisting of a cell culture chamber integrated within a flow loop was created to accomplish culture of 10 day chick embryonic ventricular cardiomyocytes subject to 4 days of stimulation (10 mmHg, ∼13% stretch at a frequency of 2 Hz). Results clearly show that CCCM conditioned cardiomyocytes accelerate cardiomyocyte structural and functional maturation in comparison to static unloaded controls as evidenced by increased proliferation, alignment of actin cytoskeleton, bundle-like sarcomeric α-actinin expression, higher pacing beat rate at lower threshold voltages, and increased shortening. These results confirm the CCCM microenvironment can accelerate immature cardiac cell structural and functional maturation for potential cardiac regenerative applications.

  4. Role of breathing in cardiac performance: experimental and mathematical models

    Science.gov (United States)

    Tran, Binh Q.; Hoffman, Eric A.

    1999-05-01

    Due to the close proximity of the heart and lungs within a closed chest environment, we expect breathing to affect various cardiac performance parameters and hence cardiac output. We present an integrative approach to study heart-lung interactions, combining a mathematical formulation of the circulation system with imaging techniques using echo-planar magnetic resonance imaging (EPI) and dynamic x-ray CT (EBCT). We hypothesize that appropriate synchronization of mechanical ventilation to cardiac-cycle specific events can improve cardiac function, i.e. stroke volume (SV) and cardiac output (CO). Computational and experimental results support the notion that heart-lung interaction, leading to altered cardiac output associated with inspiration/expiration, is not directly associated with lung inflation/deflation and thus is felt to be more influenced by pleural pressure changes. The mathematical model of the circulation demonstrates the importance of cardiac-cycle specific timing of ventilation on cardiac function and matches with experimentally observed relationships found in animal models studied via EBCT and human studies using EPI. Results show that positive pressure mechanical ventilation timed to systolic events may increase SV and CO by up to 30%, mainly by increased filling of the ventricles during diastole. Similarly, negative pressure (spontaneous) respiration has its greatest effect on ventricular diastolic filling. Cardiac-gated mechanical ventilation may provide sufficient cardiac augmentation to warrant further investigation as a minimally-invasive technique for temporary cardiac assist. Through computational modeling and advanced imaging protocols, we were able to uniquely study heart-lung interactions within the intact milieu of the never-invaded thorax.

  5. 面向短 QT 综合征的电生理建模与仿真研究进展%Research Advance on the Electrophysiological Modeling and Simulation of Short QT Syndrome

    Institute of Scientific and Technical Information of China (English)

    罗存金; 王宽全; 袁永峰; 吕伟刚; Henggui Zhang

    2015-01-01

    近年来,多物理尺度建模仿真心电动力学研究已经取得了显著进展。本文介绍当前心脏建模仿真领域中心肌细胞钾离子通道基因突变引起短QT综合征的研究情况。首先从Denis Noble多物理尺度划分的角度介绍了亚细胞与细胞级模型、心肌纤维与组织级模型、心脏器官级模型以及仿真心电图等数学模型,并从量化的角度来分析短QT综合征基因变异在细胞、组织、器官等多层面上对心电功能的影响;然后重点列出了三种短QT综合征亚型近期的研究成果;最后进一步探讨了面向短QT综合征的电生理建模与仿真的研究方向和应用前景。%Multi-physical scale modeling for simulating the electrophysiological dynamics of the heart is rapidly evolving and has made significant progress in the last decade .In this paper ,we briefly review the current development of cardiac modeling field with a particular focus on the modeling of short QT (SQT )syndrome arising from gene mutations in cardiac potassium channels . Firstly ,we introduce Denis Noble’s definition on multi-physical scale modeling of cardiac systems at sub-cellular ,cellular ,tissue and whole organ levels .Secondly ,we describe quantities that have been used to characterize the functional impacts of SQT gene muta-tions on the electrical activity of cardiac systems at cellular ,tissue and whole organ levels .Then we review up-to-date research re-sults on quantifying the functional impacts of three SQT gene mutations associated with potassium channels on the genesis of cardiac arrhythmia that underlie cardiac sudden death .Finally we outline possible research and application prospects of the electrophysi-ological modeling and simulation of SQT syndrome in the future .

  6. FPGA in-the-loop simulations of cardiac excitation model under voltage clamp conditions

    Science.gov (United States)

    Othman, Norliza; Adon, Nur Atiqah; Mahmud, Farhanahani

    2017-01-01

    Voltage clamp technique allows the detection of single channel currents in biological membranes in identifying variety of electrophysiological problems in the cellular level. In this paper, a simulation study of the voltage clamp technique has been presented to analyse current-voltage (I-V) characteristics of ion currents based on Luo-Rudy Phase-I (LR-I) cardiac model by using a Field Programmable Gate Array (FPGA). Nowadays, cardiac models are becoming increasingly complex which can cause a vast amount of time to run the simulation. Thus, a real-time hardware implementation using FPGA could be one of the best solutions for high-performance real-time systems as it provides high configurability and performance, and able to executes in parallel mode operation. For shorter time development while retaining high confidence results, FPGA-based rapid prototyping through HDL Coder from MATLAB software has been used to construct the algorithm for the simulation system. Basically, the HDL Coder is capable to convert the designed MATLAB Simulink blocks into hardware description language (HDL) for the FPGA implementation. As a result, the voltage-clamp fixed-point design of LR-I model has been successfully conducted in MATLAB Simulink and the simulation of the I-V characteristics of the ionic currents has been verified on Xilinx FPGA Virtex-6 XC6VLX240T development board through an FPGA-in-the-loop (FIL) simulation.

  7. "Just-In-Time" Simulation Training Using 3-D Printed Cardiac Models After Congenital Cardiac Surgery.

    Science.gov (United States)

    Olivieri, Laura J; Su, Lillian; Hynes, Conor F; Krieger, Axel; Alfares, Fahad A; Ramakrishnan, Karthik; Zurakowski, David; Marshall, M Blair; Kim, Peter C W; Jonas, Richard A; Nath, Dilip S

    2016-03-01

    High-fidelity simulation using patient-specific three-dimensional (3D) models may be effective in facilitating pediatric cardiac intensive care unit (PCICU) provider training for clinical management of congenital cardiac surgery patients. The 3D-printed heart models were rendered from preoperative cross-sectional cardiac imaging for 10 patients undergoing congenital cardiac surgery. Immediately following surgical repair, a congenital cardiac surgeon and an intensive care physician conducted a simulation training session regarding postoperative care utilizing the patient-specific 3D model for the PCICU team. After the simulation, Likert-type 0 to 10 scale questionnaire assessed participant perception of impact of the training session. Seventy clinicians participated in training sessions, including 22 physicians, 38 nurses, and 10 ancillary care providers. Average response to whether 3D models were more helpful than standard hand off was 8.4 of 10. Questions regarding enhancement of understanding and clinical ability received average responses of 9.0 or greater, and 90% of participants scored 8 of 10 or higher. Nurses scored significantly higher than other clinicians on self-reported familiarity with the surgery (7.1 vs. 5.8; P = .04), clinical management ability (8.6 vs. 7.7; P = .02), and ability enhancement (9.5 vs. 8.7; P = .02). Compared to physicians, nurses and ancillary providers were more likely to consider 3D models more helpful than standard hand off (8.7 vs. 7.7; P = .05). Higher case complexity predicted greater enhancement of understanding of surgery (P = .04). The 3D heart models can be used to enhance congenital cardiac critical care via simulation training of multidisciplinary intensive care teams. Benefit may be dependent on provider type and case complexity. © The Author(s) 2016.

  8. Influence of Wenxin particle on cardiac electrophysiology in depressed rats after myocardial infarction%稳心颗粒对心肌梗死后抑郁大鼠心脏电生理的影响

    Institute of Scientific and Technical Information of China (English)

    梁锦军; 黄从新; 石少波; 谌晶晶; 王芳; 谌莹莹; 袁晓冉; 曲川; 黄鹤; 杨波

    2012-01-01

    目的:运用稳心颗粒干预心肌梗死后合并抑郁大鼠,探讨其对心梗后抑郁大鼠心脏电生理的影响.方法:选择SD大鼠50只,均分为正常组,心梗组,抑郁组,心梗后抑郁组(模型组)和稳心颗粒干预组(以2g/d的稳心颗粒给模型组大鼠灌胃28d).先后急性结扎左冠脉和予以慢性不可控的温和应激,制作心肌梗死后抑郁模型大鼠,予稳心颗粒干预,评价其对模型大鼠在体单向动作电位(MAP90)、左室有效不应期(ERP)和室颤阈值(VFT)等电生理学指标的影响.结果:(1)与正常组相比,模型组行为学评分有显著下降(P<0.05),经过4周稳心颗粒治疗后,其行为学评分显著上升(P<0.01);(2)与正常组相比,模型组MAPD90和ERP明显延长,VFT明显降低(P<0.05);稳心颗粒干预后,与模型组比较,稳心颗粒组MAPD90[(89.33±7.12)ms比(72.29±8.37)ms]、ERP[(84.00±6.57) ms比(68.00±7.43)ms]明显缩短,VFT[(7±3.11)V比(29±5.60) V]明显升高(P<0.05).结论:稳心颗粒能改善心肌梗死后抑郁大鼠心脏电重构,包括缩短单向动作电位和左室有效不应期,增加室颤阈值.%Objective:To investigate influence of Wenxin particle on cardiac electrophysiology in rats complicated with depression after myocardial infarction (MI).Methods:A total of 50 SD rats were randomly and equally divided into normal group,MI group,depression group,MI complicated depression group (modeI group) and Wenxin particle group (Wenxin particle were given to model rats by gavage,2 g/d,28d).Model (MI complicated with depresion) rats were made by acute ligation of left coronary artery and supply chronic unpredictable mild stress in order.The influences of wencin particle on cardiac electrophysiological indexes,such as monophasic action potential (MAP90),left ventricular effective refractory period (ERP) and ventricular fibrillation threshold (VFT) were evaluated in wencin particle group.Results:(1) Compared with normal group,there were

  9. Cardiac Dysfunction in a Porcine Model of Pediatric Malnutrition

    DEFF Research Database (Denmark)

    Fabiansen, Christian; Lykke, Mikkel; Hother, Anne-Louise

    2015-01-01

    BACKGROUND: Half a million children die annually of severe acute malnutrition and cardiac dysfunction may contribute to the mortality. However, cardiac function remains poorly examined in cases of severe acute malnutrition. OBJECTIVE: To determine malnutrition-induced echocardiographic disturbances...... and longitudinal changes in plasma pro-atrial natriuretic peptide and cardiac troponin-T in a pediatric porcine model. METHODS AND RESULTS: Five-week old piglets (Duroc-x-Danish Landrace-x-Yorkshire) were fed a nutritionally inadequate maize-flour diet to induce malnutrition (MAIZE, n = 12) or a reference diet...... groups. The myocardial performance index was 86% higher in MAIZE vs AGE-REF (pMalnutrition associates with cardiac dysfunction in a pediatric porcine model by increased myocardial performance index and pro-atrial natriuretic peptide...

  10. Gap junction remodeling and cardiac arrhythmogenesis in a murine model of oculodentodigital dysplasia.

    Science.gov (United States)

    Kalcheva, Nellie; Qu, Jiaxiang; Sandeep, Nefthi; Garcia, Luis; Zhang, Jie; Wang, Zhiyong; Lampe, Paul D; Suadicani, Sylvia O; Spray, David C; Fishman, Glenn I

    2007-12-18

    Gap junction channels are required for normal cardiac impulse propagation, and gap junction remodeling is associated with enhanced arrhythmic risk. Oculodentodigital dysplasia (ODDD) is a multisystem syndrome due to mutations in the connexin43 (Cx43) gap junction channel gene. To determine the effects of a human connexin channelopathy on cardiac electrophysiology and arrhythmogenesis, we generated a murine model of ODDD by introducing the disease-causing I130T mutant allele into the mouse genome. Cx43 abundance was markedly reduced in mutant hearts with preferential loss of phosphorylated forms that interfered with trafficking and assembly of gap junctions in the junctional membrane. Dual whole-cell patch-clamp studies showed significantly lower junctional conductance between neonatal cell pairs from mutant hearts, and optical mapping of isolated-perfused hearts with voltage-sensitive dyes demonstrated significant slowing of conduction velocity. Programmed electrical stimulation revealed a markedly increased susceptibility to spontaneous and inducible ventricular tachyarrhythmias. In summary, our data demonstrate that the I130T mutation interferes with Cx43 posttranslational processing, resulting in diminished cell-cell coupling, slowing of impulse propagation, and a proarrhythmic substrate.

  11. Images as drivers of progress in cardiac computational modelling.

    Science.gov (United States)

    Lamata, Pablo; Casero, Ramón; Carapella, Valentina; Niederer, Steve A; Bishop, Martin J; Schneider, Jürgen E; Kohl, Peter; Grau, Vicente

    2014-08-01

    Computational models have become a fundamental tool in cardiac research. Models are evolving to cover multiple scales and physical mechanisms. They are moving towards mechanistic descriptions of personalised structure and function, including effects of natural variability. These developments are underpinned to a large extent by advances in imaging technologies. This article reviews how novel imaging technologies, or the innovative use and extension of established ones, integrate with computational models and drive novel insights into cardiac biophysics. In terms of structural characterization, we discuss how imaging is allowing a wide range of scales to be considered, from cellular levels to whole organs. We analyse how the evolution from structural to functional imaging is opening new avenues for computational models, and in this respect we review methods for measurement of electrical activity, mechanics and flow. Finally, we consider ways in which combined imaging and modelling research is likely to continue advancing cardiac research, and identify some of the main challenges that remain to be solved.

  12. Cardiac dysfunction in a porcine model of pediatric malnutrition

    DEFF Research Database (Denmark)

    Fabiansen, Christian; Lykke, Mikkel; Nielsen, Anne-Louise Hother;

    2015-01-01

    and longitudinal changes in plasma pro-atrial natriuretic peptide and cardiac troponin-T in a pediatric porcine model. METHODS AND RESULTS: Five-week old piglets (Duroc-x-Danish Landrace-x-Yorkshire) were fed a nutritionally inadequate maize-flour diet to induce malnutrition (MAIZE, n = 12) or a reference diet......BACKGROUND: Half a million children die annually of severe acute malnutrition and cardiac dysfunction may contribute to the mortality. However, cardiac function remains poorly examined in cases of severe acute malnutrition. OBJECTIVE: To determine malnutrition-induced echocardiographic disturbances...... (AGE-REF, n = 12) for 7 weeks. Outcomes were compared to a weight-matched reference group (WEIGHT-REF, n = 8). Pro-atrial natriuretic peptide and cardiac troponin-T were measured weekly. Plasma pro-atrial natriuretic peptide decreased in both MAIZE and AGE-REF during the first 3 weeks but increased...

  13. CAPSAICIN SUPPLEMENTATION FAILS TO MODULATE AUTONOMIC AND CARDIAC ELECTROPHYSIOLOGIC ACTIVITY DURING EXERCISE IN THE OBESE: WITH VARIANTS OF UCP2 AND UCP3 POLYMORPHISM

    Directory of Open Access Journals (Sweden)

    Ki Ok Shin

    2008-09-01

    Full Text Available We investigated the effects of capsaicin supplementation (150mg on alterations of autonomic nervous system (ANS activity associated with adverse effects of cardiac depolarization-repolarization intervals during aerobic exercise in obese humans. Nine obese males (26.1 ± 1.5 yrs volunteered between study designed. The cardiac ANS activities evaluated by means of heart rate variability of power spectral analysis and cardiac QT interval were continuously measured during 5-min rest and 30-min exercise at 50% of maximal ventilation threshold (50%VTmax on stationary ergometer with placebo (CON or capsaicin (CAP oral administration chosen at random. The uncoupling protein (UCP 2 and UCP 3 genetic variants of the subjects were analyzed by noninvasive genotyping method from collecting buccal mucosa cells. The results indicated that there were no significant differences in cardiac ANS activities during rest and exercise between CON and CAP trials. Although no significant difference, A/A allele of UCP2 polymorphism showed a reduced sympathetic nervous system (SNS index activity compared to G/G + G/A allele during exercise intervention in our subjects. On the other hand, the data on cardiac QT interval showed no significant difference, indicating that oral administration of capsaicin did not cause any adverse effect on cardiac depolarization-repolarization. In conclusion, our results suggest that capsaicin supplementation 1 h before exercise intervention has no effect on cardiac ANS activities and cardiac electrical stability during exercise in obese individuals. Further studies should also consider genetic variants for exercise efficacy against obesity

  14. T3 and cardiac myocyte cell: a theoretical model.

    Science.gov (United States)

    Athanasios, Tsatsaris; Antonios, Baldoukas; Antonios, Loumousiotis; Eustathios, Koukounaris; Maria, Giota; Despina, Perrea

    2013-08-01

    In the last decades, the outstanding role of Thyroid gland in regulating both physiological and pathological operation of cardiovascular system has been acknowledged worldwide. Three main domains of Thyroid function, that is to say, euthyroidism -hyperthyroidism-hypothyroidism, have a direct impact on cardiac response through a variety of mechanisms. Cellular pathways mediate in cardiac contractility, cardiac output, cardiac rhythm, arterial blood pressure and peripheral vessel resistance. Particular biochemical algorithms exist not only between Thyroid hormones' serum concentration and thyroid gland but also between the hormones' serum level and heart muscle genes. These biochemical pathways primarily regulate the appropriate secretion of levothyroxine (T4) and triiodothyronine(T3) via Thyroid- Stimulating-Hormone(TSH) pituitary system, and secondly adjust the cardiac function. In this study, a mathematic model has been developed describing significant aspects of positive or negative feedback mechanisms of THYRO-CARDIAC (THY-CAR) system along with potential applications of novel up-to-date patents in this area of research.

  15. Electrophysiology of living organs from first principles

    CERN Document Server

    Scharf, Günter

    2010-01-01

    Based on the derivation of the macroscopic Maxwell's equations by spatial averaging of the microscopic equations, we discuss the electrophysiology of living organs. Other methods of averaging (or homogenization) like the bidomain model are not compatible with Maxwell's theory. We also point out that modeling the active cells by source currents is not a suitable description of the situation from first principles. Instead, it turns out that the main source of the measured electrical potentials is the polarization charge density which exists at the membranes of the active cells and adds up to a macroscopic polarization. The latter is the source term in the Laplace equation, the solution of which gives the measured far-field potential. As a consequence it is the polarization or dipole density which is best suited for localization of cardiac arrhythmia.

  16. Characterization of Cardiac Patients Based on the Synergy Model

    Directory of Open Access Journals (Sweden)

    Tavangar

    2014-10-01

    Full Text Available Background Cardiac patients need comprehensive support due to the adverse effects of this disease on different aspects of their lives. Synergy intervention is a model that focuses on patients' requirements. Objectives This study aimed to determine the eightfold characteristic of cardiac patients based on the synergy model that represent their clinical requirements. Materials and Methods In this descriptive cross-sectional study, 40 cardiac patients hospitalized at the cardiac care unit (CCU of Yazd Afshar Hospital were randomly selected. The data were collected by using a two-part check-list including demographic characteristics and also by studying eight characteristics of patients through interviewing and reviewing their records. The results were analyzed using descriptive statistics such as frequency (percentage and analytical statistics such as Spearman and Mann-Whitney test with the SPSS software, version 18. Results The results showed that among patients' internal characteristics, reversibility (70.6%, vulnerability (68.6%, and predictability (80.4% at level 1 (the minimum score had the highest frequency and stability (49% and complexity (54.9% were at level 3 (average score. Among external characteristics participation in decision-making (80.4% at level 1 had the highest frequency while care (62.7% and recourses (98% were at level 3. Conclusions Ignoring any of the eightfold characteristics based on the synergy model interferes with comprehensive support of cardiac patients. Therefore, it is necessary for professional health practitioners, especially nurses, to consider patients' eightfold characteristics in order to provide quality care.

  17. Cardiac Dysfunction in a Porcine Model of Pediatric Malnutrition.

    Directory of Open Access Journals (Sweden)

    Christian Fabiansen

    Full Text Available Half a million children die annually of severe acute malnutrition and cardiac dysfunction may contribute to the mortality. However, cardiac function remains poorly examined in cases of severe acute malnutrition.To determine malnutrition-induced echocardiographic disturbances and longitudinal changes in plasma pro-atrial natriuretic peptide and cardiac troponin-T in a pediatric porcine model.Five-week old piglets (Duroc-x-Danish Landrace-x-Yorkshire were fed a nutritionally inadequate maize-flour diet to induce malnutrition (MAIZE, n = 12 or a reference diet (AGE-REF, n = 12 for 7 weeks. Outcomes were compared to a weight-matched reference group (WEIGHT-REF, n = 8. Pro-atrial natriuretic peptide and cardiac troponin-T were measured weekly. Plasma pro-atrial natriuretic peptide decreased in both MAIZE and AGE-REF during the first 3 weeks but increased markedly in MAIZE relative to AGE-REF during week 5-7 (p ≤ 0.001. There was overall no difference in plasma cardiac troponin-T between groups. However, further analysis revealed that release of cardiac troponin-T in plasma was more frequent in AGE-REF compared with MAIZE (OR: 4.8; 95%CI: 1.2-19.7; p = 0.03. However, when release occurred, cardiac troponin-T concentration was 6.9-fold higher (95%CI: 3.0-15.9; p < 0.001 in MAIZE compared to AGE-REF. At week 7, the mean body weight in MAIZE was lower than AGE-REF (8.3 vs 32.4 kg, p < 0.001, whereas heart-weight relative to body-weight was similar across the three groups. The myocardial performance index was 86% higher in MAIZE vs AGE-REF (p < 0.001 and 27% higher in MAIZE vs WEIGHT-REF (p = 0.025.Malnutrition associates with cardiac dysfunction in a pediatric porcine model by increased myocardial performance index and pro-atrial natriuretic peptide and it associates with cardiac injury by elevated cardiac troponin-T. Clinical studies are needed to see if the same applies for children suffering from malnutrition.

  18. Modern perspectives on numerical modeling of cardiac pacemaker cell.

    Science.gov (United States)

    Maltsev, Victor A; Yaniv, Yael; Maltsev, Anna V; Stern, Michael D; Lakatta, Edward G

    2014-01-01

    Cardiac pacemaking is a complex phenomenon that is still not completely understood. Together with experimental studies, numerical modeling has been traditionally used to acquire mechanistic insights in this research area. This review summarizes the present state of numerical modeling of the cardiac pacemaker, including approaches to resolve present paradoxes and controversies. Specifically we discuss the requirement for realistic modeling to consider symmetrical importance of both intracellular and cell membrane processes (within a recent "coupled-clock" theory). Promising future developments of the complex pacemaker system models include the introduction of local calcium control, mitochondria function, and biochemical regulation of protein phosphorylation and cAMP production. Modern numerical and theoretical methods such as multi-parameter sensitivity analyses within extended populations of models and bifurcation analyses are also important for the definition of the most realistic parameters that describe a robust, yet simultaneously flexible operation of the coupled-clock pacemaker cell system. The systems approach to exploring cardiac pacemaker function will guide development of new therapies such as biological pacemakers for treating insufficient cardiac pacemaker function that becomes especially prevalent with advancing age.

  19. Modern Perspectives on Numerical Modeling of Cardiac Pacemaker Cell

    Science.gov (United States)

    Maltsev, Victor A.; Yaniv, Yael; Maltsev, Anna V.; Stern, Michael D.; Lakatta, Edward G.

    2015-01-01

    Cardiac pacemaking is a complex phenomenon that is still not completely understood. Together with experimental studies, numerical modeling has been traditionally used to acquire mechanistic insights in this research area. This review summarizes the present state of numerical modeling of the cardiac pacemaker, including approaches to resolve present paradoxes and controversies. Specifically we discuss the requirement for realistic modeling to consider symmetrical importance of both intracellular and cell membrane processes (within a recent “coupled-clock” theory). Promising future developments of the complex pacemaker system models include the introduction of local calcium control, mitochondria function, and biochemical regulation of protein phosphorylation and cAMP production. Modern numerical and theoretical methods such as multi-parameter sensitivity analyses within extended populations of models and bifurcation analyses are also important for the definition of the most realistic parameters that describe a robust, yet simultaneously flexible operation of the coupled-clock pacemaker cell system. The systems approach to exploring cardiac pacemaker function will guide development of new therapies, such as biological pacemakers for treating insufficient cardiac pacemaker function that becomes especially prevalent with advancing age. PMID:24748434

  20. Simulation study of a magnetocardiogram based on a virtual heart model: effect of a cardiac equivalent source and a volume conductor

    Institute of Scientific and Technical Information of China (English)

    Shou Guo-Fa; Xia Ling; Ma Ping; Tang Fa-Kuan; Dai Ling

    2011-01-01

    In this paper, we present a magnetocardiogram (MCG) simulation study using the boundary element method (BEM) and based on the virtual heart model and the realistic human volume conductor model. The different contributions of cardiac equivalent source models and volume conductor models to the MCG are deeply and comprehensively investigated. The single dipole source model, the multiple dipoles source model and the equivalent double layer (EDL) source model are analysed and compared with the cardiac equivalent source models. Meanwhile, the effect of the volume conductor model on the MCG combined with these cardiac equivalent sources is investigated. The simulation results demonstrate that the cardiac electrophysiological information will be partly missed when only the single dipole source is taken, while the EDL source is a good option for MCG simulation and the effect of the volume conductor is smallest for the EDL source. Therefore, the EDL source is suitable for the study of MCG forward and inverse problems, and more attention should be paid to it in future MCG studies.

  1. Block of GABA(A) receptor ion channel by penicillin: electrophysiological and modeling insights toward the mechanism.

    Science.gov (United States)

    Rossokhin, Alexey V; Sharonova, Irina N; Bukanova, Julia V; Kolbaev, Sergey N; Skrebitsky, Vladimir G

    2014-11-01

    GABA(A) receptors (GABA(A)R) mainly mediate fast inhibitory neurotransmission in the central nervous system. Different classes of modulators target GABA(A)R properties. Penicillin G (PNG) belongs to the class of noncompetitive antagonists blocking the open GABA(A)R and is a prototype of β-lactam antibiotics. In this study, we combined electrophysiological and modeling approaches to investigate the peculiarities of PNG blockade of GABA-activated currents recorded from isolated rat Purkinje cells and to predict the PNG binding site. Whole-cell patch-сlamp recording and fast application system was used in the electrophysiological experiments. PNG block developed after channel activation and increased with membrane depolarization suggesting that the ligand binds within the open channel pore. PNG blocked stationary component of GABA-activated currents in a concentration-dependent manner with IC50 value of 1.12mM at -70mV. The termination of GABA and PNG co-application was followed by a transient tail current. Protection of the tail current from bicuculline block and dependence of its kinetic parameters on agonist affinity suggest that PNG acts as a sequential open channel blocker that prevents agonist dissociation while the channel remains blocked. We built the GABA(A)R models based on nAChR and GLIC structures and performed an unbiased systematic search of the PNG binding site. Monte-Carlo energy minimization was used to find the lowest energy binding modes. We have shown that PNG binds close to the intracellular vestibule. In both models the maximum contribution to the energy of ligand-receptor interactions revealed residues located on the level of 2', 6' and 9' rings formed by a bundle of M2 transmembrane segments, indicating that these residues most likely participate in PNG binding. The predicted structural models support the described mechanism of PNG block.

  2. Reentry produced by small-scale heterogeneities in a discrete model of cardiac tissue

    Science.gov (United States)

    Alonso, Sergio; Bär, Markus

    2016-06-01

    Reentries are reexcitations of cardiac tissue after the passing of an excitation wave which can cause dangerous arrhythmias like tachycardia or life-threatening heart failures like fibrillation. The heart is formed by a network of cells connected by gap junctions. Under ischemic conditions some of the cells lose their connections, because gap junctions are blocked and the excitability is decreased. We model a circular region of the tissue where a fraction of connections among individual cells are removed and substituted by non-conducting material in a two-dimensional (2D) discrete model of a heterogeneous excitable medium with local kinetics based on electrophysiology. Thus, two neighbouring cells are connected (disconnected) with a probability ϕ (1 - ϕ). Such a region is assumed to be surrounded by homogeneous tissue. The circular heterogeneous area is shown to act as a source of new waves which reenter into the tissue and reexcitate the whole domain. We employ the Fenton-Karma equations to model the action potential for the local kinetics of the discrete nodes to study the statistics of the reentries in two dimensional networks with different topologies. We conclude that the probability of reentry is determined by the proximity of the fraction of disrupted connections between neighboring nodes (“cells”) in the heterogeneous region to the percolation threshold.

  3. Qualitative Analysis for Rheodynamic Model of Cardiac Pressure Pulsations

    Institute of Scientific and Technical Information of China (English)

    Zhi-cong Liu; Bei-ye Feng

    2004-01-01

    In this paper,we give a rigorous mathematical and complete parameter analysis for the rheodynamic model of cardiac and obtain the conditions and parameter region for global existence and uniqueness of limit cycle and the global bifurcation diagram of limit cycles.We also discuss the resonance phenomenons of the perturbed system.

  4. Mouse models of SCN5A-related cardiac arrhythmias

    Directory of Open Access Journals (Sweden)

    Flavien eCharpentier

    2012-06-01

    Full Text Available Mutations of SCN5A gene, which encodes the α-subunit of the voltage-gated Na+ channel NaV1.5, underlie hereditary cardiac arrhythmic syndromes such as the type 3 long QT syndrome, cardiac conduction diseases, the Brugada syndrome, the sick sinus syndrome, atrial standstill and numerous overlap syndromes. Patch-clamp studies in heterologous expression systems have provided important information to understand the genotype-phenotype relationships of these diseases. However, they could not clarify how SCN5A mutations can be responsible for such a large spectrum of diseases, for the late age of onset or the progressiveness of some of these diseases and for the overlapping syndromes. Genetically modified mice rapidly appeared as promising tools for understanding the pathophysiological mechanisms of cardiac SCN5A-related arrhythmic syndromes and several mouse models have been established. This paper reviews some of the results obtained on these models that, for most of them, recapitulate the clinical phenotypes of the patients. It also points out that these models also have their own limitations. Overall, mouse models appear as powerful tools to elucidate the pathophysiological mechanisms of SCN5A-related diseases and offer the opportunity to investigate the secondary cellular consequences of SCN5A mutations such as the expression remodelling of other genes that might participate to the overall phenotype. Finally, they constitute useful tools for addressing the role of genetic and environmental modifiers on cardiac electrical activity.

  5. Cardiac motion compensation and resolution modeling in simultaneous PET-MR: a cardiac lesion detection study

    Science.gov (United States)

    Petibon, Y.; Ouyang, J.; Zhu, X.; Huang, C.; Reese, T. G.; Chun, S. Y.; Li, Q.; El Fakhri, G.

    2013-04-01

    Cardiac motion and partial volume effects (PVE) are two of the main causes of image degradation in cardiac PET. Motion generates artifacts and blurring while PVE lead to erroneous myocardial activity measurements. Newly available simultaneous PET-MR scanners offer new possibilities in cardiac imaging as MRI can assess wall contractility while collecting PET perfusion data. In this perspective, we develop a list-mode iterative reconstruction framework incorporating both tagged-MR derived non-rigid myocardial wall motion and position dependent detector point spread function (PSF) directly into the PET system matrix. In this manner, our algorithm performs both motion ‘deblurring’ and PSF deconvolution while reconstructing images with all available PET counts. The proposed methods are evaluated in a beating non-rigid cardiac phantom whose hot myocardial compartment contains small transmural and non-transmural cold defects. In order to accelerate imaging time, we investigate collecting full and half k-space tagged MR data to obtain tagged volumes that are registered using non-rigid B-spline registration to yield wall motion information. Our experimental results show that tagged-MR based motion correction yielded an improvement in defect/myocardium contrast recovery of 34-206% as compared to motion uncorrected studies. Likewise, lesion detectability improved by respectively 115-136% and 62-235% with MR-based motion compensation as compared to gating and no motion correction and made it possible to distinguish non-transmural from transmural defects, which has clinical significance given the inherent limitations of current single modality imaging in identifying the amount of residual ischemia. The incorporation of PSF modeling within the framework of MR-based motion compensation significantly improved defect/myocardium contrast recovery (5.1-8.5%, p defect detectability (39-56%, p < 0.01). No statistical difference was found in PET contrast and lesion detectability

  6. Gallic acid improved behavior, brain electrophysiology, and inflammation in a rat model of traumatic brain injury.

    Science.gov (United States)

    Sarkaki, Alireza; Farbood, Yaghoub; Gharib-Naseri, Mohammad Kazem; Badavi, Mohammad; Mansouri, Mohammad Taghi; Haghparast, Abbas; Mirshekar, Mohammad Ali

    2015-08-01

    Traumatic brain injury (TBI) is one of the main causes of intellectual and cognitive disabilities. In the clinic it is essential to limit the development of cognitive impairment after TBI. In this study, the effects of gallic acid (GA; 100 mg/kg, per oral, from 7 days before to 2 days after TBI induction) on neurological score, passive avoidance memory, long-term potentiation (LTP) deficits, and levels of proinflammatory cytokines including interleukin-1 beta (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) in the brain have been evaluated. Brain injury was induced following Marmarou's method. Data were analyzed by one-way and repeated measures ANOVA followed by Tukey's post-hoc test. The results indicated that memory was significantly impaired (p memory and LTP in the TBI rats. The brain tissue levels of IL-1β, IL-6, and TNF-α were significantly reduced (p electrophysiological, and inflammatory disorders, probably via the decrease of cerebral proinflammatory cytokines.

  7. Towards an integrative computational model of the guinea pig cardiac myocyte

    Directory of Open Access Journals (Sweden)

    Laura Doyle Gauthier

    2012-07-01

    Full Text Available The local control theory of excitation-contraction (EC coupling asserts that regulation of calcium (Ca2+ release occurs at the nanodomain level, where openings of single L-type Ca2+ channels (LCCs trigger openings of small clusters of ryanodine receptors (RyRs co-localized within the dyad. A consequence of local control is that the whole-cell Ca2+ transient is a smooth continuous function of influx of Ca2+ through LCCs. While this so-called graded release property has been known for some time, it’s functional importance to the integrated behavior of the cardiac ventricular myocyte has not been fully appreciated. We previously formulated a biophysically-based model, in which LCCs and RyRs interact via a coarse-grained representation of the dyadic space. The model captures key features of local control using a low-dimensional system of ordinary differential equations. Voltage-dependent gain and graded Ca2+ release are emergent properties of this model by virtue of the fact that model formulation is closely based on the sub-cellular basis of local control. In this current work, we have incorporated this graded release model into a prior model of guinea pig ventricular myocyte electrophysiology, metabolism, and isometric force production. The resulting integrative model predicts the experimentally-observed causal relationship between action potential (AP shape and timing of Ca2+ and force transients, a relationship that is not explained by models lacking the graded release property. Model results suggest that even relatively subtle changes in AP morphology that may result, for example, from remodeling of membrane transporter expression in disease or spatial variation in cell properties, may have major impact on the temporal waveform of Ca2+ transients, thus influencing tissue-level electro-mechanical function.

  8. Exercise-Based Oncology Rehabilitation: Leveraging the Cardiac Rehabilitation Model

    Science.gov (United States)

    Dittus, Kim L.; Lakoski, Susan G.; Savage, Patrick D.; Kokinda, Nathan; Toth, Michael; Stevens, Diane; Woods, Kimberly; O’Brien, Patricia; Ades, Philip A.

    2014-01-01

    PURPOSE The value of exercise and rehabilitative interventions for cancer survivors is increasingly clear and oncology rehabilitation programs could provide these important interventions. However, a pathway to create oncology rehabilitation has not been delineated. Community-based cardiac rehabilitation (CR) programs staffed by health care professionals with experience in providing rehabilitation and secondary prevention services to individuals with coronary heart disease are widely available and provide a potential model and location for oncology rehabilitation programs. Our purpose is to outline the rehabilitative needs of cancer survivors and demonstrate how oncology rehabilitation can be created using a cardiac rehabilitation model. METHODS We identify the impairments associated with cancer and its therapy that respond to rehabilitative interventions. Components of the CR model that would benefit cancer survivors are described. An example of an oncology rehabilitation program using a CR model is presented. RESULTS Cancer survivors have impairments associated with cancer and its therapy that improve with rehabilitation. Our experience demonstrates that effective rehabilitation services can be provided utilizing an existing CR infrastructure. Few adjustments to current cardiac rehabilitation models would be needed to provide oncology rehabilitation. Preliminary evidence suggests that cancer survivors participating in an oncology rehabilitation program experience improvements in psychological and physiologic parameters. CONCLUSIONS Utilizing the CR model of rehabilitative services and disease management provides a much needed mechanism to bring oncology rehabilitation to larger numbers of cancer survivors. PMID:25407596

  9. Cardiac modeling using active appearance models and morphological operators

    Science.gov (United States)

    Pfeifer, Bernhard; Hanser, Friedrich; Seger, Michael; Hintermueller, Christoph; Modre-Osprian, Robert; Fischer, Gerald; Muehlthaler, Hannes; Trieb, Thomas; Tilg, Bernhard

    2005-04-01

    We present an approach for fast reconstructing of cardiac myocardium and blood masses of a patient's heart from morphological image data, acquired either MRI or CT, in order to estimate numerically the spread of electrical excitation in the patient's atria and ventricles. The approach can be divided into two main steps. During the first step the ventricular and atrial blood masses are extracted employing Active Appearance Models (AAM). The left and right ventricular blood masses are segmented automatically after providing the positions of the apex cordis and the base of the heart. Because of the complex geometry of the atria the segmentation process of the atrial blood masses requires more information as the ventricular blood mass segmentation process of the ventricles. We divided, for this reason, the left and right atrium into three divisions of appearance. This proved sufficient for the 2D AAM model to extract the target blood masses. The base of the heart, the left upper and left lower pulmonary vein from its first up to its last appearance in the image stack, and the right upper and lower pulmonary vein have to be marked. After separating the volume data into these divisions the 2D AAM search procedure extracts the blood masses which are the main input for the second and last step in the myocardium extraction pipeline. This step uses morphologically-based operations in order to extract the ventricular and atrial myocardium either directly by detecting the myocardium in the volume block or by reconstructing the myocardium using mean model information, in case the algorithm fails to detect the myocardium.

  10. Cardiac disease modeling using induced pluripotent stemcell-derived human cardiomyocytes

    Institute of Scientific and Technical Information of China (English)

    Patrizia Dell’Era; Patrizia Benzoni; Elisabetta Crescini; Matteo Valle; Er Xia; Antonella Consiglio; Maurizio Memo

    2015-01-01

    Causative mutations and variants associated with cardiacdiseases have been found in genes encoding cardiac ionchannels, accessory proteins, cytoskeletal components,junctional proteins, and signaling molecules. In mostcases the functional evaluation of the genetic alterationhas been carried out by expressing the mutated proteinsin in-vitro heterologous systems. While these studieshave provided a wealth of functional details that havegreatly enhanced the understanding of the pathologicalmechanisms, it has always been clear that heterologousexpression of the mutant protein bears the intrinsiclimitation of the lack of a proper intracellular environmentand the lack of pathological remodeling. The resultsobtained from the application of the next generationsequencing technique to patients suffering from cardiacdiseases have identified several loci, mostly in non-codingDNA regions, which still await functional analysis. Theisolation and culture of human embryonic stem cells hasinitially provided a constant source of cells from whichcardiomyocytes (CMs) can be obtained by differentiation.Furthermore, the possibility to reprogram cellular fateto a pluripotent state, has opened this process to thestudy of genetic diseases. Thus induced pluripotentstem cells (iPSCs) represent a completely new cellularmodel that overcomes the limitations of heterologousstudies. Importantly, due to the possibility to keepspontaneously beating CMs in culture for several months,during which they show a certain degree of maturation/aging, this approach will also provide a system in whichto address the effect of long-term expression of themutated proteins or any other DNA mutation, in termsof electrophysiological remodeling. Moreover, sinceiPSC preserve the entire patients' genetic context, thesystem will help the physicians in identifying the mostappropriate pharmacological intervention to correct thefunctional alteration. This article summarizes the currentknowledge of cardiac genetic

  11. Quasiperiodicity route to chaos in cardiac conduction model

    Science.gov (United States)

    Quiroz-Juárez, M. A.; Vázquez-Medina, R.; Ryzhii, E.; Ryzhii, M.; Aragón, J. L.

    2017-01-01

    It has been suggested that cardiac arrhythmias are instances of chaos. In particular that the ventricular fibrillation is a form of spatio-temporal chaos that arises from normal rhythm through a quasi-periodicity or Ruelle-Takens-Newhouse route to chaos. In this work, we modify the heterogeneous oscillator model of cardiac conduction system proposed in Ref. [Ryzhii E, Ryzhii M. A heterogeneous coupled oscillator model for simulation of ECG signals. Comput Meth Prog Bio 2014;117(1):40-49. doi:10.1016/j.cmpb.2014.04.009.], by including an ectopic pacemaker that stimulates the ventricular muscle to model arrhythmias. With this modification, the transition from normal rhythm to ventricular fibrillation is controlled by a single parameter. We show that this transition follows the so-called torus of quasi-periodic route to chaos, as verified by using numerical tools such as power spectrum and largest Lyapunov exponent.

  12. Network dynamics of 3D engineered neuronal cultures: a new experimental model for in-vitro electrophysiology.

    Science.gov (United States)

    Frega, Monica; Tedesco, Mariateresa; Massobrio, Paolo; Pesce, Mattia; Martinoia, Sergio

    2014-06-30

    Despite the extensive use of in-vitro models for neuroscientific investigations and notwithstanding the growing field of network electrophysiology, all studies on cultured cells devoted to elucidate neurophysiological mechanisms and computational properties, are based on 2D neuronal networks. These networks are usually grown onto specific rigid substrates (also with embedded electrodes) and lack of most of the constituents of the in-vivo like environment: cell morphology, cell-to-cell interaction and neuritic outgrowth in all directions. Cells in a brain region develop in a 3D space and interact with a complex multi-cellular environment and extracellular matrix. Under this perspective, 3D networks coupled to micro-transducer arrays, represent a new and powerful in-vitro model capable of better emulating in-vivo physiology. In this work, we present a new experimental paradigm constituted by 3D hippocampal networks coupled to Micro-Electrode-Arrays (MEAs) and we show how the features of the recorded network dynamics differ from the corresponding 2D network model. Further development of the proposed 3D in-vitro model by adding embedded functionalized scaffolds might open new prospects for manipulating, stimulating and recording the neuronal activity to elucidate neurophysiological mechanisms and to design bio-hybrid microsystems.

  13. Avaliação eletrofisiológica cardíaca em pacientes com sarcoidose Evaluación electrofisiológica cardíaca en pacientes con sarcoidosis Cardiac electrophysiological assessment in patients with sarcoidosis

    Directory of Open Access Journals (Sweden)

    Jefferson Curimbaba

    2011-04-01

    sospecha de afectación cardíaca. MÉTODOS:Se estudiaron a 22 pacientes con una media de edad de 55,32 ± 13,13 años, con diagnóstico de sarcoidosis y sospecha de afectación cardíaca.Se sometieron a evaluación clínica, exámenes de laboratorio, electrocardiograma, ecocardiograma, Holter de 24 h, centellografía con galio o tecnecio y estudio electrofisiológico. En los casos seleccionados se realizó tomografía por emisión de positrones o la resonancia magnética.Los pacientes fueron seguidos en ambulatorio, en consultas trimestrales. RESULTADOS:La afectación cardíaca se comprobó en cuatro (18,2% pacientes.Extrasístoles ventriculares con densidad > 100/24 h se documentaron en el Holter de 24 h en 12 (54,5 % pacientes.Los estudios electrofisiológicos revelaron un aumento del intervalo HV en siete (31,8% y punto de Wenckebach aumentado en cuatro (18,2% pacientes. No hubo inducción de fibrilación auricular en siete (31,8% y de taquicardia ventricular sostenida en uno (4,5%. En los cuatro pacientes con sarcoidosis cardiaca confirmada, extrasístoles ventriculares (EVs, con densidad > 100/24 h se documentaron en todos, dos presentaban prolongación del intervalo HV y fibrilación auricular se indujo en dos. La taquicardia ventricular sostenida no fue inducida en cualquiera de estos pacientes. Después de un periodo medio de seguimiento de 20,9 ± 15,7 meses, un paciente con sarcoidosis cardíaca tuvo muerte súbita. CONCLUSIÓN: Los pacientes con sarcoidosis y sospecha de afectación cardíaca tienen una alta prevalencia de EVs y trastornos del sistema de conducción.BACKGROUND: Sarcoidosis is a multisystem granulomatous disease of unknown origin that can cause sudden death. OBJECTIVE: Electrophysiological evaluation of patients with suspected sarcoidosis with cardiac involvement. METHODS: We studied 22 patients with mean age of 55.32 ± 13.13 years, diagnosed with sarcoidosis and suspected cardiac involvement. These patients underwent clinical evaluation

  14. Validation of transpulmonary thermodilution cardiac output measurement in a pediatric animal model.

    NARCIS (Netherlands)

    Lemson, J.; Boode, W.P. de; Hopman, J.C.W.; Singh, S.K.; Hoeven, J.G. van der

    2008-01-01

    OBJECTIVE: This study was undertaken to validate the transpulmonary thermodilution cardiac output measurement (CO(TPTD)) in a controlled newborn animal model under various hemodynamic conditions with special emphasis on low cardiac output. DESIGN: Prospective, experimental, pediatric animal study. S

  15. LR-Spring Mass Model for Cardiac Surgical Simulation

    DEFF Research Database (Denmark)

    Mosegaard, Jesper

    2004-01-01

    The purpose of the research conducted was to develop a real-time surgical simulator for preoperative planning of surgery in congenital heart disease. The main problem simulating procedures on cardiac morphology is the need for a large degree of detail and simulation speed. In combination...... with a demand for physically realistic real-time behaviour this gives us tradeoffs not easily balanced. The LR-Spring Mass model handles these constraints by the use of domain specific knowledge....

  16. Microfluidic cardiac cell culture model (μCCCM).

    Science.gov (United States)

    Giridharan, Guruprasad A; Nguyen, Mai-Dung; Estrada, Rosendo; Parichehreh, Vahidreza; Hamid, Tariq; Ismahil, Mohamed Ameen; Prabhu, Sumanth D; Sethu, Palaniappan

    2010-09-15

    Physiological heart development and cardiac function rely on the response of cardiac cells to mechanical stress during hemodynamic loading and unloading. These stresses, especially if sustained, can induce changes in cell structure, contractile function, and gene expression. Current cell culture techniques commonly fail to adequately replicate physical loading observed in the native heart. Therefore, there is a need for physiologically relevant in vitro models that recreate mechanical loading conditions seen in both normal and pathological conditions. To fulfill this need, we have developed a microfluidic cardiac cell culture model (μCCCM) that for the first time allows in vitro hemodynamic stimulation of cardiomyocytes by directly coupling cell structure and function with fluid induced loading. Cells are cultured in a small (1 cm diameter) cell culture chamber on a thin flexible silicone membrane. Integrating the cell culture chamber with a pump, collapsible pulsatile valve and an adjustable resistance element (hemostatic valve) in series allow replication of various loading conditions experienced in the heart. This paper details the design, modeling, fabrication and characterization of fluid flow, pressure and stretch generated at various frequencies to mimic hemodynamic conditions associated with the normal and failing heart. Proof-of-concept studies demonstrate successful culture of an embryonic cardiomyoblast line (H9c2 cells) and establishment of an in vivo like phenotype within this system.

  17. Cardiac magnetic source imaging based on current multipole model

    Institute of Scientific and Technical Information of China (English)

    Tang Fa-Kuan; Wang Qian; Hua Ning; Lu Hong; Tang Xue-Zheng; Ma Ping

    2011-01-01

    It is widely accepted that the heart current source can be reduced into a current multipole. By adopting three linear inverse methods, the cardiac magnetic imaging is achieved in this article based on the current multipole model expanded to the first order terms. This magnetic imaging is realized in a reconstruction plane in the centre of human heart, where the current dipole array is employed to represent realistic cardiac current distribution. The current multipole as testing source generates magnetic fields in the measuring plane, serving as inputs of cardiac magnetic inverse problem. In the heart-torso model constructed by boundary element method, the current multipole magnetic field distribution is compared with that in the homogeneous infinite space, and also with the single current dipole magnetic field distribution.Then the minimum-norm least-squares (MNLS) method, the optimal weighted pseuDOInverse method (OWPIM), and the optimal constrained linear inverse method (OCLIM) are selected as the algorithms for inverse computation based on current multipole model innovatively, and the imaging effects of these three inverse methods are compared. Besides,two reconstructing parameters, residual and mean residual, are also discussed, and their trends under MNLS, OWPIM and OCLIM each as a function of SNR are obtained and compared.

  18. Genetically engineered cardiac pacemaker: Stem cells transfected with HCN2 gene and myocytes-A model

    Energy Technology Data Exchange (ETDEWEB)

    Kanani, S. [Institut Genomique Fonctionelle, 141 Rue de la Cardonille, 34396 Montpellier (France); Institut Non Lineaire de Nice, CNRS and Universite de Nice, 1361 route des Lucioles, 06560 Valbonne (France); Pumir, A. [Institut Non Lineaire de Nice, CNRS and Universite de Nice, 1361 route des Lucioles, 06560 Valbonne (France); Laboratoire J.A. Dieudonne, CNRS and Universite de Nice, Parc Valrose, 06108 Nice (France)], E-mail: alain.pumir@unice.fr; Krinsky, V. [Institut Non Lineaire de Nice, CNRS and Universite de Nice, 1361 route des Lucioles, 06560 Valbonne (France)

    2008-01-07

    One of the successfully tested methods to design genetically engineered cardiac pacemaker cells consists in transfecting a human mesenchymal stem cell (hMSC) with a HCN2 gene and connecting it to a myocyte. We develop and study a mathematical model, describing a myocyte connected to a hMSC transfected with a HCN2 gene. The cardiac action potential is described both with the simple Beeler-Reuter model, as well as with the elaborate dynamic Luo-Rudy model. The HCN2 channel is described by fitting electrophysiological records, in the spirit of Hodgkin-Huxley. The model shows that oscillations can occur in a pair myocyte-stem cell, that was not observed in the experiments yet. The model predicted that: (1) HCN pacemaker channels can induce oscillations only if the number of expressed I{sub K1} channels is low enough. At too high an expression level of I{sub K1} channels, oscillations cannot be induced, no matter how many pacemaker channels are expressed. (2) At low expression levels of I{sub K1} channels, a large domain of values in the parameter space (n, N) exists, where oscillations should be observed. We denote N the number of expressed pacemaker channels in the stem cell, and n the number of gap junction channels coupling the stem cell and the myocyte. (3) The expression levels of I{sub K1} channels observed in ventricular myocytes, both in the Beeler-Reuter and in the dynamic Luo-Rudy models are too high to allow to observe oscillations. With expression levels below {approx}1/4 of the original value, oscillations can be observed. The main consequence of this work is that in order to obtain oscillations in an experiment with a myocyte-stem cell pair, increasing the values of n, N is unlikely to be helpful, unless the expression level of I{sub K1} has been reduced enough. The model also allows us to explore levels of gene expression not yet achieved in experiments, and could be useful to plan new experiments, aimed at improving the robustness of the oscillations.

  19. Genetically engineered cardiac pacemaker: Stem cells transfected with HCN2 gene and myocytes—A model

    Science.gov (United States)

    Kanani, S.; Pumir, A.; Krinsky, V.

    2008-01-01

    One of the successfully tested methods to design genetically engineered cardiac pacemaker cells consists in transfecting a human mesenchymal stem cell (hMSC) with a HCN2 gene and connecting it to a myocyte. We develop and study a mathematical model, describing a myocyte connected to a hMSC transfected with a HCN2 gene. The cardiac action potential is described both with the simple Beeler Reuter model, as well as with the elaborate dynamic Luo Rudy model. The HCN2 channel is described by fitting electrophysiological records, in the spirit of Hodgkin Huxley. The model shows that oscillations can occur in a pair myocyte-stem cell, that was not observed in the experiments yet. The model predicted that: (1) HCN pacemaker channels can induce oscillations only if the number of expressed I channels is low enough. At too high an expression level of I channels, oscillations cannot be induced, no matter how many pacemaker channels are expressed. (2) At low expression levels of I channels, a large domain of values in the parameter space (n, N) exists, where oscillations should be observed. We denote N the number of expressed pacemaker channels in the stem cell, and n the number of gap junction channels coupling the stem cell and the myocyte. (3) The expression levels of I channels observed in ventricular myocytes, both in the Beeler Reuter and in the dynamic Luo Rudy models are too high to allow to observe oscillations. With expression levels below ˜1/4 of the original value, oscillations can be observed. The main consequence of this work is that in order to obtain oscillations in an experiment with a myocyte-stem cell pair, increasing the values of n, N is unlikely to be helpful, unless the expression level of I has been reduced enough. The model also allows us to explore levels of gene expression not yet achieved in experiments, and could be useful to plan new experiments, aimed at improving the robustness of the oscillations.

  20. Subject-specific models for image-guided cardiac surgery

    Science.gov (United States)

    Wierzbicki, Marcin; Moore, John; Drangova, Maria; Peters, Terry

    2008-10-01

    Three-dimensional visualization for planning and guidance is still not routinely available for minimally invasive cardiac surgery (MICS). This can be addressed by providing the surgeon with subject-specific geometric models derived from 3D preoperative images for planning of port locations or to rehearse the procedure. For guidance purposes, these models can also be registered to the subject using intraoperative images. In this paper, we present a method for extracting subject-specific heart geometry from preoperative MR images. The main obstacle we face is the low quality of clinical data in terms of resolution, signal-to-noise ratio, and presence of artefacts. Instead of using these images directly, we approach the problem in three steps: (1) generate a high quality template model, (2) register the template with the preoperative data, and (3) animate the result over the cardiac cycle. Validation of this approach showed that dynamic subject-specific models can be generated with a mean error of 3.6 ± 1.1 mm from low resolution target images (6 mm slices). Thus, the models are sufficiently accurate for MICS training and procedure planning. In terms of guidance, we also demonstrate how the resulting models may be adapted to the operating room using intraoperative ultrasound imaging.

  1. Computational modeling of muscular thin films for cardiac repair

    Science.gov (United States)

    Böl, Markus; Reese, Stefanie; Parker, Kevin Kit; Kuhl, Ellen

    2009-03-01

    Motivated by recent success in growing biohybrid material from engineered tissues on synthetic polymer films, we derive a computational simulation tool for muscular thin films in cardiac repair. In this model, the polydimethylsiloxane base layer is simulated in terms of microscopically motivated tetrahedral elements. Their behavior is characterized through a volumetric contribution and a chain contribution that explicitly accounts for the polymeric microstructure of networks of long chain molecules. Neonatal rat ventricular cardiomyocytes cultured on these polymeric films are modeled with actively contracting truss elements located on top of the sheet. The force stretch response of these trusses is motivated by the cardiomyocyte force generated during active contraction as suggested by the filament sliding theory. In contrast to existing phenomenological models, all material parameters of this novel model have a clear biophyisical interpretation. The predictive features of the model will be demonstrated through the simulation of muscular thin films. First, the set of parameters will be fitted for one particular experiment documented in the literature. This parameter set is then used to validate the model for various different experiments. Last, we give an outlook of how the proposed simulation tool could be used to virtually predict the response of multi-layered muscular thin films. These three-dimensional constructs show a tremendous regenerative potential in repair of damaged cardiac tissue. The ability to understand, tune and optimize their structural response is thus of great interest in cardiovascular tissue engineering.

  2. Atrial Electrophysiological Remodeling and Fibrillation in Heart Failure

    Science.gov (United States)

    Pandit, Sandeep V.; Workman, Antony J.

    2016-01-01

    Heart failure (HF) causes complex, chronic changes in atrial structure and function, which can cause substantial electrophysiological remodeling and predispose the individual to atrial fibrillation (AF). Pharmacological treatments for preventing AF in patients with HF are limited. Improved understanding of the atrial electrical and ionic/molecular mechanisms that promote AF in these patients could lead to the identification of novel therapeutic targets. Animal models of HF have identified numerous changes in atrial ion currents, intracellular calcium handling, action potential waveform and conduction, as well as expression and signaling of associated proteins. These studies have shown that the pattern of electrophysiological remodeling likely depends on the duration of HF, the underlying cardiac pathology, and the species studied. In atrial myocytes and tissues obtained from patients with HF or left ventricular systolic dysfunction, the data on changes in ion currents and action potentials are largely equivocal, probably owing mainly to difficulties in controlling for the confounding influences of multiple variables, such as patient’s age, sex, disease history, and drug treatments, as well as the technical challenges in obtaining such data. In this review, we provide a summary and comparison of the main animal and human electrophysiological studies to date, with the aim of highlighting the consistencies in some of the remodeling patterns, as well as identifying areas of contention and gaps in the knowledge, which warrant further investigation. PMID:27812293

  3. Arrhythmogenesis in the heart: Multiscale modeling of the effects of defibrillation shocks and the role of electrophysiological heterogeneity

    Science.gov (United States)

    Arevalo, Hermenegild; Rodriguez, Blanca; Trayanova, Natalia

    2007-03-01

    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.

  4. Dose-Escalation Study for Cardiac Radiosurgery in a Porcine Model

    Energy Technology Data Exchange (ETDEWEB)

    Blanck, Oliver, E-mail: oliver.blanck@uksh.de [Department of Radiation Oncology, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck (Germany); CyberKnife Center Northern Germany, Guestrow (Germany); Bode, Frank [Medical Department II, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck (Germany); Gebhard, Maximilian [Institute of Pathology, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck (Germany); Hunold, Peter [Department of Radiology and Nuclear Medicine, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck (Germany); Brandt, Sebastian [Department of Anaesthesiology and Intensive Care Medicine, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck (Germany); Bruder, Ralf [Institute for Robotics and Cognitive Systems, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck (Germany); Grossherr, Martin [Department of Anaesthesiology and Intensive Care Medicine, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck (Germany); Vonthein, Reinhard [Institute of Medical Biometry and Statistics, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck (Germany); Rades, Dirk [Department of Radiation Oncology, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck (Germany); Dunst, Juergen [Department of Radiation Oncology, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck (Germany); University Copenhagen (Denmark)

    2014-07-01

    Purpose: To perform a proof-of-principle dose-escalation study to radiosurgically induce scarring in cardiac muscle tissue to block veno-atrial electrical connections at the pulmonary vein antrum, similar to catheter ablation. Methods and Materials: Nine mini-pigs underwent pretreatment magnetic resonance imaging (MRI) evaluation of heart function and electrophysiology assessment by catheter measurements in the right superior pulmonary vein (RSPV). Immediately after examination, radiosurgery with randomized single-fraction doses of 0 and 17.5-35 Gy in 2.5-Gy steps were delivered to the RSPV antrum (target volume 5-8 cm{sup 3}). MRI and electrophysiology were repeated 6 months after therapy, followed by histopathologic examination. Results: Transmural scarring of cardiac muscle tissue was noted with doses ≥32.5 Gy. However, complete circumferential scarring of the RSPV was not achieved. Logistic regressions showed that extent and intensity of fibrosis significantly increased with dose. The 50% effective dose for intense fibrosis was 31.3 Gy (odds ratio 2.47/Gy, P<.01). Heart function was not affected, as verified by MRI and electrocardiogram evaluation. Adjacent critical structures were not damaged, as verified by pathology, demonstrating the short-term safety of small-volume cardiac radiosurgery with doses up to 35 Gy. Conclusions: Radiosurgery with doses >32.5 Gy in the healthy pig heart can induce circumscribed scars at the RSPV antrum noninvasively, mimicking the effect of catheter ablation. In our study we established a significant dose-response relationship for cardiac radiosurgery. The long-term effects and toxicity of such high radiation doses need further investigation in the pursuit of cardiac radiosurgery for noninvasive treatment of atrial fibrillation.

  5. Forward and Inverse Modelling Approaches for Prediction of Light Stimulus from Electrophysiological Response in Plants

    CERN Document Server

    Chatterjee, Shre Kumar; Das, Saptarshi; Manzella, Veronica; Vitaletti, Andrea; Masi, Elisa; Santopolo, Luisa; Mancuso, Stefano; Maharatna, Koushik

    2014-01-01

    In this paper, system identification approach has been adopted to develop a novel dynamical model for describing the relationship between light as an environmental stimulus and the electrical response as the measured output for a bay leaf (Laurus nobilis) plant. More specifically, the target is to predict the characteristics of the input light stimulus (in terms of on-off timing, duration and intensity) from the measured electrical response - leading to an inverse problem. We explored two major classes of system estimators to develop dynamical models - linear and nonlinear - and their several variants for establishing a forward and also an inverse relationship between the light stimulus and plant electrical response. The best class of models are given by the Nonlinear Hammerstein-Wiener (NLHW) estimator showing good data fitting results over other linear and nonlinear estimators in a statistical sense. Consequently, a few set of models using different functional variants of NLHW has been developed and their a...

  6. Designs that make a difference: the Cardiac Universal Bed model.

    Science.gov (United States)

    Johnson, Jackie; Brown, Katherine Kay; Neal, Kelly

    2003-01-01

    Information contained in this article includes some of the findings from a joint research project conducted by Corazon Consulting and Ohio State University Medical Center on national trends in Cardiac Universal Bed (CUB) utilization. This article outlines current findings and "best practice" standards related to the benefits of developing care delivery models to differentiate an organization with a competitive advantage in the highly dynamic marketplace of cardiovascular care. (OSUMC, a Corazon client, is incorporating the CUB into their Ross Heart Hospital slated to open this spring.)

  7. In vivo models of cardiac diseases: application to drug development and screening.

    Science.gov (United States)

    Rokutan, Hirofumi; Anker, Stefan D; Springer, Jochen

    2010-01-01

    Cardiac disease is the top cause of human mortality in the Western world. Current drug therapy for cardiac disease has been established via experimental studies using a variety of in vivo animal models. The purpose of this review is to discuss the features (advantages and limitations) of the mainly used in vivo models of cardiac disease and provide the reader with an overview of how they can be utilized in the development and screening of cardiac drugs. A search for articles focusing on and including in vivo models for the main areas of cardiac diseases was performed on PubMed. We also searched the reference lists of identified articles for further original articles. Large and small animal models including genetically modified ones have made accomplishments in the process of cardiac drug development with different clinical relevance. However, there is still a clear need for lessening the gap between human and experimental models by improving in vivo models.

  8. Cardiac CT for planning redo cardiac surgery: effect of knowledge-based iterative model reconstruction on image quality

    Energy Technology Data Exchange (ETDEWEB)

    Oda, Seitaro [MedStar Washington Hospital Center, Department of Cardiology, Washington, DC (United States); Kumamoto University, Department of Diagnostic Radiology, Faculty of Life Sciences, Kumamoto (Japan); Weissman, Gaby; Weigold, W. Guy [MedStar Washington Hospital Center, Department of Cardiology, Washington, DC (United States); Vembar, Mani [Philips Healthcare, CT Clinical Science, Cleveland, OH (United States)

    2015-01-15

    The purpose of this study was to investigate the effects of knowledge-based iterative model reconstruction (IMR) on image quality in cardiac CT performed for the planning of redo cardiac surgery by comparing IMR images with images reconstructed with filtered back-projection (FBP) and hybrid iterative reconstruction (HIR). We studied 31 patients (23 men, 8 women; mean age 65.1 ± 16.5 years) referred for redo cardiac surgery who underwent cardiac CT. Paired image sets were created using three types of reconstruction: FBP, HIR, and IMR. Quantitative parameters including CT attenuation, image noise, and contrast-to-noise ratio (CNR) of each cardiovascular structure were calculated. The visual image quality - graininess, streak artefact, margin sharpness of each cardiovascular structure, and overall image quality - was scored on a five-point scale. The mean image noise of FBP, HIR, and IMR images was 58.3 ± 26.7, 36.0 ± 12.5, and 14.2 ± 5.5 HU, respectively; there were significant differences in all comparison combinations among the three methods. The CNR of IMR images was better than that of FBP and HIR images in all evaluated structures. The visual scores were significantly higher for IMR than for the other images in all evaluated parameters. IMR can provide significantly improved qualitative and quantitative image quality at in cardiac CT for planning of reoperative cardiac surgery. (orig.)

  9. Differences in electrophysiological properties of functionally identified nociceptive sensory neurons in an animal model of cancer-induced bone pain

    Science.gov (United States)

    Zhu, Yong Fang; Ungard, Robert; Seidlitz, Eric; Zacal, Natalie; Huizinga, Jan; Henry, James L

    2016-01-01

    Background Bone cancer pain is often severe, yet little is known about mechanisms generating this type of chronic pain. While previous studies have identified functional alterations in peripheral sensory neurons that correlate with bone tumours, none has provided direct evidence correlating behavioural nociceptive responses with properties of sensory neurons in an intact bone cancer model. Results In a rat model of prostate cancer-induced bone pain, we confirmed tactile hypersensitivity using the von Frey test. Subsequently, we recorded intracellularly from dorsal root ganglion neurons in vivo in anesthetized animals. Neurons remained connected to their peripheral receptive terminals and were classified on the basis of action potential properties, responses to dorsal root stimulation, and to mechanical stimulation of the respective peripheral receptive fields. Neurons included C-, Aδ-, and Aβ-fibre nociceptors, identified by their expression of substance P. We suggest that bone tumour may induce phenotypic changes in peripheral nociceptors and that these could contribute to bone cancer pain. Conclusions This work represents a significant technical and conceptual advance in the study of peripheral nociceptor functions in the development of cancer-induced bone pain. This is the first study to report that changes in sensitivity and excitability of dorsal root ganglion primary afferents directly correspond to mechanical allodynia and hyperalgesia behaviours following prostate cancer cell injection into the femur of rats. Furthermore, our unique combination of techniques has allowed us to follow, in a single neuron, mechanical pain-related behaviours, electrophysiological changes in action potential properties, and dorsal root substance P expression. These data provide a more complete understanding of this unique pain state at the cellular level that may allow for future development of mechanism-based treatments for cancer-induced bone pain. PMID:27030711

  10. Anti-epileptogenesis: Electrophysiology, diffusion tensor imaging and behavior in a genetic absence model

    NARCIS (Netherlands)

    Luijtelaar, E.L.J.M. van; Mishra, A.M.; Edelbroek, P.M.; Coman, D.; Frankenmolen, N.L.; Schaapsmeerders, P.; Covolato, G.; Danielson, N.; Niermann, H.C.M.; Janeczko, K.; Kiemeneij, A.; Burinov, J.; Bashyal, C.; Coquillette, M.; Luttjohann, A.K.; Hyder, F.; Blumenfeld, H.; Rijn, C.M. van

    2013-01-01

    The beneficial effects of chronic and early pharmacological treatment with ethosuximide on epileptogenesis were studied in a genetic absence epilepsy model comorbid for depression. It was also investigated whether there is a critical treatment period and treatment length. Cortical excitability in th

  11. A model of working memory: bridging the gap between electrophysiology and human brain imaging.

    Science.gov (United States)

    Tagamets, M A; Horwitz, B

    2000-01-01

    Human neuroimaging methods such as positron emission tomography and functional magnetic resonance imaging have made possible the study of large-scale distributed networks in the behaving human brain. Although many imaging studies support and extend knowledge gained from other experimental modalities such as animal single-cell recordings, there have also been a substantial number of experiments that appear to contradict the animal studies. Part of the reason for this is that neuroimaging is an indirect measure of neuronal firing activity, and thus interpretation is difficult. Computational modeling can help to bridge the gap by providing a substrate for making explicit the assumptions and constraints provided from other sources such as anatomy, physiology and behavior. We describe a large-scale model of working memory that we have used to examine a number of issues relating to the interpretation of imaging data. The gating mechanism that regulates engagement and retention of short-term memory is revised to better reflect hypothesized underlying neuromodulatory mechanisms. It is shown that in addition to imparting better performance for the memory circuit, this mechanism also provides a better match to imaging data from working memory studies.

  12. Electrophysiological Evidence for a Sensory Recruitment Model of Somatosensory Working Memory.

    Science.gov (United States)

    Katus, Tobias; Grubert, Anna; Eimer, Martin

    2015-12-01

    Sensory recruitment models of working memory assume that information storage is mediated by the same cortical areas that are responsible for the perceptual processing of sensory signals. To test this assumption, we measured somatosensory event-related brain potentials (ERPs) during a tactile delayed match-to-sample task. Participants memorized a tactile sample set at one task-relevant hand to compare it with a subsequent test set on the same hand. During the retention period, a sustained negativity (tactile contralateral delay activity, tCDA) was elicited over primary somatosensory cortex contralateral to the relevant hand. The amplitude of this component increased with memory load and was sensitive to individual limitations in memory capacity, suggesting that the tCDA reflects the maintenance of tactile information in somatosensory working memory. The tCDA was preceded by a transient negativity (N2cc component) with a similar contralateral scalp distribution, which is likely to reflect selection of task-relevant tactile stimuli at the encoding stage. The temporal sequence of N2cc and tCDA components mirrors previous observations from ERP studies of working memory in vision. The finding that the sustained somatosensory delay period activity varies as a function of memory load supports a sensory recruitment model for spatial working memory in touch.

  13. Palmitoylethanolamide Reduces Neuropsychiatric Behaviors by Restoring Cortical Electrophysiological Activity in a Mouse Model of Mild Traumatic Brain Injury

    Science.gov (United States)

    Guida, Francesca; Boccella, Serena; Iannotta, Monica; De Gregorio, Danilo; Giordano, Catia; Belardo, Carmela; Romano, Rosaria; Palazzo, Enza; Scafuro, Maria A.; Serra, Nicola; de Novellis, Vito; Rossi, Francesco; Maione, Sabatino; Luongo, Livio

    2017-01-01

    Traumatic brain injury (TBI) represents a major public health problem, which is associated with neurological dysfunction. In severe or moderate cases of TBI, in addition to its high mortality rate, subjects may encounter diverse behavioral dysfunctions. Previous reports suggest that an association between TBI and chronic pain syndromes tends to be more common in patients with mild forms of brain injury. Despite causing minimal brain damage, mild TBI (mTBI) often leads to persistent psychologically debilitating symptoms, which can include anxiety, various forms of memory and learning deficits, and depression. At present, no effective treatment options are available for these symptoms, and little is known about the complex cellular activity affecting neuronal activity that occurs in response to TBI during its late phase. Here, we used a mouse model to investigate the effect of Palmitoylethanolamide (PEA) on both the sensorial and neuropsychiatric dysfunctions associated with mTBI through behavioral, electrophysiological, and biomolecular approaches. Fourteen-day mTBI mice developed anxious, aggressive, and reckless behavior, whilst depressive-like behavior and impaired social interactions were observed from the 60th day onward. Altered behavior was associated with changes in interleukin 1 beta (IL-1β) expression levels and neuronal firing activity in the medial prefrontal cortex. Compared with vehicle, PEA restored the behavioral phenotype and partially normalized the biochemical and functional changes occurring at the supraspinal level. In conclusion, our findings reveal some of the supraspinal modifications responsible for the behavioral alterations associated with mTBI and suggest PEA as a pharmacological tool to ameliorate neurological dysfunction induced by the trauma. PMID:28321191

  14. Mouse models for the study of postnatal cardiac hypertrophy

    Directory of Open Access Journals (Sweden)

    A. Del Olmo-Turrubiarte

    2015-06-01

    Full Text Available The main objective of this study was to create a postnatal model for cardiac hypertrophy (CH, in order to explain the mechanisms that are present in childhood cardiac hypertrophy. Five days after implantation, intraperitoneal (IP isoproterenol (ISO was injected for 7 days to pregnant female mice. The fetuses were obtained at 15, 17 and 19 dpc from both groups, also newborns (NB, neonates (7–15 days and young adults (6 weeks of age. Histopathological exams were done on the hearts. Immunohistochemistry and western blot demonstrated GATA4 and PCNA protein expression, qPCR real time the mRNA of adrenergic receptors (α-AR and β-AR, alpha and beta myosins (α-MHC, β-MHC and GATA4. After the administration of ISO, there was no change in the number of offsprings. We observed significant structural changes in the size of the offspring hearts. Morphometric analysis revealed an increase in the size of the left ventricular wall and interventricular septum (IVS. Histopathological analysis demonstrated loss of cellular compaction and presence of left ventricular small fibrous foci after birth. Adrenergic receptors might be responsible for changing a physiological into a pathological hypertrophy. However GATA4 seemed to be the determining factor in the pathology. A new animal model was established for the study of pathologic CH in early postnatal stages.

  15. Long-term fish oil supplementation induces cardiac electrical remodeling by changing channel protein expression in the rabbit model.

    Directory of Open Access Journals (Sweden)

    Xulin Xu

    Full Text Available Clinical trials and epidemiological studies have suggested that dietary fish oil (FO supplementation can provide an anti-arrhythmic benefit in some patient populations. The underlying mechanisms are not entirely clear. We wanted to understand how FO supplementation (for 4 weeks affected the action potential configuration/duration of ventricular myocytes, and the ionic mechanism(s/molecular basis for these effects. The experiments were conducted on adult rabbits, a widely used animal model for cardiac electrophysiology and pathophysiology. We used gas chromatography-mass spectroscopy to confirm that FO feeding produced a marked increase in the content of n-3 polyunsaturated fatty acids in the phospholipids of rabbit hearts. Left ventricular myocytes were used in current and voltage clamp experiments to monitor action potentials and ionic currents, respectively. Action potentials of myocytes from FO-fed rabbits exhibited much more positive plateau voltages and prolonged durations. These changes could be explained by an increase in the L-type Ca current (I(CaL and a decrease in the transient outward current (I(to in these myocytes. FO feeding did not change the delayed rectifier or inward rectifier current. Immunoblot experiments showed that the FO-feeding induced changes in I(CaL and I(to were associated with corresponding changes in the protein levels of major pore-forming subunits of these channels: increase in Cav1.2 and decrease in Kv4.2 and Kv1.4. There was no change in other channel subunits (Cav1.1, Kv4.3, KChIP2, and ERG1. We conclude that long-term fish oil supplementation can impact on cardiac electrical activity at least partially by changing channel subunit expression in cardiac myocytes.

  16. Comparison of the Frequency-dependent Effects of Amiodarone on Ventricular Electrophysiology in Congestive Heart Failure Canine Models and Normal Dogs

    Institute of Scientific and Technical Information of China (English)

    Zhou Shuxian; Zhang Yuling; Lei Juan; Wu Wei; Zhang Xuming

    2007-01-01

    Objectives To compare the frequency-dependent effects of amiodarone (Ami) on ventricular electrophysiology in right ventricular rapid pacing-induced congestive heart failure (CHF) canine models.Methods Thirty-two dogs were randomized into four groups: the control group, the Ami group in which the normal dogs were given Ami orally 300 mg a day for 4~5 weeks, the CHF group induced by right ventricular rapid pacing ( 240 pulses. min -1 for 4 ~ 5 weeks), and the group of CHF dogs fed with Ami orally 300 mg a day for 4 ~ 5 weeks. The techniques of electrical stimulation and monophasic action potential (MAP) recording were used in the electrophysiology studies. Results The effects of Ami on ventricular MAP duration(MAPD90) and effective refractory period (VERP)were not frequency-dependent in CHF dogs. There was also no frequency-dependent effect on the increase in the ratio of VERP to MAPD90 (VERP/MAPD90). The prolongation of ventricular conduction time was frequencydependent. Conclusions The frequency-dependent effects of Ami on ventricular electrophysiology in CHF dogs were similar to that in normal dogs.

  17. Anti-epileptogenesis: Electrophysiology, diffusion tensor imaging and behavior in a genetic absence model.

    Science.gov (United States)

    van Luijtelaar, Gilles; Mishra, Asht M; Edelbroek, Peter; Coman, Daniel; Frankenmolen, Nikita; Schaapsmeerders, Pauline; Covolato, Giulio; Danielson, Nathan; Niermann, Hannah; Janeczko, Kryzstof; Kiemeneij, Anne; Burinov, Julija; Bashyal, Chhitij; Coquillette, Madeline; Lüttjohann, Annika; Hyder, Fahmeed; Blumenfeld, Hal; van Rijn, Clementina M

    2013-12-01

    The beneficial effects of chronic and early pharmacological treatment with ethosuximide on epileptogenesis were studied in a genetic absence epilepsy model comorbid for depression. It was also investigated whether there is a critical treatment period and treatment length. Cortical excitability in the form of electrical evoked potentials, but also to cortico-thalamo-cortical network activity (spike-wave discharges, SWD and afterdischarges), white matter changes representing extra cortico-thalamic functions and depressive-like behavior were investigated. WAG/Rij rats received either ethosuximide for 2 months (post natal months 2-3 or 4-5), or ethosuximide for 4 months (2-5) in their drinking water, while control rats drank plain water. EEG measurements were made during treatment, and 6 days and 2 months post treatment. Behavioral test were also done 6 days post treatment. DTI was performed ex vivo post treatment. SWD were suppressed during treatment, and 6 days and 2 months post treatment in the 4 month treated group, as well as the duration of AD elicited by cortical electrical stimulation 6 days post treatment. Increased fractional anisotropy in corpus callosum and internal capsula on DTI was found, an increased P8 evoked potential amplitude and a decreased immobility in the forced swim test. Shorter treatments with ETX had no large effects on any parameter. Chronic ETX has widespread effects not only within but also outside the circuitry in which SWD are initiated and generated, including preventing epileptogenesis and reducing depressive-like symptoms. The treatment of patients before symptom onset might prevent many of the adverse consequences of chronic epilepsy.

  18. A viscoplastic model for the active component in cardiac muscle.

    Science.gov (United States)

    Rubin, M B

    2016-08-01

    The HMK model (Hunter et al. in Prog Biophys Mol Biol 69:289-331, 1998) proposes mechanobiological equations for the influence of intracellular calcium concentration [Formula: see text] on the evolution of bound calcium concentration [Formula: see text] and the tropomyosin kinetics parameter z, which model processes in the active component of the tension in cardiac muscle. The inelastic response due to actin-myosin crossbridge kinetics is modeled in the HMK model with a function Q that depends on the history of the rate of total stretch of the muscle fiber. Here, an alternative model is proposed which models the active component of the muscle fiber as a viscoplastic material. In particular, an evolution equation is proposed for the elastic stretch [Formula: see text] in the active component. Specific forms of the constitutive equations are proposed and used to match experimental data. The proposed viscoplastic formulation allows for separate modeling of three processes: the high rate deactivation of crossbridges causing rapid reduction in active tension; the high but lower rate reactivation of crossbridges causing recovery of active tension; and the low rate relaxation effects characterizing the Hill model of muscles.

  19. Uncertainty Visualization in Forward and Inverse Cardiac Models.

    Science.gov (United States)

    Burton, Brett M; Erem, Burak; Potter, Kristin; Rosen, Paul; Johnson, Chris R; Brooks, Dana H; Macleod, Rob S

    2013-01-01

    Quantification and visualization of uncertainty in cardiac forward and inverse problems with complex geometries is subject to various challenges. Specific to visualization is the observation that occlusion and clutter obscure important regions of interest, making visual assessment difficult. In order to overcome these limitations in uncertainty visualization, we have developed and implemented a collection of novel approaches. To highlight the utility of these techniques, we evaluated the uncertainty associated with two examples of modeling myocardial activity. In one case we studied cardiac potentials during the repolarization phase as a function of variability in tissue conductivities of the ischemic heart (forward case). In a second case, we evaluated uncertainty in reconstructed activation times on the epicardium resulting from variation in the control parameter of Tikhonov regularization (inverse case). To overcome difficulties associated with uncertainty visualization, we implemented linked-view windows and interactive animation to the two respective cases. Through dimensionality reduction and superimposed mean and standard deviation measures over time, we were able to display key features in large ensembles of data and highlight regions of interest where larger uncertainties exist.

  20. Two models of anisotropic propagation of a cardiac excitation wave

    Science.gov (United States)

    Erofeev, I. S.; Agladze, K. I.

    2014-11-01

    Propagation of the action potential in the real heart is direction-dependent (anisotropic). We propose two general physical models explaining this anisotropy on the cellular level. The first, "delay" model takes into account the frequency of the cell-cell transitions in different directions of propagation, assuming each transition requires some small time interval. The second model relies on the assumption that the action potential transmits to the next cell only from the area at the pole of the previous cell. We estimated parameters of both models by doing optical mapping and fluorescent staining of cardiac cell samples grown on polymer fiber substrate. Both models gave reasonable estimations, but predicted different behaviors of the anisotropy ratio (ratio of the highest and lowest wave velocities) after addition of the suppressor of sodium channels such as lidocaine. The results of the experiment on lidocaine effect on anisotropy ratio were in favor of the first, "delay" model. Estimated average cell-cell transition delay was 240 ± 80 μs, which is close to the characteristic values of synaptic delay.

  1. Trigeminal Electrophysiology: a 2 × 2 matrix model for differential diagnosis between temporomandibular disorders and orofacial pain

    OpenAIRE

    Chessa Giacomo; Frisardi Gianni; Sau Gianfranco; Frisardi Flavio

    2010-01-01

    Background Pain due to temporomandibular disorders (TMDs) often has the same clinical symptoms and signs as other types of orofacial pain (OP). The possible presence of serious neurological and/or systemic organic pathologies makes differential diagnosis difficult, especially in early disease stages. In the present study, we performed a qualitative and quantitative electrophysiological evaluation of the neuromuscular responses of the trigeminal nervous system. Using the jaw jerk reflex (JJ...

  2. Time series analysis as input for clinical predictive modeling: Modeling cardiac arrest in a pediatric ICU

    Directory of Open Access Journals (Sweden)

    Kennedy Curtis E

    2011-10-01

    Full Text Available Abstract Background Thousands of children experience cardiac arrest events every year in pediatric intensive care units. Most of these children die. Cardiac arrest prediction tools are used as part of medical emergency team evaluations to identify patients in standard hospital beds that are at high risk for cardiac arrest. There are no models to predict cardiac arrest in pediatric intensive care units though, where the risk of an arrest is 10 times higher than for standard hospital beds. Current tools are based on a multivariable approach that does not characterize deterioration, which often precedes cardiac arrests. Characterizing deterioration requires a time series approach. The purpose of this study is to propose a method that will allow for time series data to be used in clinical prediction models. Successful implementation of these methods has the potential to bring arrest prediction to the pediatric intensive care environment, possibly allowing for interventions that can save lives and prevent disabilities. Methods We reviewed prediction models from nonclinical domains that employ time series data, and identified the steps that are necessary for building predictive models using time series clinical data. We illustrate the method by applying it to the specific case of building a predictive model for cardiac arrest in a pediatric intensive care unit. Results Time course analysis studies from genomic analysis provided a modeling template that was compatible with the steps required to develop a model from clinical time series data. The steps include: 1 selecting candidate variables; 2 specifying measurement parameters; 3 defining data format; 4 defining time window duration and resolution; 5 calculating latent variables for candidate variables not directly measured; 6 calculating time series features as latent variables; 7 creating data subsets to measure model performance effects attributable to various classes of candidate variables; 8

  3. Generation of electrophysiologically functional cardiomyocytes from mouse induced pluripotent stem cells

    Directory of Open Access Journals (Sweden)

    Hongran Wang

    2016-03-01

    Full Text Available Induced pluripotent stem (iPS cells can efficiently differentiate into the three germ layers similar to those formed by differentiated embryonic stem (ES cells. This provides a new source of cells in which to establish preclinical allogeneic transplantation models. Our iPS cells were generated from mouse embryonic fibroblasts (MEFs transfected with the Yamanaka factors, the four transcription factors (Oct4, Sox2, Klf4 and c-Myc, without antibiotic selection or MEF feeders. After the formation of embryoid bodies (EBs, iPS cells spontaneously differentiated into Flk1-positive cardiac progenitors and cardiomyocytes expressing cardiac-specific markers such as alpha sarcomeric actinin (α-actinin, cardiac alpha myosin heavy chain (α-MHC, cardiac troponin T (cTnT, and connexin 43 (CX43, as well as cardiac transcription factors Nk2 homebox 5 (Nkx2.5 and gata binding protein 4 (gata4. The electrophysiological activity of iPS cell-derived cardiomyocytes (iPS-CMs was detected in beating cell clusters with optical mapping and RH237 a voltage-sensitive dye, and in single contracting cells with patch-clamp technology. Incompletely differentiated iPS cells formed teratomas when transplanted into a severe combined immunodeficiency (SCID mouse model of myocardial infarction. Our results show that somatic cells can be reprogrammed into pluripotent stem cells, which in turn spontaneously differentiate into electrophysiologically functional mature cardiomyocytes expressing cardiac-specific makers, and that these cells can potentially be used to repair myocardial infarction (MI in the future.

  4. Recreating the Cardiac Microenvironment in Pluripotent Stem Cell Models of Human Physiology and Disease.

    Science.gov (United States)

    Atmanli, Ayhan; Domian, Ibrahim John

    2016-12-19

    The advent of human pluripotent stem cell (hPSC) biology has opened unprecedented opportunities for the use of tissue engineering to generate human cardiac tissue for in vitro study. Engineering cardiac constructs that recapitulate human development and disease requires faithful recreation of the cardiac niche in vitro. Here we discuss recent progress in translating the in vivo cardiac microenvironment into PSC models of the human heart. We review three key physiologic features required to recreate the cardiac niche and facilitate normal cardiac differentiation and maturation: the biochemical, biophysical, and bioelectrical signaling cues. Finally, we discuss key barriers that must be overcome to fulfill the promise of stem cell biology in preclinical applications and ultimately in clinical practice.

  5. Electrophysiological measures of familiarity memory.

    Science.gov (United States)

    Mecklinger, Axel

    2006-10-01

    Event-related potentials are a valuable tool for the study of human memory function. This selective review provides a brief introduction in models of recognition memory and then describes how ERPs can be used to investigate familiarity memory, an acontextual form of remembering that can be distinguished from the recollection of detailed information of prior events. ERP studies on the mid-frontal old/new effect, the putative electrophysiological correlate of familiarity memory are reviewed. It will be illustrated how familiarity memory is reflected in this effect, how it can electrophysiologically be dissociated from other forms of memory and which brain systems mediate this form of remembering. Recent studies will be reviewed that illustrate that familiarity is not only restricted to single items but can also support the retrieval of associative information.

  6. Acupuncture Effects on Cardiac Functions Measured by Cardiac Magnetic Resonance Imaging in a Feline Model

    Directory of Open Access Journals (Sweden)

    Jen-Hsou Lin

    2010-01-01

    Full Text Available The usefulness of acupuncture (AP as a complementary and/or alternative therapy in animals is well established but more research is needed on its clinical efficacy relative to conventional therapy, and on the underlying mechanisms of the effects of AP. Cardiac magnetic resonance imaging (CMRI, an important tool in monitoring cardiovascular diseases, provides a reliable method to monitor the effects of AP on the cardiovascular system. This controlled experiment monitored the effect electro-acupuncture (EA at bilateral acupoint Neiguan (PC6 on recovery time after ketamine/xylazine cocktail anesthesia in healthy cats. The CMRI data established the basic feline cardiac function index (CFI, including cardiac output and major vessel velocity. To evaluate the effect of EA on the functions of the autonomic nervous and cardiovascular systems, heart rate, respiration rate, electrocardiogram and pulse rate were also measured. Ketamine/xylazine cocktail anesthesia caused a transient hypertension in the cats; EA inhibited this anesthetic-induced hypertension and shortened the post-anesthesia recovery time. Our data support existing knowledge on the cardiovascular benefits of EA at PC6, and also provide strong evidence for the combination of anesthesia and EA to shorten post-anesthesia recovery time and counter the negative effects of anesthetics on cardiac physiology.

  7. Prediction for Major Adverse Outcomes in Cardiac Surgery: Comparison of Three Prediction Models

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    Cheng-Hung Hsieh

    2007-09-01

    Conclusion: The Parsonnet score performed as well as the logistic regression models in predicting major adverse outcomes. The Parsonnet score appears to be a very suitable model for clinicians to use in risk stratification of cardiac surgery.

  8. Petascale computation performance of lightweight multiscale cardiac models using hybrid programming models.

    Science.gov (United States)

    Pope, Bernard J; Fitch, Blake G; Pitman, Michael C; Rice, John J; Reumann, Matthias

    2011-01-01

    Future multiscale and multiphysics models must use the power of high performance computing (HPC) systems to enable research into human disease, translational medical science, and treatment. Previously we showed that computationally efficient multiscale models will require the use of sophisticated hybrid programming models, mixing distributed message passing processes (e.g. the message passing interface (MPI)) with multithreading (e.g. OpenMP, POSIX pthreads). The objective of this work is to compare the performance of such hybrid programming models when applied to the simulation of a lightweight multiscale cardiac model. Our results show that the hybrid models do not perform favourably when compared to an implementation using only MPI which is in contrast to our results using complex physiological models. Thus, with regards to lightweight multiscale cardiac models, the user may not need to increase programming complexity by using a hybrid programming approach. However, considering that model complexity will increase as well as the HPC system size in both node count and number of cores per node, it is still foreseeable that we will achieve faster than real time multiscale cardiac simulations on these systems using hybrid programming models.

  9. Quadratic adaptive algorithm for solving cardiac action potential models.

    Science.gov (United States)

    Chen, Min-Hung; Chen, Po-Yuan; Luo, Ching-Hsing

    2016-10-01

    An adaptive integration method is proposed for computing cardiac action potential models accurately and efficiently. Time steps are adaptively chosen by solving a quadratic formula involving the first and second derivatives of the membrane action potential. To improve the numerical accuracy, we devise an extremum-locator (el) function to predict the local extremum when approaching the peak amplitude of the action potential. In addition, the time step restriction (tsr) technique is designed to limit the increase in time steps, and thus prevent the membrane potential from changing abruptly. The performance of the proposed method is tested using the Luo-Rudy phase 1 (LR1), dynamic (LR2), and human O'Hara-Rudy dynamic (ORd) ventricular action potential models, and the Courtemanche atrial model incorporating a Markov sodium channel model. Numerical experiments demonstrate that the action potential generated using the proposed method is more accurate than that using the traditional Hybrid method, especially near the peak region. The traditional Hybrid method may choose large time steps near to the peak region, and sometimes causes the action potential to become distorted. In contrast, the proposed new method chooses very fine time steps in the peak region, but large time steps in the smooth region, and the profiles are smoother and closer to the reference solution. In the test on the stiff Markov ionic channel model, the Hybrid blows up if the allowable time step is set to be greater than 0.1ms. In contrast, our method can adjust the time step size automatically, and is stable. Overall, the proposed method is more accurate than and as efficient as the traditional Hybrid method, especially for the human ORd model. The proposed method shows improvement for action potentials with a non-smooth morphology, and it needs further investigation to determine whether the method is helpful during propagation of the action potential. Copyright © 2016 Elsevier Ltd. All rights

  10. Electrophysiologic Study of Exhaustive Exercise

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    MA Babaee Bigi

    2010-12-01

    Full Text Available Background: Exhaustive exercise is well known to pose a variety ofhealth hazards, such as sudden cardiac death reported in ultra-marathon runners.Depressed parasympathetic tone is associated with increased risk of suddencardiac death, thus parasympathetic withdrawal in post-exercise phase may be ahigh risk period for sudden death. To date, the effect on cardiacelectrophysiology after exhaustive strenuous exercise has not been described.The aim of this study was to evaluate the impact of severe exhaustive exerciseon cardiac electrophysiology.Methods: The subjects in ranger training were invited to participatein this prospective study. The parameters measured consisted of PR interval, QRSduration, and macro T wave alternans as well as corrected QT, QTc dispersion,Tpeak –Tend interval and Tpeak –Tend dispersion.Results: The study group consisted of 40 consecutive male rangers whocompleted training and the control group (22 healthy age and height matched malesubjects. In regard to electrocardiographic criteria, no differences were foundbetween rangers before and after training program. In respect of therepolarization markers, there were no significant differences between therangers before and after training program.

  11. Electrophysiological characteristics of the athlete's heart

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    Popović Dejana

    2007-01-01

    Full Text Available Introduction. The athletic heart syndrome is characterized by morphological, functional and electrophysiological alterations as an adaptive response to vigorous physical activity. Athletes heart is predominantly associated with a programmed, intensive training. But as there are different kinds of physical activities, the degree of these changes is highly variable. Electrophysiological characteristics of the athlete's heart. The response of the body to vigorous physical activity is a multiorgan system phenomenon. The integrated functioning of each of these organ systems is very important, but the cardiovascular system plays a critical role in mediating the activity. Because of that, most changes in the neurohumoral regulation pre- dominantly affect the cardiovascular system. These changes include: depression of sympathetic activity and stimulation of parasympathetic activity, so electrophysiological characteristics of the athlete's heart must differ from the sedentary. Although these facts, are well known, the athlete's heart is not a precisely defined concept. It is a gray zone between physiology and pathology. Conclusion. Considering the number of sudden cardiac deaths in athletes, it is needless to say how important it is to distinguish physiological changes of the heart due to physical activity, and pathological changes due to some cardiac diseases.

  12. Cardiac lymphatic dynamics after ischemia and reperfusion - experimental model

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    Santos, A.C. E-mail: cristina@imagem.ibili.uc.pt; Lima, J.J.P. de; Botelho, M.F.; Pacheco, M.F.; Sousa, P.; Bernardo, J.; Ferreira, N.; Goncalves, L.; Aguiar, J.; Providencia, L.A.; Pauwels, E.K.J

    1998-10-01

    The aim of the present study was to investigate the lymphatic cardiac circulation in an experimental model of ischemia plus reperfusion in mongrel dogs (Canis familiaris L). As radiotracer we used 0.2-0.25 ml (111 MBq) of {sup 99m}Tc-Re{sub 2}S{sub 7} colloid ({+-}10 {mu}m), injected subcapsullary below the second diagonal of the descending anterior ligated coronary artery with a special needle. A {gamma}-camera/Starport + DecStation were used for data acquisition. Four experimental groups with five animals each were established: G I = controls; G II = immediately after acute myocardial infarction (AMI); G III = late infarction (5 days after AMI); G IV = ischemia (90 min) + reperfusion. Four regions of interest (ROIs) were chosen: injection area (ZA), above (ZB), near right (ZD), and far right (ZC) from ZA. Mean disappearance times in ZA and dynamic parameters in the other ROIs were determined from activity/time curves drawn in each area, using homemade software. The results obtained seem to indicate that the methodology is appropriate to a detailed study of lymphatic drainage in pathological situations in animal models.

  13. Cardiac Dysfunction in the BACHD Mouse Model of Huntington's Disease.

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    Analyne M Schroeder

    Full Text Available While Huntington's disease (HD is classified as a neurological disorder, HD patients exhibit a high incidence of cardiovascular events leading to heart failure and death. In this study, we sought to better understand the cardiovascular phenotype of HD using the BACHD mouse model. The age-related decline in cardiovascular function was assessed by echocardiograms, electrocardiograms, histological and microarray analysis. We found that structural and functional differences between WT and BACHD hearts start at 3 months of age and continue throughout life. The aged BACHD mice develop cardiac fibrosis and ultimately apoptosis. The BACHD mice exhibited adaptive physiological changes to chronic isoproterenol treatment; however, the medication exacerbated fibrotic lesions in the heart. Gene expression analysis indicated a strong tilt toward apoptosis in the young mutant heart as well as changes in genes involved in cellular metabolism and proliferation. With age, the number of genes with altered expression increased with the large changes occurring in the cardiovascular disease, cellular metabolism, and cellular transport clusters. The BACHD model of HD exhibits a number of changes in cardiovascular function that start early in the disease progress and may provide an explanation for the higher cardiovascular risk in HD.

  14. Emergency department overcrowding: the Emergency Department Cardiac Analogy Model (EDCAM).

    Science.gov (United States)

    Richardson, Sandra K; Ardagh, Michael; Gee, Paul

    2005-01-01

    Increasing patient numbers, changing demographics and altered patient expectations have all contributed to the current problem with 'overcrowding' in emergency departments (EDs). The problem has reached crisis level in a number of countries, with significant implications for patient safety, quality of care, staff 'burnout' and patient and staff satisfaction. There is no single, clear definition of the cause of overcrowding, nor a simple means of addressing the problem. For some hospitals, the option of ambulance diversion has become a necessity, as overcrowded waiting rooms and 'bed-block' force emergency staff to turn patients away. But what are the options when ambulance diversion is not possible? Christchurch Hospital, New Zealand is a tertiary level facility with an emergency department that sees on average 65,000 patients per year. There are no other EDs to whom patients can be diverted, and so despite admission rates from the ED of up to 48%, other options need to be examined. In order to develop a series of unified responses, which acknowledge the multifactorial nature of the problem, the Emergency Department Cardiac Analogy model of ED flow, was developed. This model highlights the need to intervene at each of three key points, in order to address the issue of overcrowding and its associated problems.

  15. Olfaction in dragonflies: electrophysiological evidence.

    Science.gov (United States)

    Rebora, Manuela; Salerno, Gianandrea; Piersanti, Silvana; Dell'otto, Alessandro; Gaino, Elda

    2012-02-01

    The problem of olfaction in Paleoptera (Odonata, Ephemeroptera) cannot be considered fully elucidated until now. These insects have been traditionally considered anosmic, because their brain lacks glomerular antennal lobes, typically involved in Neoptera odor perception. In order to understand if the presumed coeloconic olfactory receptors described on the antennal flagellum of adult Odonata are really functioning, we performed an electrophysiological investigation with electroantennogram (EAG) and single cell recordings (SCR), using Libellula depressa L. (Odonata, Libellulidae) as a model species. Odors representing different chemical classes such as (Z)-3-hexenyl acetate (acetate ester), (E)-2-hexenal, octanal (aldehydes), (Z)-3-hexen-1-ol (alcohol), propionic acid, butyric acid (carboxylic acids), and 1,4-diaminobutane (amine) were tested. Most of the tested chemicals elicited depolarizing EAG responses in both male and female antennae; SCR show unambiguously for the first time the presence of olfactory neurons in the antennae of L. depressa and strongly support the olfactory function of the coeloconic sensilla located on the antennal flagellum of this species. Electrophysiological activity may not necessarily indicate behavioral activity, and the biological role of olfactory responses in Odonata must be determined in behavioral bioassays. This study represents a starting point for further behavioral, electrophysiological, neuroanatomical and molecular investigation on Odonata olfaction, a research field particularly interesting owing to the basal position of Paleoptera, also for tracing evolutionary trends in insect olfaction.

  16. Trigeminal Electrophysiology: a 2 × 2 matrix model for differential diagnosis between temporomandibular disorders and orofacial pain

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    Chessa Giacomo

    2010-07-01

    Full Text Available Abstract Background Pain due to temporomandibular disorders (TMDs often has the same clinical symptoms and signs as other types of orofacial pain (OP. The possible presence of serious neurological and/or systemic organic pathologies makes differential diagnosis difficult, especially in early disease stages. In the present study, we performed a qualitative and quantitative electrophysiological evaluation of the neuromuscular responses of the trigeminal nervous system. Using the jaw jerk reflex (JJ and the motor evoked potentials of the trigeminal roots (bR-MEPs tests, we investigated the functional and organic responses of healthy subjects (control group and patients with TMD symptoms (TMD group. Method Thirty-three patients with temporomandibular disorder (TMD symptoms and 36 control subjects underwent two electromyographic (EMG tests: the jaw jerk reflex test and the motor evoked potentials of the trigeminal roots test using bilateral electrical transcranial stimulation. The mean, standard deviation, median, minimum, and maximum values were computed for the EMG absolute values. The ratio between the EMG values obtained on each side was always computed with the reference side as the numerator. For the TMD group, this side was identified as the painful side (pain side, while for the control group this was taken as the non-preferred masticatory side (non-preferred side. The 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles were also calculated. Results Analysis of the ratios (expressed as percentages between the values obtained on both sides revealed a high degree of symmetry in the bR-MEPs % in the control (0.93 ± 0.12% and TMD (0.91 ± 0.22% groups. This symmetry indicated organic integrity of the trigeminal root motor fibers and correct electrode arrangement. A degree of asymmetry of the jaw jerk's amplitude between sides (ipJJ%, when the mandible was kept in the intercuspal position, was found in the TMD group (0.24% ± 0.14% with a

  17. Trigeminal Electrophysiology: a 2 × 2 matrix model for differential diagnosis between temporomandibular disorders and orofacial pain

    Science.gov (United States)

    2010-01-01

    Background Pain due to temporomandibular disorders (TMDs) often has the same clinical symptoms and signs as other types of orofacial pain (OP). The possible presence of serious neurological and/or systemic organic pathologies makes differential diagnosis difficult, especially in early disease stages. In the present study, we performed a qualitative and quantitative electrophysiological evaluation of the neuromuscular responses of the trigeminal nervous system. Using the jaw jerk reflex (JJ) and the motor evoked potentials of the trigeminal roots (bR-MEPs) tests, we investigated the functional and organic responses of healthy subjects (control group) and patients with TMD symptoms (TMD group). Method Thirty-three patients with temporomandibular disorder (TMD) symptoms and 36 control subjects underwent two electromyographic (EMG) tests: the jaw jerk reflex test and the motor evoked potentials of the trigeminal roots test using bilateral electrical transcranial stimulation. The mean, standard deviation, median, minimum, and maximum values were computed for the EMG absolute values. The ratio between the EMG values obtained on each side was always computed with the reference side as the numerator. For the TMD group, this side was identified as the painful side (pain side), while for the control group this was taken as the non-preferred masticatory side (non-preferred side). The 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles were also calculated. Results Analysis of the ratios (expressed as percentages) between the values obtained on both sides revealed a high degree of symmetry in the bR-MEPs % in the control (0.93 ± 0.12%) and TMD (0.91 ± 0.22%) groups. This symmetry indicated organic integrity of the trigeminal root motor fibers and correct electrode arrangement. A degree of asymmetry of the jaw jerk's amplitude between sides (ipJJ%), when the mandible was kept in the intercuspal position, was found in the TMD group (0.24% ± 0.14%) with a statistically

  18. 3D engineered cardiac tissue models of human heart disease: learning more from our mice.

    Science.gov (United States)

    Ralphe, J Carter; de Lange, Willem J

    2013-02-01

    Mouse engineered cardiac tissue constructs (mECTs) are a new tool available to study human forms of genetic heart disease within the laboratory. The cultured strips of cardiac cells generate physiologic calcium transients and twitch force, and respond to electrical pacing and adrenergic stimulation. The mECT can be made using cells from existing mouse models of cardiac disease, providing a robust readout of contractile performance and allowing a rapid assessment of genotype-phenotype correlations and responses to therapies. mECT represents an efficient and economical extension to the existing tools for studying cardiac physiology. Human ECTs generated from iPSCMs represent the next logical step for this technology and offer significant promise of an integrated, fully human, cardiac tissue model.

  19. Visual electrophysiology in children

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    Jelka Brecelj

    2005-10-01

    Full Text Available Background: Electrophysiological assessment of vision in children helps to recognise abnormal development of the visual system when it is still susceptible to medication and eventual correction. Visual electrophysiology provides information about the function of the retina (retinal pigment epithelium, cone and rod receptors, bipolar, amacrine, and ganglion cells, optic nerve, chiasmal and postchiasmal visual pathway, and visual cortex.Methods: Electroretinograms (ERG and visual evoked potentials (VEP are recorded non-invasively; in infants are recorded simultaneously ERG with skin electrodes, while in older children separately ERG with HK loop electrode in accordance with ISCEV (International Society for Clinical Electrophysiology of Vision recommendations.Results: Clinical and electrophysiological changes in children with nystagmus, Leber’s congenital amaurosis, achromatopsia, congenital stationary night blindness, progressive retinal dystrophies, optic nerve hypoplasia, albinism, achiasmia, optic neuritis and visual pathway tumours are presented.Conclusions: Electrophysiological tests can help to indicate the nature and the location of dysfunction in unclear ophthalmological and/or neurological cases.

  20. Historical perspectives on interventional electrophysiology.

    Science.gov (United States)

    Lüderitz, Berndt

    2003-10-01

    The history of interventional electrophysiology is long and fascinating. In the beginning, there is not simply the anatomy and physiology of the heart, but also analysis of the pulse, which indicates the activity of the heart. The analysis of the (peripheral) pulse as a mechanical expression of heart activity goes back several millennia. In China, in 280 B.C., Wang Chu Ho wrote ten books about the pulse. The Greeks called the pulse "sphygmos", and the sphygmology thus deals with a theory of this natural occurrence. In Roman times, Galen interpreted the various types of pulse according to the widespread presumption of the time, that each organ in every disease has its own form of pulse. The basic tool for arrhythmia diagnosis became the electrocardiography introduced by Willem Einthoven who obtained the first human electrogram 1902 in Leiden, The Netherlands. The growing clinical importance of electrical cardiac stimulation has been recognized and renewed as Zoll (1911-1999) in 1952 reported a successful resuscitation in cardiac standstill by external stimulation. Meanwhile all over the world, millions of patients with cardiac arrhythmias have been treated with pacemakers in the last 45 years. The concept of a fully automatic implantable cardioverter-defibrillator system (ICD) for recognition and treatment of ventricular tachyarrhythmias was first suggested in 1970. The first implantation of the device in a human being was performed in February 1980. Further developments concern atrial and atrioventricular defibrillators, radiofrequency ablation, laser therapy and advanced antiarrhythmic surgery, new antiarrhythmic drugs and sophisticated devices for preventive pacing. The advances in the field of diagnostic and therapeutic application of pharmacologic and electrical tools as well as alternative methods will continue as rapidly as before in order to give us further significant aid in taking care of the patient.

  1. Electrophysiological effects of cetirizine, astemizole and D-sotalol in a canine model of long QT syndrome.

    Science.gov (United States)

    Weissenburger, J; Noyer, M; Cheymol, G; Jaillon, P

    1999-07-01

    Observations of torsades de pointes during therapy with terfenadine and astemizole has raised concern about the cardiac safety of non-sedating H1-antagonist agents. We compared cetirizine, another compound of that class, to D-sotalol and to astemizole in a model of acquired long QT syndrome. Open-chest surgery was performed in adult beagle dogs anaesthetized with halothane and thiopental. Bradycardia was produced with beta-adrenergic blockade and sinus node crush. Four left ventricular intramyocardial unipolar monophasic action potentials (MAP) were recorded during atrial pacing at basic cycle lengths (BCL) 400-1500 msec, before and during three successive 1-h drug infusions (0.14, 0.45 and 1.4 mg/kg/h for astemizole and cetirizine and 1.1, 2.2 and 4.5 mg/kg/h for D-sotalol). Dose- and bradycardia-dependent prolongations of MAP duration (MAPD) were produced by D-sotalol (P < 0.001) and astemizole (P < 0.001) but not by cetirizine. At BCL 1500 ms, the three infusions of astemizole prolonged endocardial MAPD from 323 +/- 8 msec (mean +/- SE) at baseline to 343 +/- 10, 379 +/- 13 and 468 +/- 26 msec, respectively (n = 9). Sotalol prolonged that MAPD from 339 +/- 6 msec to 377 +/- 7, 444 +/- 15 and 485 +/- 24 msec (n = 7). In contrast, cetirizine did not prolong MAPD: 341 +/- 8 msec at baseline Vs 330 +/- 8, 324 +/- 9 and 323 +/- 11 msec (n = 9). Drug-induced increase in transmural dispersion reached +79 +/- 19 msec after astemizole, +59 +/- 21 msec after D-sotalol and only +7 +/- 11 msec after cetirizine. Runs of ventricular tachycardias and torsades de pointes occurred during dose three of astemizole (5/9 dogs) and D-sotalol (4/7 dogs) but never during cetirizine. In the present model, astemizole and D-sotalol but not cetirizine prolonged MAPD and transmural dispersions of repolarization and produced torsades de pointes. These results suggest that the halothane-anaesthetized bradycardic dog could be a valuable model to discriminate drugs for their class III effects

  2. Electrophysiological Endophenotypes for Schizophrenia.

    Science.gov (United States)

    Owens, Emily M; Bachman, Peter; Glahn, David C; Bearden, Carrie E

    2016-01-01

    Endophenotypes are quantitative, heritable traits that may help to elucidate the pathophysiologic mechanisms underlying complex disease syndromes, such as schizophrenia. They can be assessed at numerous levels of analysis; here, we review electrophysiological endophenotypes that have shown promise in helping us understand schizophrenia from a more mechanistic point of view. For each endophenotype, we describe typical experimental procedures, reliability, heritability, and reported gene and neurobiological associations. We discuss recent findings regarding the genetic architecture of specific electrophysiological endophenotypes, as well as converging evidence from EEG studies implicating disrupted balance of glutamatergic signaling and GABAergic inhibition in the pathophysiology of schizophrenia. We conclude that refining the measurement of electrophysiological endophenotypes, expanding genetic association studies, and integrating data sets are important next steps for understanding the mechanisms that connect identified genetic risk loci for schizophrenia to the disease phenotype.

  3. Effects of decompression on behavioral, electrophysiologic, and histomorphologic recovery in a chronic sciatic nerve compression model of streptozotocin-induced diabetic rats

    Science.gov (United States)

    Wang, Ping-Hui; Yang, Cheng-Chang; Su, Wei-Ren; Wu, Po-Ting; Cheng, Shun-Chien; Jou, I-Ming

    2017-01-01

    Purpose To determine susceptibility to decompression surgery in diabetic and nondiabetic peripheral neuropathy using a chronic compression neuropathy model. Materials and methods Twenty-four streptozotocin-induced diabetic rats were randomly divided into three groups: group I, chronic compression of the left sciatic nerve for 4 weeks with decompression; group II, similar without decompression; and group III, sham exposing the sciatic nerve only. The other 24 nondiabetic rats were assigned to groups IV–VI, which received compression–decompression, compression, and the sham operation, respectively. Mixed-nerve-elicited somatosensory evoked potentials (M-SSEPs) and compound muscle action potentials (CMAPs) were measured to verify the compression neuropathy in the posttreatment follow-up. Behavioral observations in thermal hyperalgesia tests were quantified before electrophysiologic examinations. Treated and contralateral nerves were harvested for histomorphologic analysis. Results Chronic compression of sciatic nerve induced significant reduction of amplitude and increment of latency of M-SSEP and CMAP in both diabetic and nondiabetic rats. Diabetic group changes were more susceptible. Decompression surgery significantly improved both sensory and motor conduction, thermal hyperalgesia, and the mean myelin diameter of the rat sciatic nerve in both diabetic and nondiabetic groups. Near full recovery of motor and sensory function occurred in the nondiabetic rats, but not in the diabetic rats 8 weeks postdecompression. Conclusion Behavioral, electrophysiologic, and histomorphologic findings indicate that decompression surgery is effective in both diabetic and nondiabetic peripheral neuropathy.

  4. Small and large animal models in cardiac contraction research: advantages and disadvantages.

    Science.gov (United States)

    Milani-Nejad, Nima; Janssen, Paul M L

    2014-03-01

    The mammalian heart is responsible for not only pumping blood throughout the body but also adjusting this pumping activity quickly depending upon sudden changes in the metabolic demands of the body. For the most part, the human heart is capable of performing its duties without complications; however, throughout many decades of use, at some point this system encounters problems. Research into the heart's activities during healthy states and during adverse impacts that occur in disease states is necessary in order to strategize novel treatment options to ultimately prolong and improve patients' lives. Animal models are an important aspect of cardiac research where a variety of cardiac processes and therapeutic targets can be studied. However, there are differences between the heart of a human being and an animal and depending on the specific animal, these differences can become more pronounced and in certain cases limiting. There is no ideal animal model available for cardiac research, the use of each animal model is accompanied with its own set of advantages and disadvantages. In this review, we will discuss these advantages and disadvantages of commonly used laboratory animals including mouse, rat, rabbit, canine, swine, and sheep. Since the goal of cardiac research is to enhance our understanding of human health and disease and help improve clinical outcomes, we will also discuss the role of human cardiac tissue in cardiac research. This review will focus on the cardiac ventricular contractile and relaxation kinetics of humans and animal models in order to illustrate these differences.

  5. Functional imaging and modeling of the heart. Proceedings

    Energy Technology Data Exchange (ETDEWEB)

    Sachse, F.B. [Utah Univ., Salt Lake City, UT (United States). Nora Eccles Harrison Cardiovascular Research and Training Institute; Seemann, G. (eds.) [Karlsruhe Univ. (Germany). Inst. fuer Biomedizinische Technik

    2007-07-01

    Functional imaging and modeling constitute important research approaches to gaining insights into physiology and pathophysiology of the human heart. Applications of these approaches are promising to support clinical diagnosis and therapy of cardiac diseases, which are the most common cause of death in the western world and a major health problem in Asia. The book contains 48 contributions concerning the following topics: Imaging and image analysis, cardiac electrophysiology, electro- and magnetocardiography, cardiac mechanics and clinical applications, imaging and anatomic modeling.

  6. Electrophysiological Characteristics of Embryonic Stem Cell-Derived Cardiomyocytes are Cell Line-Dependent

    Directory of Open Access Journals (Sweden)

    Tobias Hannes

    2015-01-01

    Full Text Available Background: Modelling of cardiac development, physiology and pharmacology by differentiation of embryonic stem cells (ESCs requires comparability of cardiac differentiation between different ESC lines. To investigate whether the outcome of cardiac differentiation is consistent between different ESC lines, we compared electrophysiological properties of ESC-derived cardiomyocytes (ESC-CMs of different murine ESC lines. Methods: Two wild-type (D3 and R1 and two transgenic ESC lines (D3/aPIG44 and CGR8/AMPIGX-7 were differentiated under identical culture conditions. The transgenic cell lines expressed enhanced green fluorescent protein (eGFP and puromycin-N-acetyltransferase under control of the cardiac specific α-myosin heavy chain (αMHC promoter. Action potentials (APs were recorded using sharp electrodes and multielectrode arrays in beating clusters of ESC-CMs. Results: Spontaneous AP frequency and AP duration (APD as well as maximal upstroke velocity differed markedly between unpurified CMs of the four ESC lines. APD heterogeneity was negligible in D3/aPIG44, moderate in D3 and R1 and extensive in CGR8/AMPIGX-7. Interspike intervals calculated from long-term recordings showed a high degree of variability within and between recordings in CGR8/AMPIGX-7, but not in D3/aPIG44. Purification of the αMHC+ population by puromycin treatment posed only minor changes to APD in D3/aPIG44, but significantly shortened APD in CGR8/AMPIGX-7. Conclusion: Electrophysiological properties of ESC-CMs are strongly cell line-dependent and can be influenced by purification of cardiomyocytes by antibiotic selection. Thus, conclusions on cardiac development, physiology and pharmacology derived from single stem cell lines have to be interpreted carefully.

  7. Inhalation of diesel exhaust does not exacerbate cardiac hypertrophy or heart failure in two mouse models of cardiac hypertrophy.

    Science.gov (United States)

    Liu, Yonggang; Chien, Wei-Ming; Medvedev, Ivan O; Weldy, Chad S; Luchtel, Daniel L; Rosenfeld, Michael E; Chin, Michael T

    2013-10-05

    Strong associations have been observed between exposure to fine ambient particulate matter (PM2.5) and adverse cardiovascular outcomes. In particular, exposure to traffic related PM2.5 has been associated with increases in left ventricular hypertrophy, a strong risk factor for cardiovascular mortality. As much of traffic related PM2.5 is derived from diesel exhaust (DE), we investigated the effects of chronic DE exposure on cardiac hypertrophy and heart failure in the adult mouse by exposing mice to DE combined with either of two mouse models of cardiac hypertrophy: angiotensin II infusion or pressure overload induced by transverse aortic banding. Wild type male C57BL/6 J mice were either infused with angiotensin II (800 ng/kg/min) via osmotic minipump implanted subcutaneously for 1 month, or underwent transverse aortic banding (27 gauge needle 1 week for observing acute reactions, 26 gauge needle 3 months or 6 months for observing chronic reactions). Vehicle (saline) infusion or sham surgery was used as a control. Shortly after surgery, mice were transferred to our exposure facility and randomly assigned to either diesel exhaust (300 or 400 μg/m(3)) or filtered air exposures. After reaching the end of designated time points, echocardiography was performed to measure heart structure and function. Gravimetric analysis was used to measure the ventricular weight to body weight ratio. We also measured heart rate by telemetry using implanted ambulatory ECG monitors. Both angiotensin II and transverse aortic banding promoted cardiac hypertrophy compared to vehicle or sham controls. Transverse aortic banding for six months also promoted heart failure in addition to cardiac hypertrophy. In all cases, DE failed to exacerbate the development of hypertrophy or heart failure when compared to filtered air controls. Prolonged DE exposure also led to a decrease in average heart rate. Up to 6-months of DE exposure had no effect on cardiac hypertrophy and heart function induced by

  8. Diet-induced pre-diabetes slows cardiac conductance and promotes arrhythmogenesis

    DEFF Research Database (Denmark)

    Axelsen, Lene Nygaard; Callø, Kirstine; Braunstein, Thomas Hartig;

    2015-01-01

    a significant increase in cardiac triglyceride content (1.93 ± 0.19 (n = 12) vs. 0.77 ± 0.13 nmol/mg (n = 12), p cause electrophysiological changes, which leads to QRS prolongation, decreased conduction velocity and increased arrhythmogenesis during......BACKGROUND: Type 2 diabetes is associated with abnormal electrical conduction and sudden cardiac death, but the pathogenic mechanism remains unknown. This study describes electrophysiological alterations in a diet-induced pre-diabetic rat model and examines the underlying mechanism. METHODS....... Conduction velocity was examined in isolated tissue strips. Ion channel and gap junction conductances were analyzed by patch-clamp studies in isolated cardiomyocytes. Fibrosis was examined by Masson's Trichrome staining and thin-layer chromatography was used to analyze cardiac lipid content. Connexin43 (Cx43...

  9. Overexpression of Dyrk1A is implicated in several cognitive, electrophysiological and neuromorphological alterations found in a mouse model of Down syndrome.

    Directory of Open Access Journals (Sweden)

    Susana García-Cerro

    Full Text Available Down syndrome (DS phenotypes result from the overexpression of several dosage-sensitive genes. The DYRK1A (dual-specificity tyrosine-(Y-phosphorylation regulated kinase 1A gene, which has been implicated in the behavioral and neuronal alterations that are characteristic of DS, plays a role in neuronal progenitor proliferation, neuronal differentiation and long-term potentiation (LTP mechanisms that contribute to the cognitive deficits found in DS. The purpose of this study was to evaluate the effect of Dyrk1A overexpression on the behavioral and cognitive alterations in the Ts65Dn (TS mouse model, which is the most commonly utilized mouse model of DS, as well as on several neuromorphological and electrophysiological properties proposed to underlie these deficits. In this study, we analyzed the phenotypic differences in the progeny obtained from crosses of TS females and heterozygous Dyrk1A (+/- male mice. Our results revealed that normalization of the Dyrk1A copy number in TS mice improved working and reference memory based on the Morris water maze and contextual conditioning based on the fear conditioning test and rescued hippocampal LTP. Concomitant with these functional improvements, normalization of the Dyrk1A expression level in TS mice restored the proliferation and differentiation of hippocampal cells in the adult dentate gyrus (DG and the density of GABAergic and glutamatergic synapse markers in the molecular layer of the hippocampus. However, normalization of the Dyrk1A gene dosage did not affect other structural (e.g., the density of mature hippocampal granule cells, the DG volume and the subgranular zone area or behavioral (i.e., hyperactivity/attention alterations found in the TS mouse. These results suggest that Dyrk1A overexpression is involved in some of the cognitive, electrophysiological and neuromorphological alterations, but not in the structural alterations found in DS, and suggest that pharmacological strategies targeting

  10. Cardiac remodeling in the mouse model of Marfan syndrome develops into two distinctive phenotypes.

    Science.gov (United States)

    Tae, Hyun-Jin; Petrashevskaya, Natalia; Marshall, Shannon; Krawczyk, Melissa; Talan, Mark

    2016-01-15

    Marfan syndrome (MFS) is a systemic disorder of connective tissue caused by mutations in fibrillin-1. Cardiac dysfunction in MFS has not been characterized halting the development of therapies of cardiac complication in MFS. We aimed to study the age-dependent cardiac remodeling in the mouse model of MFS FbnC1039G+/- mouse [Marfan heterozygous (HT) mouse] and its association with valvular regurgitation. Marfan HT mice of 2-4 mo demonstrated a mild hypertrophic cardiac remodeling with predominant decline of diastolic function and increased transforming growth factor-β canonical (p-SMAD2/3) and noncanonical (p-ERK1/2 and p-p38 MAPK) signaling and upregulation of hypertrophic markers natriuretic peptides atrium natriuretic peptide and brain natriuretic peptide. Among older HT mice (6-14 mo), cardiac remodeling was associated with two distinct phenotypes, manifesting either dilated or constricted left ventricular chamber. Dilatation of left ventricular chamber was accompanied by biochemical evidence of greater mechanical stress, including elevated ERK1/2 and p38 MAPK phosphorylation and higher brain natriuretic peptide expression. The aortic valve regurgitation was registered in 20% of the constricted group and 60% of the dilated group, whereas mitral insufficiency was observed in 40% of the constricted group and 100% of the dilated group. Cardiac dysfunction was not associated with the increase of interstitial fibrosis and nonmyocyte proliferation. In the mouse model fibrillin-1, haploinsufficiency results in the early onset of nonfibrotic hypertrophic cardiac remodeling and dysfunction, independently from valvular abnormalities. MFS heart is vulnerable to stress-induced cardiac dilatation in the face of valvular regurgitation, and stress-activated MAPK signals represent a potential target for cardiac management in MFS.

  11. The ET axis mediates arrhythmogenesis and compromised cardiac function in two cardiomyopathy models

    Institute of Scientific and Technical Information of China (English)

    YuFENG; De-zaiDAI; YuanZHANG; Hai-boHE; Min-youQI; YinDAI; FengYU

    2005-01-01

    AIM Endothelin 1(ET-1), a potent vasoconstrictor peptide, is also regarded as an important etiological factor involved in many cardiac diseases like heart failure and cardiac hypertrophy. It mediates pathologic changes by forming an """"ET axis"""" at the upstream to ion channels, such as stimulating oxidant stress, eliciting cardiac remodeling by proliferation of cardiomyocytes, inducing apoptosis, affecting signal transduction pathway, and modulating intranuclear gene transcription. The purpose of this study was to investigate the pivotal role by ET axis in worsening arrhythmias and cardiac function in experimental hypertrophic cardiomyopathy (HCM) and heart failure (HF) models. METHODS The rat HCM model was induced by s.c L-thyroxin (L-thy, 0.2mg/Kg/d) for 10d,

  12. Comprehensive multilevel in vivo and in vitro analysis of heart rate fluctuations in mice by ECG telemetry and electrophysiology.

    Science.gov (United States)

    Fenske, Stefanie; Pröbstle, Rasmus; Auer, Franziska; Hassan, Sami; Marks, Vanessa; Pauza, Danius H; Biel, Martin; Wahl-Schott, Christian

    2016-01-01

    The normal heartbeat slightly fluctuates around a mean value; this phenomenon is called physiological heart rate variability (HRV). It is well known that altered HRV is a risk factor for sudden cardiac death. The availability of genetic mouse models makes it possible to experimentally dissect the mechanism of pathological changes in HRV and its relation to sudden cardiac death. Here we provide a protocol that allows for a comprehensive multilevel analysis of heart rate (HR) fluctuations. The protocol comprises a set of techniques that include in vivo telemetry and in vitro electrophysiology of intact sinoatrial network preparations or isolated single sinoatrial node (SAN) cells. In vitro preparations can be completed within a few hours, with data acquisition within 1 d. In vivo telemetric ECG requires 1 h for surgery and several weeks for data acquisition and analysis. This protocol is of interest to researchers investigating cardiovascular physiology and the pathophysiology of sudden cardiac death.

  13. Cardiac fibroblast-derived extracellular matrix (biomatrix) as a model for the studies of cardiac primitive cell biological properties in normal and pathological adult human heart.

    Science.gov (United States)

    Castaldo, Clotilde; Di Meglio, Franca; Miraglia, Rita; Sacco, Anna Maria; Romano, Veronica; Bancone, Ciro; Della Corte, Alessandro; Montagnani, Stefania; Nurzynska, Daria

    2013-01-01

    Cardiac tissue regeneration is guided by stem cells and their microenvironment. It has been recently described that both cardiac stem/primitive cells and extracellular matrix (ECM) change in pathological conditions. This study describes the method for the production of ECM typical of adult human heart in the normal and pathological conditions (ischemic heart disease) and highlights the potential use of cardiac fibroblast-derived ECM for in vitro studies of the interactions between ECM components and cardiac primitive cells responsible for tissue regeneration. Fibroblasts isolated from adult human normal and pathological heart with ischemic cardiomyopathy were cultured to obtain extracellular matrix (biomatrix), composed of typical extracellular matrix proteins, such as collagen and fibronectin, and matricellular proteins, laminin, and tenascin. After decellularization, this substrate was used to assess biological properties of cardiac primitive cells: proliferation and migration were stimulated by biomatrix from normal heart, while both types of biomatrix protected cardiac primitive cells from apoptosis. Our model can be used for studies of cell-matrix interactions and help to determine the biochemical cues that regulate cardiac primitive cell biological properties and guide cardiac tissue regeneration.

  14. Cardiac Fibroblast-Derived Extracellular Matrix (Biomatrix as a Model for the Studies of Cardiac Primitive Cell Biological Properties in Normal and Pathological Adult Human Heart

    Directory of Open Access Journals (Sweden)

    Clotilde Castaldo

    2013-01-01

    Full Text Available Cardiac tissue regeneration is guided by stem cells and their microenvironment. It has been recently described that both cardiac stem/primitive cells and extracellular matrix (ECM change in pathological conditions. This study describes the method for the production of ECM typical of adult human heart in the normal and pathological conditions (ischemic heart disease and highlights the potential use of cardiac fibroblast-derived ECM for in vitro studies of the interactions between ECM components and cardiac primitive cells responsible for tissue regeneration. Fibroblasts isolated from adult human normal and pathological heart with ischemic cardiomyopathy were cultured to obtain extracellular matrix (biomatrix, composed of typical extracellular matrix proteins, such as collagen and fibronectin, and matricellular proteins, laminin, and tenascin. After decellularization, this substrate was used to assess biological properties of cardiac primitive cells: proliferation and migration were stimulated by biomatrix from normal heart, while both types of biomatrix protected cardiac primitive cells from apoptosis. Our model can be used for studies of cell-matrix interactions and help to determine the biochemical cues that regulate cardiac primitive cell biological properties and guide cardiac tissue regeneration.

  15. Control of spiral waves and turbulent states in a cardiac model by travelling-wave perturbations

    Institute of Scientific and Technical Information of China (English)

    王鹏业; 谢平; 尹华伟

    2003-01-01

    We propose a travelling-wave perturbation method to control the spatiotemporal dynamics in a cardiac model.It is numerically demonstrated that the method can successfully suppress the wave instability(alternans in action potential duration) in the one-dimensional case and convert spiral waves and turbulent states to the normal travelling wave states in the two-dimensional case.An experimental scheme is suggested which may provide a new design for a cardiac defibrillator.

  16. Electrophysiological characteristics of cardiocyte from excised pulmonary vein cardiac muscle of rabbit%离体兔肺静脉肌袖心肌细胞电生理特性

    Institute of Scientific and Technical Information of China (English)

    刘俊辉; 李源; 刘泰槰; 黄卫斌

    2011-01-01

    目的 应用常规玻璃微电极细胞内记录技术,研究家兔肺静脉肌袖(PVC)电生理特性,观察PVC与左心房心肌细胞(LAC)之间的电传导现象,探讨肺静脉起源的阵发性房颤的发生机制.方法 50只健康成年家兔,获取肺静脉及相连左房心肌组织,应用常规微电极细胞内技术:记录PVC与LAC动作电位(AP),并进行各项参数比较(APD20,APD50,APD90);分别于PVC端和LAC端予不同频率脉冲刺激,观察另一端AP的产生情况;改用加有钾离子通道阻滞剂2mmol/L氯化铯(CsCl)的台式液,观察二者早后除极(EAD)发生的可能性.结果 PVC的APD20,APD50,APD90均较LAC长(APD20 (23.09±5.44)ms vs (19.50±1.66)ms,APD50 (52.40±7.93)ms vs (28.90±4.36)ms,APD90 (123.35±8.26)ms vs (69.65±9.44)ms),均有显著性差异(P均<0.05);在一定的刺激频率范围内,肺静脉的刺激均能传导至左心房,而后者较少能逆传至肺静脉(100% vs 10%,P<0.05);加用药物灌流后,PVC更易发生EAD(90% vs 15%,P<0.05).结论 PVC和LAC之间的电兴奋传导是不均一的,这可能是形成折返的基础.CsCl作为一种K+通道阻滞剂能延长复极过程,为后除极的发生创造条件,PVC的长AP时程特性,具备发生EAD的倾向性,并且兴奋易于传入左心房,这可能是促进房性心律失常的发生基础.%Objective It is to study the electrophysiological characteristics of cardiocyte from pulmonary vein cardiac muscle ( PVC ) of rabbit applying intracellular recording technique of routine glass microelectrode, to observe the electrical conduction between PVC and left atrium cardiocyte ( LAC ) and to approach the mechanism of paroxysmal atrial fibrillation originated from pulmonary vein. Methods Multiple cardiocytes preparations from pulmonary vein and left atrium of 50 healthy adult rabbits were obtained. The routine intracellular microelectrode technique was applied to record action potential ( AP ) of PVC and LAC , and a comparison of action potential duration

  17. A discrete electromechanical model for human cardiac tissue: effects of stretch-activated currents and stretch conditions on restitution properties and spiral wave dynamics.

    Directory of Open Access Journals (Sweden)

    Louis D Weise

    Full Text Available We introduce an electromechanical model for human cardiac tissue which couples a biophysical model of cardiac excitation (Tusscher, Noble, Noble, Panfilov, 2006 and tension development (adjusted Niederer, Hunter, Smith, 2006 model with a discrete elastic mass-lattice model. The equations for the excitation processes are solved with a finite difference approach, and the equations of the mass-lattice model are solved using Verlet integration. This allows the coupled problem to be solved with high numerical resolution. Passive mechanical properties of the mass-lattice model are described by a generalized Hooke's law for finite deformations (Seth material. Active mechanical contraction is initiated by changes of the intracellular calcium concentration, which is a variable of the electrical model. Mechanical deformation feeds back on the electrophysiology via stretch-activated ion channels whose conductivity is controlled by the local stretch of the medium. We apply the model to study how stretch-activated currents affect the action potential shape, restitution properties, and dynamics of spiral waves, under constant stretch, and dynamic stretch caused by active mechanical contraction. We find that stretch conditions substantially affect these properties via stretch-activated currents. In constantly stretched medium, we observe a substantial decrease in conduction velocity, and an increase of action potential duration; whereas, with dynamic stretch, action potential duration is increased only slightly, and the conduction velocity restitution curve becomes biphasic. Moreover, in constantly stretched medium, we find an increase of the core size and period of a spiral wave, but no change in rotation dynamics; in contrast, in the dynamically stretching medium, we observe spiral drift. Our results may be important to understand how altered stretch conditions affect the heart's functioning.

  18. Electrophysiological safety of sertindole in dogs with normal and remodeled hearts

    DEFF Research Database (Denmark)

    Thomsen, Morten Bækgaard; Volders, Paul G A; Stengl, Milan

    2003-01-01

    Inhibition of the potassium current IKr and QT prolongation are associated with drug-induced torsades de pointes arrhythmias (TdP) and sudden cardiac death. We investigated the cardiac electrophysiological effects of sertindole, an antipsychotic drug reported to prolong the QT interval in schizop...

  19. A Rodent Model of Cardiac Donation After Circulatory Death and Novel Biomarkers of Cardiac Viability During Ex Vivo Heart Perfusion.

    Science.gov (United States)

    Kearns, Mark J; Miller, Sally D; Cheung, Anson; Bashir, Jamil; Wong, Stephanie; Seidman, Michael A; Boyd, John H

    2017-08-01

    Organ donation after circulatory death (DCD) is increasingly being used as a means of addressing the organ supply/demand mismatch in solid organ transplantation. There is reluctance to use DCD hearts, due to an inability to precisely identify hearts that have suffered irreversible injury. We investigated novel biomarkers and clinically relevant endpoints across a spectrum of warm ischemic times, before and during ex vivo heart perfusion (EVHP), to identify features associated with a nonviable cardiac phenotype. Donor rats sustained a hypoxic cardiac arrest, followed by variable acirculatory standoff periods (DCD groups). Left ventricular function, histochemical injury, and differences in left ventricular gene expression were studied before, and during, EVHP. As warm ischemic time exposure increased in DCD groups, fewer hearts were functional during EVHP, and ventricular function was increasingly impaired. Histochemical assessment identified severely injured hearts during EVHP. A novel gene expression signature identified severely injured hearts during EVHP (upregulation of c-Jun, 3.19 (2.84-3.60); P = 0.0014; HMOX-1, 3.87 (2.72-5.50); P = 0.0037; and Hsp90, 7.66 (6.32-9.27); P < 0.0001 in DCD20), and may be useful in identifying high-risk hearts at the point of harvest (Hsp90). We demonstrate that our preclinical model recapitulates the cardio-respiratory decompensation observed in humans, and that EVHP appears necessary to unmask distinguishing features of severely injured DCD hearts. Furthermore, we outline a clinically relevant multimodal approach to assessing candidate DCD hearts. Novel mRNA signatures correlated with elevations in cardiac Troponin-I in severely injured hearts during EVHP, and may also detect injury at the point of harvest.

  20. Reentry Near the Percolation Threshold in a Heterogeneous Discrete Model for Cardiac Tissue

    Science.gov (United States)

    Alonso, Sergio; Bär, Markus

    2013-04-01

    Arrhythmias in cardiac tissue are related to irregular electrical wave propagation in the heart. Cardiac tissue is formed by a discrete cell network, which is often heterogeneous. A localized region with a fraction of nonconducting links surrounded by homogeneous conducting tissue can become a source of reentry and ectopic beats. Extensive simulations in a discrete model of cardiac tissue show that a wave crossing a heterogeneous region of cardiac tissue can disintegrate into irregular patterns, provided the fraction of nonconducting links is close to the percolation threshold of the cell network. The dependence of the reentry probability on this fraction, the system size, and the degree of excitability can be inferred from the size distribution of nonconducting clusters near the percolation threshold.

  1. Effects of Panax notoginseng saponin Rg1 on cardiac electrophysiological properties and ventricular fibrillation threshold in dogs%三七皂甙Rg1对犬心电生理特性及心室纤颤阈值的影响

    Institute of Scientific and Technical Information of China (English)

    伍卫; 张旭明; 刘品明; 李健明; 王景峰

    1995-01-01

    AIM: To study the effects of Rg1 isolated from saponins of Panac notoginseng on cardiac electrophysiological properties and ventricular fibrillation threshold (VFT). METHODS:Seventeen open-chest dogs were randomly allocated into a Rg1 group (20 mg kg-1, iv) and a control group. The electrophysiological variables and VFT were evaluated by standard electric stimuli and monophasic action potential (MAP) recording. RESULTS: Rg1 prolonged sinus node recovery time (SNRT) by 19. 1 %, AV conduction Wenckebach cycle length (AVWCL) by 7.1%, and ventricular effective refractory period (VERP) by 7.9 %.It prolonged ventricular MAPD30, MAPD50,and MAPD90 by 25.5 %, 24.2 %, and 13.5 %, respectively. VFT was increased by 19.2 %. CONCLUSION: Rg1 prolonged ventricular refractoriness and repolarization, and increased VFT. It was indicated that cardiac electrophysiological effects of Rg1 were similar to those of amiodarone.%目的:研究三七皂甙Rg1对心肌电生理特性及室颤阈值(VFT)的影响.方法:17只正常犬被随机分为生理盐水对照组和Rg1组(20 mgkg-1,iv).麻醉后沿正中开胸,暴露心脏.应用心脏电刺激及单相动作电位(MAP)记录技术,测量心肌电生理参数及VFT.结果:Rg1延长窦房结恢复时间19.1%;延长房室传导文氏阻滞周长7.1%;延长心室有效不应期7.9%;延长心室MAP时程(MAPD),其中MAPD30延长25.5%,MAPD50延长24.2%,MAPD90延长13.5%;提高VFT 19.2%.结论:Rg1延长心室不应性及复极化时程,提高VFT,提示Rg1的作用与胺碘酮的效应类似.

  2. High resolution 3-Dimensional imaging of the human cardiac conduction system from microanatomy to mathematical modeling.

    Science.gov (United States)

    Stephenson, Robert S; Atkinson, Andrew; Kottas, Petros; Perde, Filip; Jafarzadeh, Fatemeh; Bateman, Mike; Iaizzo, Paul A; Zhao, Jichao; Zhang, Henggui; Anderson, Robert H; Jarvis, Jonathan C; Dobrzynski, Halina

    2017-08-03

    Cardiac arrhythmias and conduction disturbances are accompanied by structural remodelling of the specialised cardiomyocytes known collectively as the cardiac conduction system. Here, using contrast enhanced micro-computed tomography, we present, in attitudinally appropriate fashion, the first 3-dimensional representations of the cardiac conduction system within the intact human heart. We show that cardiomyocyte orientation can be extracted from these datasets at spatial resolutions approaching the single cell. These data show that commonly accepted anatomical representations are oversimplified. We have incorporated the high-resolution anatomical data into mathematical simulations of cardiac electrical depolarisation. The data presented should have multidisciplinary impact. Since the rate of depolarisation is dictated by cardiac microstructure, and the precise orientation of the cardiomyocytes, our data should improve the fidelity of mathematical models. By showing the precise 3-dimensional relationships between the cardiac conduction system and surrounding structures, we provide new insights relevant to valvar replacement surgery and ablation therapies. We also offer a practical method for investigation of remodelling in disease, and thus, virtual pathology and archiving. Such data presented as 3D images or 3D printed models, will inform discussions between medical teams and their patients, and aid the education of medical and surgical trainees.

  3. Registry of Malignant Arrhythmias and Sudden Cardiac Death - Influence of Diagnostics and Interventions

    Science.gov (United States)

    2016-11-30

    Ventricular Tachycardia; Ventricular Fibrillation; Sudden Cardiac Death; Coronary Angiography; Electrophysiologic Testing (EP); Catheter Ablation; Percutaneous Coronary Intervention (PCI); Internal Cardioverter Defibrillator (ICD)

  4. Mapping cardiac fiber orientations from high-resolution DTI to high-frequency 3D ultrasound

    Science.gov (United States)

    Qin, Xulei; Wang, Silun; Shen, Ming; Zhang, Xiaodong; Wagner, Mary B.; Fei, Baowei

    2014-03-01

    The orientation of cardiac fibers affects the anatomical, mechanical, and electrophysiological properties of the heart. Although echocardiography is the most common imaging modality in clinical cardiac examination, it can only provide the cardiac geometry or motion information without cardiac fiber orientations. If the patient's cardiac fiber orientations can be mapped to his/her echocardiography images in clinical examinations, it may provide quantitative measures for diagnosis, personalized modeling, and image-guided cardiac therapies. Therefore, this project addresses the feasibility of mapping personalized cardiac fiber orientations to three-dimensional (3D) ultrasound image volumes. First, the geometry of the heart extracted from the MRI is translated to 3D ultrasound by rigid and deformable registration. Deformation fields between both geometries from MRI and ultrasound are obtained after registration. Three different deformable registration methods were utilized for the MRI-ultrasound registration. Finally, the cardiac fiber orientations imaged by DTI are mapped to ultrasound volumes based on the extracted deformation fields. Moreover, this study also demonstrated the ability to simulate electricity activations during the cardiac resynchronization therapy (CRT) process. The proposed method has been validated in two rat hearts and three canine hearts. After MRI/ultrasound image registration, the Dice similarity scores were more than 90% and the corresponding target errors were less than 0.25 mm. This proposed approach can provide cardiac fiber orientations to ultrasound images and can have a variety of potential applications in cardiac imaging.

  5. Developing a novel comprehensive framework for the investigation of cellular and whole heart electrophysiology in the in situ human heart: historical perspectives, current progress and future prospects.

    Science.gov (United States)

    Taggart, Peter; Orini, Michele; Hanson, Ben; Hayward, Martin; Clayton, Richard; Dobrzynski, Halina; Yanni, Joseph; Boyett, Mark; Lambiase, Pier D

    2014-08-01

    Understanding the mechanisms of fatal ventricular arrhythmias is of great importance. In view of the many electrophysiological differences that exist between animal species and humans, the acquisition of basic electrophysiological data in the intact human heart is essential to drive and complement experimental work in animal and in-silico models. Over the years techniques have been developed to obtain basic electrophysiological signals directly from the patients by incorporating these measurements into routine clinical procedures which access the heart such as cardiac catheterisation and cardiac surgery. Early recordings with monophasic action potentials provided valuable information including normal values for the in vivo human heart, cycle length dependent properties, the effect of ischaemia, autonomic nervous system activity, and mechano-electric interaction. Transmural recordings addressed the controversial issue of the mid myocardial "M" cell. More recently, the technique of multielectrode mapping (256 electrodes) developed in animal models has been extended to humans, enabling mapping of activation and repolarisation on the entire left and right ventricular epicardium in patients during cardiac surgery. Studies have examined the issue of whether ventricular fibrillation was driven by a "mother" rotor with inhomogeneous and fragmented conduction as in some animal models, or by multiple wavelets as in other animal studies; results showed that both mechanisms are operative in humans. The simpler spatial organisation of human VF has important implications for treatment and prevention. To link in-vivo human electrophysiological mapping with cellular biophysics, multielectrode mapping is now being combined with myocardial biopsies. This technique enables region-specific electrophysiology changes to be related to underlying cellular biology, for example: APD alternans, which is a precursor of VF and sudden death. The mechanism is incompletely understood but related

  6. Service and business model for technology enabled and home-based cardiac rehabilitation programs.

    Science.gov (United States)

    Sarela, Antti; Whittaker, Frank; Korhonen, Ilkka

    2009-01-01

    Cardiac rehabilitation programs are comprehensive life-style programs aimed at preventing recurrence of a cardiac event. However, the current programs have globally significantly low levels of uptake. Home-based model can be a viable alternative to hospital-based programs. We developed and analysed a service and business model for home based cardiac rehabilitation based on personal mentoring using mobile phones and web services. We analysed the different organizational and economical aspects of setting up and running the home based program and propose a potential business model for a sustainable and viable service. The model can be extended to management of other chronic conditions to enable transition from hospital and care centre based treatments to sustainable home-based care.

  7. Drosophila in the Heart of Understanding Cardiac Diseases: Modeling Channelopathies and Cardiomyopathies in the Fruitfly

    Directory of Open Access Journals (Sweden)

    Ouarda Taghli-Lamallem

    2016-02-01

    Full Text Available Cardiovascular diseases and, among them, channelopathies and cardiomyopathies are a major cause of death worldwide. The molecular and genetic defects underlying these cardiac disorders are complex, leading to a large range of structural and functional heart phenotypes. Identification of molecular and functional mechanisms disrupted by mutations causing channelopathies and cardiomyopathies is essential to understanding the link between an altered gene and clinical phenotype. The development of animal models has been proven to be efficient for functional studies in channelopathies and cardiomyopathies. In particular, the Drosophila model has been largely applied for deciphering the molecular and cellular pathways affected in these inherited cardiac disorders and for identifying their genetic modifiers. Here we review the utility and the main contributions of the fruitfly models for the better understanding of channelopathies and cardiomyopathies. We also discuss the investigated pathological mechanisms and the discoveries of evolutionarily conserved pathways which reinforce the value of Drosophila in modeling human cardiac diseases.

  8. Application of Linear Mixed-Effects Models in Human Neuroscience Research: A Comparison with Pearson Correlation in Two Auditory Electrophysiology Studies.

    Science.gov (United States)

    Koerner, Tess K; Zhang, Yang

    2017-02-27

    Neurophysiological studies are often designed to examine relationships between measures from different testing conditions, time points, or analysis techniques within the same group of participants. Appropriate statistical techniques that can take into account repeated measures and multivariate predictor variables are integral and essential to successful data analysis and interpretation. This work implements and compares conventional Pearson correlations and linear mixed-effects (LME) regression models using data from two recently published auditory electrophysiology studies. For the specific research questions in both studies, the Pearson correlation test is inappropriate for determining strengths between the behavioral responses for speech-in-noise recognition and the multiple neurophysiological measures as the neural responses across listening conditions were simply treated as independent measures. In contrast, the LME models allow a systematic approach to incorporate both fixed-effect and random-effect terms to deal with the categorical grouping factor of listening conditions, between-subject baseline differences in the multiple measures, and the correlational structure among the predictor variables. Together, the comparative data demonstrate the advantages as well as the necessity to apply mixed-effects models to properly account for the built-in relationships among the multiple predictor variables, which has important implications for proper statistical modeling and interpretation of human behavior in terms of neural correlates and biomarkers.

  9. Na/K pump regulation of cardiac repolarization: insights from a systems biology approach

    KAUST Repository

    Bueno-Orovio, Alfonso

    2013-05-15

    The sodium-potassium pump is widely recognized as the principal mechanism for active ion transport across the cellular membrane of cardiac tissue, being responsible for the creation and maintenance of the transarcolemmal sodium and potassium gradients, crucial for cardiac cell electrophysiology. Importantly, sodium-potassium pump activity is impaired in a number of major diseased conditions, including ischemia and heart failure. However, its subtle ways of action on cardiac electrophysiology, both directly through its electrogenic nature and indirectly via the regulation of cell homeostasis, make it hard to predict the electrophysiological consequences of reduced sodium-potassium pump activity in cardiac repolarization. In this review, we discuss how recent studies adopting the systems biology approach, through the integration of experimental and modeling methodologies, have identified the sodium-potassium pump as one of the most important ionic mechanisms in regulating key properties of cardiac repolarization and its rate dependence, from subcellular to whole organ levels. These include the role of the pump in the biphasic modulation of cellular repolarization and refractoriness, the rate control of intracellular sodium and calcium dynamics and therefore of the adaptation of repolarization to changes in heart rate, as well as its importance in regulating pro-arrhythmic substrates through modulation of dispersion of repolarization and restitution. Theoretical findings are consistent across a variety of cell types and species including human, and widely in agreement with experimental findings. The novel insights and hypotheses on the role of the pump in cardiac electrophysiology obtained through this integrative approach could eventually lead to novel therapeutic and diagnostic strategies. © 2013 Springer-Verlag Berlin Heidelberg.

  10. Dual optical recordings for action potentials and calcium handling in induced pluripotent stem cell models of cardiac arrhythmias using genetically encoded fluorescent indicators.

    Science.gov (United States)

    Song, LouJin; Awari, Daniel W; Han, Elizabeth Y; Uche-Anya, Eugenia; Park, Seon-Hye E; Yabe, Yoko A; Chung, Wendy K; Yazawa, Masayuki

    2015-05-01

    Reprogramming of human somatic cells to pluripotency has been used to investigate disease mechanisms and to identify potential therapeutics. However, the methods used for reprogramming, in vitro differentiation, and phenotyping are still complicated, expensive, and time-consuming. To address the limitations, we first optimized a protocol for reprogramming of human fibroblasts and keratinocytes into pluripotency using single lipofection and the episomal vectors in a 24-well plate format. This method allowed us to generate multiple lines of integration-free and feeder-free induced pluripotent stem cells (iPSCs) from seven patients with cardiac diseases and three controls. Second, we differentiated human iPSCs derived from patients with Timothy syndrome into cardiomyocytes using a monolayer differentiation method. We found that Timothy syndrome cardiomyocytes showed slower, irregular contractions and abnormal calcium handling compared with the controls. The results are consistent with previous reports using a retroviral method for reprogramming and an embryoid body-based method for cardiac differentiation. Third, we developed an efficient approach for recording the action potentials and calcium transients simultaneously in control and patient cardiomyocytes using genetically encoded fluorescent indicators, ArcLight and R-GECO1. The dual optical recordings enabled us to observe prolonged action potentials and abnormal calcium handling in Timothy syndrome cardiomyocytes. We confirmed that roscovitine rescued the phenotypes in Timothy syndrome cardiomyocytes and that these findings were consistent with previous studies using conventional electrophysiological recordings and calcium imaging with dyes. The approaches using our optimized methods and dual optical recordings will improve iPSC applicability for disease modeling to investigate mechanisms underlying cardiac arrhythmias and to test potential therapeutics.

  11. Anesthesia and Databases: Pediatric Cardiac Disease as a Role Model.

    Science.gov (United States)

    Vener, David F; Pasquali, Sara K; Mossad, Emad B

    2017-02-01

    Large data sets have now become ubiquitous in clinical medicine; they are particularly useful in high-acuity, low-volume conditions such as congenital heart disease where data must be collected from many centers. These data fall into 2 categories: administrative data arising from hospital admissions and charges and clinical data relating to specific diseases or procedures. In congenital cardiac diseases, there are now over a dozen of these data sets or registries focusing on various elements of patient care. Using probabilistic statistic matching, it is possible to marry administrative and clinical data post hoc using common elements to determine valuable information about care patterns, outcomes, and costs. These data sets can also be used in a collaborative fashion between institutions to drive quality improvement (QI). Because these data may include protected health information (PHI), care must be taken to adhere to federal guidelines on their use. A fundamental principle of large data management is the use of a common language and definition (nomenclature) to be effective. In addition, research derived from these information sources must be appropriately balanced to ensure that risk adjustments for preoperative and surgical factors are taken into consideration during the analysis. Care of patients with cardiac disease both in the United States and abroad consistently shows wide variability in mortality, morbidity, and costs, and there has been a tremendous amount of discussion about the benefits of regionalization of care based on center volume and outcome measurements. In the absence of regionalization, collaborative learning techniques have consistently been shown to minimize this variability and improve care at all centers, but before changes can be made it is necessary to accurately measure accurately current patient outcomes. Outcomes measurement generally falls under hospital-based QI initiatives, but more detailed analysis and research require

  12. When the clock strikes: Modeling the relation between circadian rhythms and cardiac arrhythmias

    Science.gov (United States)

    Seenivasan, Pavithraa; Menon, Shakti N.; Sridhar, S.; Sinha, Sitabhra

    2016-10-01

    It has recently been observed that the occurrence of sudden cardiac death has a close statistical relationship with the time of day, viz., ventricular fibrillation is most likely to occur between 12am-6am, with 6pm-12am being the next most likely period. Consequently there has been significant interest in understanding how cardiac activity is influenced by the circadian clock, i.e., temporal oscillations in physiological activity with a period close to 24 hours and synchronized with the day-night cycle. Although studies have identified the genetic basis of circadian rhythm at the intracellular level, the mechanisms by which they influence cardiac pathologies are not yet fully understood. Evidence has suggested that diurnal variations in the conductance properties of ion channel proteins that govern the excitation dynamics of cardiac cells may provide the crucial link. In this paper, we investigate the relationship between the circadian rhythm as manifested in modulations of ion channel properties and the susceptibility to cardiac arrhythmias by using a mathematical model that describes the electrical activity in ventricular tissue. We show that changes in the channel conductance that lead to extreme values for the duration of action potentials in cardiac cells can result either in abnormally high-frequency reentrant activity or spontaneous conduction block of excitation waves. Both phenomena increase the likelihood of wavebreaks that are known to initiate potentially life- threatening arrhythmias. Thus, disruptive cardiac excitation dynamics are most likely to occur in time-intervals of the day-night cycle during which the channel properties are closest to these extreme values, providing an intriguing relation between circadian rhythms and cardiac pathologies.

  13. Comparison and clinical suitability of eight prediction models for cardiac surgery-related acute kidney injury

    NARCIS (Netherlands)

    Kiers, H.D.; Boogaard, M.H.W.A. van den; Schoenmakers, M.C.J.; Hoeven, J.G. van der; Swieten, H.A. van; Heemskerk, S.; Pickkers, P.

    2013-01-01

    BACKGROUND: Cardiac surgery-related acute kidney injury (CS-AKI) results in increased morbidity and mortality. Different models have been developed to identify patients at risk of CS-AKI. While models that predict dialysis and CS-AKI defined by the RIFLE criteria are available, their predictive powe

  14. Development and Validation of Predictive Models of Cardiac Mortality and Transplantation in Resynchronization Therapy

    Directory of Open Access Journals (Sweden)

    Eduardo Arrais Rocha

    2015-01-01

    Full Text Available Abstract Background: 30-40% of cardiac resynchronization therapy cases do not achieve favorable outcomes. Objective: This study aimed to develop predictive models for the combined endpoint of cardiac death and transplantation (Tx at different stages of cardiac resynchronization therapy (CRT. Methods: Prospective observational study of 116 patients aged 64.8 ± 11.1 years, 68.1% of whom had functional class (FC III and 31.9% had ambulatory class IV. Clinical, electrocardiographic and echocardiographic variables were assessed by using Cox regression and Kaplan-Meier curves. Results: The cardiac mortality/Tx rate was 16.3% during the follow-up period of 34.0 ± 17.9 months. Prior to implantation, right ventricular dysfunction (RVD, ejection fraction < 25% and use of high doses of diuretics (HDD increased the risk of cardiac death and Tx by 3.9-, 4.8-, and 5.9-fold, respectively. In the first year after CRT, RVD, HDD and hospitalization due to congestive heart failure increased the risk of death at hazard ratios of 3.5, 5.3, and 12.5, respectively. In the second year after CRT, RVD and FC III/IV were significant risk factors of mortality in the multivariate Cox model. The accuracy rates of the models were 84.6% at preimplantation, 93% in the first year after CRT, and 90.5% in the second year after CRT. The models were validated by bootstrapping. Conclusion: We developed predictive models of cardiac death and Tx at different stages of CRT based on the analysis of simple and easily obtainable clinical and echocardiographic variables. The models showed good accuracy and adjustment, were validated internally, and are useful in the selection, monitoring and counseling of patients indicated for CRT.

  15. Electrophysiological properties of mouse and epitope-tagged human cardiac sodium channel Nav1.5 expressed in HEK293 cells [v2; ref status: indexed, http://f1000r.es/10d

    Directory of Open Access Journals (Sweden)

    Katja Reinhard

    2013-04-01

    Full Text Available Background: The pore-forming subunit of the cardiac sodium channel, Nav1.5, has been previously found to be mutated in genetically determined arrhythmias. Nav1.5 associates with many proteins that regulate its function and cellular localisation. In order to identify more in situ Nav1.5 interacting proteins, genetically-modified mice with a high-affinity epitope in the sequence of Nav1.5 can be generated. Methods: In this short study, we (1 compared the biophysical properties of the sodium current (INa generated by the mouse Nav1.5 (mNav1.5 and human Nav1.5 (hNav1.5 constructs that were expressed in HEK293 cells, and (2 investigated the possible alterations of the biophysical properties of the human Nav1.5 construct that was modified with specific epitopes. Results: The biophysical properties of mNav1.5 were similar to the human homolog. Addition of epitopes either up-stream of the N-terminus of hNav1.5 or in the extracellular loop between the S5 and S6 transmembrane segments of domain 1, significantly decreased the amount of INa and slightly altered its biophysical properties. Adding green fluorescent protein (GFP to the N-terminus did not modify any of the measured biophysical properties of hNav1.5. Conclusions: These findings have to be taken into account when planning to generate genetically-modified mouse models that harbour specific epitopes in the gene encoding mNav1.5.

  16. Pluripotent Stem Cell-Based Platforms in Cardiac Disease Modeling and Drug Testing.

    Science.gov (United States)

    Shaheen, N; Shiti, A; Gepstein, L

    2017-08-01

    The ability to generate patient/disease-specific human pluripotent stem cell (hPSC)-derived cardiomyocytes (hPSC-CMs) brings a unique value to the fields of cardiac disease modeling, drug testing, drug discovery, and precision medicine. Further integration of emerging innovative technologies such as developmental-biology inspired differentiation into chamber-specific cardiomyocyte subtypes, genome-editing, tissue-engineering, and novel functional phenotyping methodologies should facilitate even more advanced investigations. Here, we review cornerstone concepts and recent highlights of hPSC-based cardiac disease modeling and drug testing. © 2017 American Society for Clinical Pharmacology and Therapeutics.

  17. Multiphysics and multiscale modelling, data–model fusion and integration of organ physiology in the clinic: ventricular cardiac mechanics

    Science.gov (United States)

    Chabiniok, Radomir; Wang, Vicky Y.; Hadjicharalambous, Myrianthi; Asner, Liya; Lee, Jack; Sermesant, Maxime; Kuhl, Ellen; Young, Alistair A.; Moireau, Philippe; Nash, Martyn P.; Chapelle, Dominique

    2016-01-01

    With heart and cardiovascular diseases continually challenging healthcare systems worldwide, translating basic research on cardiac (patho)physiology into clinical care is essential. Exacerbating this already extensive challenge is the complexity of the heart, relying on its hierarchical structure and function to maintain cardiovascular flow. Computational modelling has been proposed and actively pursued as a tool for accelerating research and translation. Allowing exploration of the relationships between physics, multiscale mechanisms and function, computational modelling provides a platform for improving our understanding of the heart. Further integration of experimental and clinical data through data assimilation and parameter estimation techniques is bringing computational models closer to use in routine clinical practice. This article reviews developments in computational cardiac modelling and how their integration with medical imaging data is providing new pathways for translational cardiac modelling. PMID:27051509

  18. Cardiac applications of optogenetics.

    Science.gov (United States)

    Ambrosi, Christina M; Klimas, Aleksandra; Yu, Jinzhu; Entcheva, Emilia

    2014-08-01

    In complex multicellular systems, such as the brain or the heart, the ability to selectively perturb and observe the response of individual components at the cellular level and with millisecond resolution in time, is essential for mechanistic understanding of function. Optogenetics uses genetic encoding of light sensitivity (by the expression of microbial opsins) to provide such capabilities for manipulation, recording, and control by light with cell specificity and high spatiotemporal resolution. As an optical approach, it is inherently scalable for remote and parallel interrogation of biological function at the tissue level; with implantable miniaturized devices, the technique is uniquely suitable for in vivo tracking of function, as illustrated by numerous applications in the brain. Its expansion into the cardiac area has been slow. Here, using examples from published research and original data, we focus on optogenetics applications to cardiac electrophysiology, specifically dealing with the ability to manipulate membrane voltage by light with implications for cardiac pacing, cardioversion, cell communication, and arrhythmia research, in general. We discuss gene and cell delivery methods of inscribing light sensitivity in cardiac tissue, functionality of the light-sensitive ion channels within different types of cardiac cells, utility in probing electrical coupling between different cell types, approaches and design solutions to all-optical electrophysiology by the combination of optogenetic sensors and actuators, and specific challenges in moving towards in vivo cardiac optogenetics.

  19. Bifurcations in a nonlinear model of the baroreceptor-cardiac reflex

    Science.gov (United States)

    Seidel, H.; Herzel, H.

    1998-04-01

    We investigate the dynamic properties of a nonlinear model of the human cardio-baroreceptor control loop. As a new feature we use a phase effectiveness curve to describe the experimentally well-known phase dependency of the cardiac pacemaker's sensitivity to neural activity. We show that an increase of sympathetic time delays leads via a Hopf bifurcation to sustained heart rate oscillations. For increasing baroreflex sensitivity or for repetitive vagal stimulation we observe period-doubling, toroidal oscillations, chaos, and entrainment between the rhythms of the heart and the control loop. The bifurcations depend crucially on the involvement of the cardiac pacemaker's phase dependency. We compare the model output with experimental data from electrically stimulated anesthetized dogs and discuss possible implications for cardiac arrhythmias.

  20. Simulation of Cardiac Arrhythmias Using a 2D Heterogeneous Whole Heart Model.

    Science.gov (United States)

    Balakrishnan, Minimol; Chakravarthy, V Srinivasa; Guhathakurta, Soma

    2015-01-01

    Simulation studies of cardiac arrhythmias at the whole heart level with electrocardiogram (ECG) gives an understanding of how the underlying cell and tissue level changes manifest as rhythm disturbances in the ECG. We present a 2D whole heart model (WHM2D) which can accommodate variations at the cellular level and can generate the ECG waveform. It is shown that, by varying cellular-level parameters like the gap junction conductance (GJC), excitability, action potential duration (APD) and frequency of oscillations of the auto-rhythmic cell in WHM2D a large variety of cardiac arrhythmias can be generated including sinus tachycardia, sinus bradycardia, sinus arrhythmia, sinus pause, junctional rhythm, Wolf Parkinson White syndrome and all types of AV conduction blocks. WHM2D includes key components of the electrical conduction system of the heart like the SA (Sino atrial) node cells, fast conducting intranodal pathways, slow conducting atriovenctricular (AV) node, bundle of His cells, Purkinje network, atrial, and ventricular myocardial cells. SA nodal cells, AV nodal cells, bundle of His cells, and Purkinje cells are represented by the Fitzhugh-Nagumo (FN) model which is a reduced model of the Hodgkin-Huxley neuron model. The atrial and ventricular myocardial cells are modeled by the Aliev-Panfilov (AP) two-variable model proposed for cardiac excitation. WHM2D can prove to be a valuable clinical tool for understanding cardiac arrhythmias.

  1. Genetic Dissection of Cardiac Remodeling in an Isoproterenol-Induced Heart Failure Mouse Model.

    Directory of Open Access Journals (Sweden)

    Jessica Jen-Chu Wang

    2016-07-01

    Full Text Available We aimed to understand the genetic control of cardiac remodeling using an isoproterenol-induced heart failure model in mice, which allowed control of confounding factors in an experimental setting. We characterized the changes in cardiac structure and function in response to chronic isoproterenol infusion using echocardiography in a panel of 104 inbred mouse strains. We showed that cardiac structure and function, whether under normal or stress conditions, has a strong genetic component, with heritability estimates of left ventricular mass between 61% and 81%. Association analyses of cardiac remodeling traits, corrected for population structure, body size and heart rate, revealed 17 genome-wide significant loci, including several loci containing previously implicated genes. Cardiac tissue gene expression profiling, expression quantitative trait loci, expression-phenotype correlation, and coding sequence variation analyses were performed to prioritize candidate genes and to generate hypotheses for downstream mechanistic studies. Using this approach, we have validated a novel gene, Myh14, as a negative regulator of ISO-induced left ventricular mass hypertrophy in an in vivo mouse model and demonstrated the up-regulation of immediate early gene Myc, fetal gene Nppb, and fibrosis gene Lgals3 in ISO-treated Myh14 deficient hearts compared to controls.

  2. Renal and cardiac neuropeptide Y and NPY receptors in a rat model of congestive heart failure.

    Science.gov (United States)

    Callanan, Ean Y; Lee, Edward W; Tilan, Jason U; Winaver, Joseph; Haramati, Aviad; Mulroney, Susan E; Zukowska, Zofia

    2007-12-01

    Neuropeptide Y (NPY) is coreleased with norepinephrine and stimulates vasoconstriction, vascular and cardiomyocyte hypertrophy via Y1 receptors (R) and angiogenesis via Y2R. Although circulating NPY is elevated in heart failure, NPY's role remains unclear. Activation of the NPY system was determined in Wistar rats with the aortocaval (A-V) fistula model of high-output heart failure. Plasma NPY levels were elevated in A-V fistula animals (115.7 +/- 15.3 vs. 63.1 +/- 17.4 pM in sham, P renal failure (urinary Na(+) excretion renal blood flow (RBF), and death within 5-7 days (DECOMP). Cardiac and renal tissue NPY decreased with heart failure, proportionate to the severity of renal complications. Cardiac and renal Y1R mRNA expression also decreased (1.5-fold, P failure. In contrast, Y2R expression increased up to 72-fold in the heart and 5.7-fold in the kidney (P failure and cardiac hypertrophy. Changes in receptor expression were confirmed since the Y1R agonist, [Leu31, Pro34]-NPY, had no effect on RBF, whereas the Y2R agonist (13-36)-NPY increased RBF to compensate for disease. Thus, in this model of heart failure, cardiac and renal NPY Y1 receptors decrease and Y2 receptors increase, suggesting an increased effect of NPY on the receptors involved in cardiac remodeling and angiogenesis, and highlighting an important regulatory role of NPY in congestive heart failure.

  3. Neural Correlates of Consciousness at Near-Electrocerebral Silence in an Asphyxial Cardiac Arrest Model.

    Science.gov (United States)

    Lee, Donald E; Lee, Lauren G; Siu, Danny; Bazrafkan, Afsheen K; Farahabadi, Maryam H; Dinh, Tin J; Orellana, Josue; Xiong, Wei; Lopour, Beth A; Akbari, Yama

    2017-04-01

    Recent electrophysiological studies have suggested surges in electrical correlates of consciousness (i.e., elevated gamma power and connectivity) after cardiac arrest (CA). This study examines electrocorticogram (ECoG) activity and coherence of the dying brain during asphyxial CA. Male Wistar rats (n = 16) were induced with isoflurane anesthesia, which was washed out before asphyxial CA. Mean phase coherence and ECoG power were compared during different stages of the asphyxial period to assess potential neural correlates of consciousness. After asphyxia, the ECoG progressed through four distinct stages (asphyxial stages 1-4 [AS1-4]), including a transient period of near-electrocerebral silence lasting several seconds (AS3). Electrocerebral silence (AS4) occurred within 1 min of the start of asphyxia, and pulseless electrical activity followed the start of AS4 by 1-2 min. AS3 was linked to a significant increase in frontal coherence between the left and right motor cortices (p silence contains distinctive neural activity. Specifically, the burst in frontal coherence and posterior shift of ECoG power that we find during this period immediately preceding CA may be a neural correlate of conscious processing.

  4. Admission Laboratory Results to Enhance Prediction Models of Postdischarge Outcomes in Cardiac Care.

    Science.gov (United States)

    Pine, Michael; Fry, Donald E; Hannan, Edward L; Naessens, James M; Whitman, Kay; Reband, Agnes; Qian, Feng; Schindler, Joseph; Sonneborn, Mark; Roland, Jaclyn; Hyde, Linda; Dennison, Barbara A

    Predictive modeling for postdischarge outcomes of inpatient care has been suboptimal. This study evaluated whether admission numerical laboratory data added to administrative models from New York and Minnesota hospitals would enhance the prediction accuracy for 90-day postdischarge deaths without readmission (PD-90) and 90-day readmissions (RA-90) following inpatient care for cardiac patients. Risk-adjustment models for the prediction of PD-90 and RA-90 were designed for acute myocardial infarction, percutaneous cardiac intervention, coronary artery bypass grafting, and congestive heart failure. Models were derived from hospital claims data and were then enhanced with admission laboratory predictive results. Case-level discrimination, goodness of fit, and calibration were used to compare administrative models (ADM) and laboratory predictive models (LAB). LAB models for the prediction of PD-90 were modestly enhanced over ADM, but negligible benefit was seen for RA-90. A consistent predictor of PD-90 and RA-90 was prolonged length of stay outliers from the index hospitalization.

  5. A coarse-grained model to study calcium activation of the cardiac thin filament

    Science.gov (United States)

    Zhang, Jing; Schwartz, Steven

    2015-03-01

    Familial hypertrophic cardiomyopathy (FHC) is one of the most common heart disease caused by genetic mutations. Cardiac muscle contraction and relaxation involve regulation of crossbridge binding to the cardiac thin filament, which regulates actomyosin interactions through calcium-dependent alterations in the dynamics of cardiac troponin (cTn) and tropomyosin (Tm). An atomistic model of cTn complex interacting with Tm has been studied by our group. A more realistic model requires the inclusion of the dynamics of actin filament, which is almost 6 times larger than cTn and Tm in terms of atom numbers, and extensive sampling of the model becomes very resource-demanding. By using physics-based protein united-residue force field, we introduce a coarse-grained model to study the calcium activation of the thin filament resulting from cTn's allosteric regulation of Tm dynamics on actin. The time scale is much longer than that of all-atom molecular dynamics simulation because of the reduction of the degrees of freedom. The coarse-grained model is a good template for studying cardiac thin filament mutations that cause FHC, and reduces the cost of computational resources.

  6. Sodium restriction modulates innate immunity and prevents cardiac remodeling in a rat model of metabolic syndrome.

    Science.gov (United States)

    Jover, Bernard; Reynes, Christelle; Rugale, Caroline; Reboul, Cyril; Jeanson, Laura; Tournier, Michel; Lajoix, Anne Dominique; Desmetz, Caroline

    2017-02-27

    In the view of the relationships between excessive sodium intake, immunity and target organ damage, we hypothesized that reduction in dietary sodium would be beneficial in the prevention of cardiac alterations through a restrained local immunity response in a rat model of metabolic syndrome. Sprague-Dawley rats were fed a 60% fructose diet with either a normal sodium (0.64% NaCl) or a low sodium content (<0.01% NaCl) for 8weeks. After 4weeks, rats were infused or not with angiotensin II (200ng.kg(-1).min(-1), sc) for 4weeks. Tail-cuff blood pressure was determined in conscious rats. Heart and left ventricle weight, cardiomyocyte size, and cardiac fibrosis were evaluated. We performed a transcriptomic analysis in order to identify differentially regulated cardiac mRNAs between normal and low sodium diets. We validated those results using qPCR and immunohistochemistry. Angiotensin II-induced blood pressure rise was blunted (~ 50%) in the low-sodium fed rats while cardiac hypertrophy and fibrosis were prevented. Transcriptomic analysis revealed 66 differentially regulated genes including 13 downregulated genes under the low sodium diet and implicated in the innate immune response. This was confirmed by reduced cardiac macrophages infiltration under the low sodium diet. Dietary sodium restriction prevents structural alterations of the heart of rats with fructose-induced insulin resistance and angiotensin II-hypertension. The reduction of cardiac inflammation and macrophage infiltration suggests that innate immunity has an important role in the beneficial effect of sodium restriction on cardiac remodeling.

  7. Pioglitazone attenuates cardiac fibrosis and hypertrophy in a rat model of diabetic nephropathy.

    Science.gov (United States)

    Elrashidy, Rania A; Asker, Mervat E; Mohamed, Hoda E

    2012-09-01

    Pioglitazone has been demonstrated to have beneficial effects on cardiovascular outcomes. However, little is known about its effect on cardiac remodeling associated with diabetic nephropathy. Therefore, this study was designed to study the effects of pioglitazone on cardiac fibrosis and hypertrophy in a rat model of diabetic nephropathy. For this purpose, male Wistar albino rats were randomly assigned into 4 groups (n = 10 per group): normal (N) group, diabetic (D) group, diabetic nephropathic (DN) group received an equal amount of vehicle (0.5% carboxy methyl cellulose), and diabetic nephropathic group treated by oral administration of pioglitazone (10 mg/kg per d) for 4 weeks. Diabetic nephropathy was induced by subtotal nephrectomy plus streptozotocin (STZ) injection. The results revealed that DN rats showed excessive deposition of collagen fibers in their cardiac tissue, along with a marked myocyte hypertrophy. This was associated with a dramatic upregulation of cardiac transforming growth factor-β1 (TGF-β1) gene. Furthermore, the gene expression of matrix metalloproteinase 2 (MMP-2) decreased, while the gene expression of tissue inhibitor of metalloproteinase 2 (TIMP-2) increased in the hearts of DN rats. In addition, enhanced lipid peroxidation and myocardial injury, evidenced by a significant increase in their serum creatine kinase-MB level were observed in DN rats. All these abnormalities were ameliorated by pioglitazone administration. Our findings suggest that upregulation of cardiac TGF-β1 gene along with the imbalance between MMP-2 and TIMP-2 expressions is critically involved in cardiac fibrosis associated with diabetic nephropathy. Pioglitazone can ameliorate cardiac remodeling by suppressing the gene expression of TGF-β1 and regulating the MMP-2/TIMP-2 system.

  8. Effect of impaired glucose tolerance on cardiac dysfunction in a rat model of prediabetes

    Institute of Scientific and Technical Information of China (English)

    LIANG Jia-liang; FENG Zhi-kuan; LIU Xiao-ying; LIN Qiu-xiong; FU Yong-heng; SHAN Zhi-xin; ZHU Jie-ning; LIN Shu-guang; YU Xi-yong

    2011-01-01

    Background The effect of impaired glucose tolerance (IGT) on cardiac function during the chronic prediabetes state is complicated and plays an important role in clinical outcome. However, the molecular mechanisms are not fully understood. This study was designed to observe cardiac dysfunction in prediabetic rats with IGT and to determine whether glucose metabolic abnormalities, inflammation and apoptosis are linked to it.Methods The IGT rat models were induced by streptozocin, and the heart functions were assessed by echocardiography.Myocardial glucose metabolism was analyzed by glycogen periodic acid-Schiff staining, and the pro-apoptotic effect of IGT was evaluated by TUNEL staining. Additionally, caspase-3 activation, macrophage migration inhibitory factor (MIF) and G-protein coupled receptor kinase 2 (GRK2) were detected by Western blotting in cardiac tissue lysates.Results Area-under-the-curve of blood glucose in rats injected with streptozotocin was higher than that in controls,increased by 16.28%, 38.60% and 38.61% at 2, 4 and 6 weeks respectively (F=15.370, P=0.003). Abnormal cardiac functions and apoptotic cardiomyocytes were observed in the IGT rats, the ejection fraction (EF) being (68.59±6.62)% in IGT rats vs. (81.07±4.59)% in controls (t=4.020, P=0.002). There was more glucose which was converted to glycogen in the myocardial tissues of IGT rats, especially in cardiac perivascular tissues. Compared to controls, the cleaved caspase-3, MIF and GRK2 were expressed at higher levels in the myocardial tissues of IGT rats.Conclusions IGT in the prediabetes period resulted in cardiac dysfunction linked to abnormal glycogen storage and apoptosis. Additionally, MIF and GRK2 may be involved in the pathogenesis of cardiac dysfunction in prediabetes and their regulation may contribute to the design of novel diagnostic and therapeutic strategies for those who have potential risks for diabetic cardiovascular complications.

  9. Improved Cuff Technique for Establishing a Mouse-Rat Heterotopic Cardiac Xenotransplantation Model.

    Science.gov (United States)

    Li, C; Qi, F; Liu, T; Wang, H; Wang, P-Z

    2015-01-01

    The small animal model of cardiac transplantation is the most common model in organ transplantation studies. The cervical heterotopic transplantation is widely performed because this allows for direct observation of the graft heartbeat and contributes to early prediction of graft rejection. A mouse-rat cervical heterotopic cardiac xenotransplantation model was modified with respect to the anesthesia method, cardiac graft harvesting method, and perioperative treatment. These improvements ensure the stability and reliability of xenotransplantation models for in vivo studies of immune-mediated graft rejection. After establishing isoflurane inhalation anesthesia, the donors' hearts were harvested. The experimental method involved separate ligation of the left and right superior venae cavae; the other blood vessels were ligated in a cluster. Both the donor and recipient animals were placed on a heating pad intraoperatively to maintain a body temperature of 37-40 °C. The model establishment was divided into 3 stages: practice, stabilization, and stereotyping. The surgical success rate and operation time were recorded. Specimens were harvested at different time points for histopathological examination. The anesthetic effect of isoflurane was well maintained, and no animals died of adverse anesthetic events. Body temperature was maintained at 37-40 °C which effectively shortened the time to restoration. The modification of the cardiac graft harvesting method is conducive to rebeating of the donor heart. The success rates in the stabilization and stereotyping stages were significantly higher than that in the practice stage (P rat cervical heterotopic cardiac xenotransplantation model is the ideal animal model for studying xenograft rejection. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. A two-variable model robust to pacemaker behaviour for the dynamics of the cardiac action potential.

    Science.gov (United States)

    Corrado, Cesare; Niederer, Steven A

    2016-11-01

    Ionic models with two state variables are routinely used in patient specific electro-physiology simulations due to the small number of parameters to be constrained and their computational tractability. Among these models, the Mitchell and Schaeffer (MS) action potential model is often used in ventricle electro-physiology due to its ability to reproduce the shape of the action potential and its restitution properties. However, for some choices of parameters characterising this ionic model, unwanted pacemaker behaviour is present. The absence of any a priori criterion to exclude unstable parameter combinations affects parameter fitting algorithms, as unphysiological solutions can only be discarded a posteriori. In this paper we propose an adaptation of the MS model that does not exhibit pacemaker behaviour for any combination of the parameters. The robustness to pacemaker behaviour makes this model suitable for inverse problem applications. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Hearing Aid Fitting & Electrophysiologic Procedure

    Directory of Open Access Journals (Sweden)

    Bahram Jalaei

    2001-05-01

    Full Text Available Rehabilitation of deaf individual is one of the important subjects that has attracted attention of many researchers during past centuries. Different opinions have been established in this direction. Electrophysiologic tests were established and developed parallel to developments in rehabilitation. Therefore, opinion of using electrophysiologic test for evaluation and fitting of hearing aid became gradually popular. Ultimately, the electrophysiologic tests are used in evaluation and fitting of hearing aid in two ways: 1-Direct way 2- Indirect way "nIn direct way aided ABR is obtained and special attention is paid to wave V. This technique has many difficulties. Inindirect way, electrophysiologic tests such, ECochG, OAE and ABR, AMLR, ALR and P300 and other objective tests are used, especially in infants and neonates for evaluating the state of hearing. Researches are continuing in this field. It is probable to have aided electrophysiologic responses with speech stimuli in near future.

  12. Echocardiographic assessment of cardiac morphology and function in Xenopus.

    Science.gov (United States)

    Bartlett, Heather L; Escalera, Robert B; Patel, Sonali S; Wedemeyer, Elesa W; Volk, Kenneth A; Lohr, Jamie L; Reinking, Benjamin E

    2010-04-01

    Advances using Xenopus as a model permit valuable inquiries into cardiac development from embryo to adult. Noninvasive methods are needed to study cardiac function longitudinally. The objective of this study was to evaluate the feasibility of echocardiographic studies in Xenopus and establish normative data of adult cardiac structure and function. Doppler and 2D echocardiograms and electrocardiograms were acquired from adult Xenopus laevis and X. tropicalis. Frogs were exposed to either isoflurane or tricaine to discern the effect of sedating agents on cardiac function. Cardiac dimensions, morphology, flow velocities, and electrophysiologic intervals were measured and evaluated by using bivariate and regression analyses. Normal cardiac dimensions relative to body weight and species were established by echocardiography. Normal conduction intervals were determined by electrocardiography and did not vary by body weight or species. Anesthetic agent did not affect ejection fraction or flow velocity but did alter the QRS duration and QT interval. Echocardiographic and electrocardiographic studies in Xenopus provide information about cardiac anatomy and physiology and can readily be used for longitudinal analyses of developmental inquiries. Body weight, species, and anesthetic agent are factors that should be considered in experimental design and analyses.

  13. Advanced computer techniques for inverse modeling of electric current in cardiac tissue

    Energy Technology Data Exchange (ETDEWEB)

    Hutchinson, S.A.; Romero, L.A.; Diegert, C.F.

    1996-08-01

    For many years, ECG`s and vector cardiograms have been the tools of choice for non-invasive diagnosis of cardiac conduction problems, such as found in reentrant tachycardia or Wolff-Parkinson-White (WPW) syndrome. Through skillful analysis of these skin-surface measurements of cardiac generated electric currents, a physician can deduce the general location of heart conduction irregularities. Using a combination of high-fidelity geometry modeling, advanced mathematical algorithms and massively parallel computing, Sandia`s approach would provide much more accurate information and thus allow the physician to pinpoint the source of an arrhythmia or abnormal conduction pathway.

  14. Metformin improves cardiac function in a nondiabetic rat model of post-MI heart failure

    NARCIS (Netherlands)

    Yin, Meimei; van der Horst, Iwan C. C.; van Melle, Joost P.; Qian, Cheng; van Gilst, Wiek H.; Sillje, Herman H. W.; de Boer, Rudolf A.

    2011-01-01

    Yin M, van der Horst IC, van Melle JP, Qian C, van Gilst WH, Sillje HH, de Boer RA. Metformin improves cardiac function in a nondiabetic rat model of post-MI heart failure. Am J Physiol Heart Circ Physiol 301: H459-H468, 2011. First published May 13, 2011; doi:10.1152/ajpheart.00054.2011.-Metformin

  15. A model to calculate cardiac output in hemodialysis patients by thermodilution

    Directory of Open Access Journals (Sweden)

    Alayoud Ahmed

    2012-06-01

    Full Text Available Abstract The Blood Temperature Monitor module (BTM is used to measure recirculation by thermodilution in dialysis. Numerous studies have confirmed its interest in the measuring of the vascular access flow. In this letter we describe a model to calculate cardiac output in dialysis by the BTM.

  16. Human embryonic stem cells as a model for cardiac gene discovery : from chip to chap

    NARCIS (Netherlands)

    Beqqali, A.

    2008-01-01

    Here we described the use of human embryonic stem cells (hESCs) as a model to obtain insights into commitment to the mesoderm and endoderm lineages and the early steps in human cardiac cell differentiation by means of whole-genome temporal expression profiling. Furthermore, we used it as an approach

  17. Cardiovascular Imaging in the Electrophysiology Laboratory.

    Science.gov (United States)

    Sanchis, Laura; Prat, Susanna; Sitges, Marta

    2016-06-01

    In recent years, rapid technological advances have allowed the development of new electrophysiological procedures that would not have been possible without the parallel development of imaging techniques used to plan and guide these procedures and monitor their outcomes. Ablation of atrial fibrillation is among the interventions with the greatest need for imaging support. Echocardiography allows the appropriate selection of patients and the detection of thrombi that would contraindicate the intervention; cardiac magnetic resonance imaging and computed tomography are also essential in planning this procedure, by allowing a detailed anatomical study of the pulmonary veins. In addition, in cardiac resynchronization therapy, echocardiography plays a central role in both patient selection and, later, in device adjustment and in assessing the effectiveness of the technique. More recently, ablation of ventricular tachycardias has been established as a treatment option; this would not be possible without planning using an imaging study such as cardiac magnetic resonance imaging of myocardial scarring. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  18. Using a human cardiovascular-respiratory model to characterize cardiac tamponade and pulsus paradoxus

    Science.gov (United States)

    Ramachandran, Deepa; Luo, Chuan; Ma, Tony S; Clark, John W

    2009-01-01

    Background Cardiac tamponade is a condition whereby fluid accumulation in the pericardial sac surrounding the heart causes elevation and equilibration of pericardial and cardiac chamber pressures, reduced cardiac output, changes in hemodynamics, partial chamber collapse, pulsus paradoxus, and arterio-venous acid-base disparity. Our large-scale model of the human cardiovascular-respiratory system (H-CRS) is employed to study mechanisms underlying cardiac tamponade and pulsus paradoxus. The model integrates hemodynamics, whole-body gas exchange, and autonomic nervous system control to simulate pressure, volume, and blood flow. Methods We integrate a new pericardial model into our previously developed H-CRS model based on a fit to patient pressure data. Virtual experiments are designed to simulate pericardial effusion and study mechanisms of pulsus paradoxus, focusing particularly on the role of the interventricular septum. Model differential equations programmed in C are solved using a 5th-order Runge-Kutta numerical integration scheme. MATLAB is employed for waveform analysis. Results The H-CRS model simulates hemodynamic and respiratory changes associated with tamponade clinically. Our model predicts effects of effusion-generated pericardial constraint on chamber and septal mechanics, such as altered right atrial filling, delayed leftward septal motion, and prolonged left ventricular pre-ejection period, causing atrioventricular interaction and ventricular desynchronization. We demonstrate pericardial constraint to markedly accentuate normal ventricular interactions associated with respiratory effort, which we show to be the distinct mechanisms of pulsus paradoxus, namely, series and parallel ventricular interaction. Series ventricular interaction represents respiratory variation in right ventricular stroke volume carried over to the left ventricle via the pulmonary vasculature, whereas parallel interaction (via the septum and pericardium) is a result of

  19. Cannabinoid and nitric oxide signaling interplay in the modulation of hippocampal hyperexcitability: Study on electrophysiological and behavioral models of temporal lobe epilepsy in the rat.

    Science.gov (United States)

    Carletti, F; Gambino, G; Rizzo, V; Ferraro, G; Sardo, P

    2015-09-10

    A growing bulk of evidence suggests that cannabinoid system plays a pivotal role in the control of hyperexcitability phenomena. Notwithstanding, the anticonvulsant action of cannabinoids has not been fully addressed, in particular the involvement of potential cellular neuromodulators, for instance nitric oxide. In the current study, we focused on two distinct rat models of temporal lobe epilepsy, the Maximal Dentate Activation and the pilocarpine-induced acute seizures, providing both electrophysiological and behavioral data on cannabinoid and nitrergic system interplay. We evaluated the antiepileptic effects of WIN 55,212-2, (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl) pyrrolo[1,2,3-de]-1,4-benzoxazin-6-Yl]-1-naphthalenylmethanone (WIN), a CB agonist, and of 7-Nitroindazole (7NI), a preferential neuronal nitric oxide synthase (nNOS) inhibitor, at different doses, alone and in combination. MDA study showed that these drugs protected animals in a dose-dependent manner from electrically induced epileptiform discharges. In pilocarpine model, a dose-related activity of 7NI and WIN: a) decreased the behavioral scoring, used to describe the severity of chemically induced acute seizures; b) affected latency of the onset of acute convulsions; c) dampened mortality rate. Interestingly, the combination of the treatments brought to light that individually ineffective doses of WIN turn into effective when nNOS activity is pharmacologically inhibited in both experimental conditions. This effect is mediated by CB1 receptor since the co-administration of N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251), a CB1 receptor specific antagonist, thwarted the 7NI-WIN convergent action. In the light of this, our findings suggest a putative antagonism between CBr-activated pathway and NO signaling in the context of neuronal hyperexcitability and contribute to elucidate possible synaptic processes underlying neuroprotective

  20. Antiepileptic effect of fisetin in iron-induced experimental model of traumatic epilepsy in rats in the light of electrophysiological, biochemical, and behavioral observations.

    Science.gov (United States)

    Das, Jharana; Singh, Rameshwar; Sharma, Deepak

    2017-05-01

    Traumatic epilepsy is defined by episodes of recurring seizures secondary to severe brain injury. Though drugs are found effective to control seizures, their long-term use have been observed to increase reactive oxygen species in animals. Flavonoid fisetin, a natural bioactive phytonutrient reported to exert anticonvulsive effect in experimental seizure models. But, trauma-induced seizures could not be prevented by anticonvulsants was reported in some clinical studies. To study the effect of fisetin on epileptiform electrographic activity in iron-induced traumatic epilepsy and also the probable reason behind the effect in rats. Fisetin pretreatment (20 mg/kg body wt., p.o.) of rats for 12 weeks were chosen followed by injecting iron (5 µl, 100 mM) stereotaxically to generate iron-induced epilepsy. Experimental design include electrophysiological study (electroencephalograph in correlation with multiple unit activity (MUA) in the cortex and CA1 subfield of the hippocampus; spectral analysis of seizure and seizure-associated behavioral study (Morris water maze for spatial learning, open-field test for anxiety) and biochemical study (lipid peroxidation, Na(+),K(+)-ATPase activity) in both the cortex and the hippocampus. Fisetin pretreatment was found to prevent the development of iron-induced electrical seizure and decrease the corresponding MUA in the cortex (*P˂0.05) as well as in the hippocampus (***P˂0.001). Fisetin pretreatment decreased the lipid peroxides (*P˂0.05) and retained the Na(+),K(+)-ATPase activity (*P˂0.05) which was found altered in the epileptic animals and also found to attenuate the seizure-associated cognitive dysfunctions. This study demonstrated the antiepileptic action of fisetin in iron-induced model of epileptic rats by inhibiting oxidative stress.

  1. Optimisation of a Generic Ionic Model of Cardiac Myocyte Electrical Activity

    Directory of Open Access Journals (Sweden)

    Tianruo Guo

    2013-01-01

    Full Text Available A generic cardiomyocyte ionic model, whose complexity lies between a simple phenomenological formulation and a biophysically detailed ionic membrane current description, is presented. The model provides a user-defined number of ionic currents, employing two-gate Hodgkin-Huxley type kinetics. Its generic nature allows accurate reconstruction of action potential waveforms recorded experimentally from a range of cardiac myocytes. Using a multiobjective optimisation approach, the generic ionic model was optimised to accurately reproduce multiple action potential waveforms recorded from central and peripheral sinoatrial nodes and right atrial and left atrial myocytes from rabbit cardiac tissue preparations, under different electrical stimulus protocols and pharmacological conditions. When fitted simultaneously to multiple datasets, the time course of several physiologically realistic ionic currents could be reconstructed. Model behaviours tend to be well identified when extra experimental information is incorporated into the optimisation.

  2. Cardiac and Skeletal Muscle Defects in a Mouse Model of Human Barth Syndrome*

    Science.gov (United States)

    Acehan, Devrim; Vaz, Frederic; Houtkooper, Riekelt H.; James, Jeanne; Moore, Vicky; Tokunaga, Chonan; Kulik, Willem; Wansapura, Janaka; Toth, Matthew J.; Strauss, Arnold; Khuchua, Zaza

    2011-01-01

    Barth syndrome is an X-linked genetic disorder caused by mutations in the tafazzin (taz) gene and characterized by dilated cardiomyopathy, exercise intolerance, chronic fatigue, delayed growth, and neutropenia. Tafazzin is a mitochondrial transacylase required for cardiolipin remodeling. Although tafazzin function has been studied in non-mammalian model organisms, mammalian genetic loss of function approaches have not been used. We examined the consequences of tafazzin knockdown on sarcomeric mitochondria and cardiac function in mice. Tafazzin knockdown resulted in a dramatic decrease of tetralinoleoyl cardiolipin in cardiac and skeletal muscles and accumulation of monolysocardiolipins and cardiolipin molecular species with aberrant acyl groups. Electron microscopy revealed pathological changes in mitochondria, myofibrils, and mitochondrion-associated membranes in skeletal and cardiac muscles. Echocardiography and magnetic resonance imaging revealed severe cardiac abnormalities, including left ventricular dilation, left ventricular mass reduction, and depression of fractional shortening and ejection fraction in tafazzin-deficient mice. Tafazzin knockdown mice provide the first mammalian model system for Barth syndrome in which the pathophysiological relationships between altered content of mitochondrial phospholipids, ultrastructural abnormalities, myocardial and mitochondrial dysfunction, and clinical outcome can be completely investigated. PMID:21068380

  3. Epigenomic model of cardiac enhancers with application to genome wide association studies.

    Science.gov (United States)

    Sahu, Avinash Das; Aniba, Radhouane; Chang, Yen-Pei Christy; Hannenhalli, Sridhar

    2013-01-01

    Mammalian gene regulation is often mediated by distal enhancer elements, in particular, for tissue specific and developmental genes. Computational identification of enhancers is difficult because they do not exhibit clear location preference relative to their target gene and also because they lack clearly distinguishing genomic features. This represents a major challenge in deciphering transcriptional regulation. Recent ChIP-seq based genome-wide investigation of epigenomic modifications have revealed that enhancers are often enriched for certain epigenomic marks. Here we utilize the epigenomic data in human heart tissue along with validated human heart enhancers to develop a Support Vector Machine (SVM) model of cardiac enhancers. Cross-validation classification accuracy of our model was 84% and 92% on positive and negative sets respectively with ROC AUC = 0.92. More importantly, while P300 binding has been used as gold standard for enhancers, our model can distinguish P300-bound validated enhancers from other P300-bound regions that failed to exhibit enhancer activity in transgenic mouse. While GWAS studies reveal polymorphic regions associated with certain phenotypes, they do not immediately provide causality. Next, we hypothesized that genomic regions containing a GWAS SNP associated with a cardiac phenotype might contain another SNP in a cardiac enhancer, which presumably mediates the phenotype. Starting with a comprehensive set of SNPs associated with cardiac phenotypes in GWAS studies, we scored other SNPs in LD with the GWAS SNP according to its probability of being an enhancer and choose one with best score in the LD as enhancer. We found that our predicted enhancers are enriched for known cardiac transcriptional regulator motifs and are likely to regulate the nearby gene. Importantly, these tendencies are more favorable for the predicted enhancers compared with an approach that uses P300 binding as a marker of enhancer activity.

  4. Age-related changes in predictive capacity versus internal model adaptability: electrophysiological evidence that individual differences outweigh effects of age

    Directory of Open Access Journals (Sweden)

    Ina eBornkessel-Schlesewsky

    2015-11-01

    Full Text Available Hierarchical predictive coding has been identified as a possible unifying principle of brain function, and recent work in cognitive neuroscience has examined how it may be affected by age–related changes. Using language comprehension as a test case, the present study aimed to dissociate age-related changes in prediction generation versus internal model adaptation following a prediction error. Event-related brain potentials (ERPs were measured in a group of older adults (60–81 years; n=40 as they read sentences of the form The opposite of black is white/yellow/nice. Replicating previous work in young adults, results showed a target-related P300 for the expected antonym (white; an effect assumed to reflect a prediction match, and a graded N400 effect for the two incongruous conditions (i.e. a larger N400 amplitude for the incongruous continuation not related to the expected antonym, nice, versus the incongruous associated condition, yellow. These effects were followed by a late positivity, again with a larger amplitude in the incongruous non-associated versus incongruous associated condition. Analyses using linear mixed-effects models showed that the target-related P300 effect and the N400 effect for the incongruous non-associated condition were both modulated by age, thus suggesting that age-related changes affect both prediction generation and model adaptation. However, effects of age were outweighed by the interindividual variability of ERP responses, as reflected in the high proportion of variance captured by the inclusion of by-condition random slopes for participants and items. We thus argue that – at both a neurophysiological and a functional level – the notion of general differences between language processing in young and older adults may only be of limited use, and that future research should seek to better understand the causes of interindividual variability in the ERP responses of older adults and its relation to cognitive

  5. Thoracic 9 Spinal Transection-Induced Model of Muscle Spasticity in the Rat: A Systematic Electrophysiological and Histopathological Characterization.

    Directory of Open Access Journals (Sweden)

    Jose A Corleto

    Full Text Available The development of spinal hyper-reflexia as part of the spasticity syndrome represents one of the major complications associated with chronic spinal traumatic injury (SCI. The primary mechanism leading to progressive appearance of muscle spasticity is multimodal and may include loss of descending inhibitory tone, alteration of segmental interneuron-mediated inhibition and/or increased reflex activity to sensory input. Here, we characterized a chronic thoracic (Th 9 complete transection model of muscle spasticity in Sprague-Dawley (SD rats. Isoflurane-anesthetized rats received a Th9 laminectomy and the spinal cord was transected using a scalpel blade. After the transection the presence of muscle spasticity quantified as stretch and cutaneous hyper-reflexia was identified and quantified as time-dependent changes in: i ankle-rotation-evoked peripheral muscle resistance (PMR and corresponding electromyography (EMG activity, ii Hoffmann reflex, and iii EMG responses in gastrocnemius muscle after paw tactile stimulation for up to 8 months after injury. To validate the clinical relevance of this model, the treatment potency after systemic treatment with the clinically established anti-spastic agents baclofen (GABAB receptor agonist, tizanidine (α2-adrenergic agonist and NGX424 (AMPA receptor antagonist was also tested. During the first 3 months post spinal transection, a progressive increase in ankle rotation-evoked muscle resistance, Hoffmann reflex amplitude and increased EMG responses to peripherally applied tactile stimuli were consistently measured. These changes, indicative of the spasticity syndrome, then remained relatively stable for up to 8 months post injury. Systemic treatment with baclofen, tizanidine and NGX424 led to a significant but transient suppression of spinal hyper-reflexia. These data demonstrate that a chronic Th9 spinal transection model in adult SD rat represents a reliable experimental platform to be used in studying the

  6. Acute retinal ischemia caused by controlled low ocular perfusion pressure in a porcine model. Electrophysiological and histological characterisation

    DEFF Research Database (Denmark)

    Kyhn, Maria Voss; Warfvinge, Karin; Scherfig, Erik

    2009-01-01

    The purpose of this study was to establish, and characterize a porcine model of acute, controlled retinal ischemia. The controlled retinal ischemia was produced by clamping the ocular perfusion pressure (OPP) in the left eye to 5 mm Hg for 2 h. The OPP was defined as mean arterial blood pressure...... (MAP) minus the intraocular pressure (IOP). It was clamped to 0-30 mm Hg by continuous monitoring of MAP and adjustment of the IOP, which was controlled by cannulation of the anterior chamber. Inner retinal function was assessed by induced multifocal electroretinography (mfERG) with comparisons...

  7. Modeling tissue- and mutation- specific electrophysiological effects in the long QT syndrome: role of the Purkinje fiber.

    Directory of Open Access Journals (Sweden)

    Vivek Iyer

    Full Text Available Congenital long QT syndrome is a heritable family of arrhythmias caused by mutations in 13 genes encoding ion channel complex proteins. Mounting evidence has implicated the Purkinje fiber network in the genesis of ventricular arrhythmias. In this study, we explore the hypothesis that long QT mutations can demonstrate different phenotypes depending on the tissue type of expression. Using computational models of the human ventricular myocyte and the Purkinje fiber cell, the biophysical alteration in channel function in LQT1, LQT2, LQT3, and LQT7 are modeled. We identified that the plateau potential was important in LQT1 and LQT2, in which mutation led to minimal action potential prolongation in Purkinje fiber cells. The phenotype of LQT3 mutation was dependent on the biophysical alteration induced as well as tissue type. The canonical ΔKPQ mutation causes severe action potential prolongation in both tissue types. For LQT3 mutation F1473C, characterized by shifted channel availability, a more severe phenotype was seen in Purkinje fiber cells with action potential prolongation and early afterdepolarizations. The LQT3 mutation S1904L demonstrated striking effects on action potential duration restitution and more severe action potential prolongation in Purkinje fiber cells at higher heart rates. Voltage clamp simulations highlight the mechanism of effect of these mutations in different tissue types, and impact of drug therapy is explored. We conclude that arrhythmia formation in long QT syndrome may depend not only on the basis of mutation and biophysical alteration, but also upon tissue of expression. The Purkinje fiber network may represent an important therapeutic target in the management of patients with heritable channelopathies.

  8. Electrophysiological and structural remodeling in heart failure modulate arrhythmogenesis. 2D simulation study.

    Directory of Open Access Journals (Sweden)

    Juan F Gomez

    Full Text Available Heart failure is operationally defined as the inability of the heart to maintain blood flow to meet the needs of the body and it is the final common pathway of various cardiac pathologies. Electrophysiological remodeling, intercellular uncoupling and a pro-fibrotic response have been identified as major arrhythmogenic factors in heart failure.In this study we investigate vulnerability to reentry under heart failure conditions by incorporating established electrophysiological and anatomical remodeling using computer simulations.The electrical activity of human transmural ventricular tissue (5 cm × 5 cm was simulated using the human ventricular action potential model Grandi et al. under control and heart failure conditions. The MacCannell et al. model was used to model fibroblast electrical activity, and their electrotonic interactions with myocytes. Selected degrees of diffuse fibrosis and variations in intercellular coupling were considered and the vulnerable window (VW for reentry was evaluated following cross-field stimulation.No reentry was observed in normal conditions or in the presence of HF ionic remodeling. However, defined amount of fibrosis and/or cellular uncoupling were sufficient to elicit reentrant activity. Under conditions where reentry was generated, HF electrophysiological remodeling did not alter the width of the VW. However, intermediate fibrosis and cellular uncoupling significantly widened the VW. In addition, biphasic behavior was observed, as very high fibrotic content or very low tissue conductivity hampered the development of reentry. Detailed phase analysis of reentry dynamics revealed an increase of phase singularities with progressive fibrotic components.Structural remodeling is a key factor in the genesis of vulnerability to reentry. A range of intermediate levels of fibrosis and intercellular uncoupling can combine to favor reentrant activity.

  9. Chronic intermittent hypoxia induces cardiac inflammation and dysfunction in a rat obstructive sleep apnea model.

    Science.gov (United States)

    Wei, Qin; Bian, Yeping; Yu, Fuchao; Zhang, Qiang; Zhang, Guanghao; Li, Yang; Song, Songsong; Ren, Xiaomei; Tong, Jiayi

    2016-11-01

    Chronic intermittent hypoxia is considered to play an important role in cardiovascular pathogenesis during the development of obstructive sleep apnea (OSA). We used a well-described OSA rat model induced with simultaneous intermittent hypoxia. Male Sprague Dawley rats were individually placed into plexiglass chambers with air pressure and components were electronically controlled. The rats were exposed to intermittent hypoxia 8 hours daily for 5 weeks. The changes of cardiac structure and function were examined by ultrasound. The cardiac pathology, apoptosis, and fibrosis were analyzed by H&E staining, TUNNEL assay, and picosirius staining, respectively. The expression of inflammation and fibrosis marker genes was analyzed by quantitative real-time PCR and Western blot. Chronic intermittent hypoxia/low pressure resulted in significant increase of left ventricular internal diameters (LVIDs), end-systolic volume (ESV), end-diastolic volume (EDV), and blood lactate level and marked reduction in ejection fraction and fractional shortening. Chronic intermittent hypoxia increased TUNNEL-positive myocytes, disrupted normal arrangement of cardiac fibers, and increased Sirius stained collagen fibers. The expression levels of hypoxia induced factor (HIF)-1α, NF-kB, IL-6, and matrix metallopeptidase 2 (MMP-2) were significantly increased in the heart of rats exposed to chronic intermittent hypoxia. In conclusion, the left ventricular function was adversely affected by chronic intermittent hypoxia, which is associated with increased expression of HIF-1α and NF-kB signaling molecules and development of cardiac inflammation, apoptosis and fibrosis.

  10. Blue sky catastrophe as applied to modeling of cardiac rhythms

    Science.gov (United States)

    Glyzin, S. D.; Kolesov, A. Yu.; Rozov, N. Kh.

    2015-07-01

    A new mathematical model for the electrical activity of the heart is proposed. The model represents a special singularly perturbed three-dimensional system of ordinary differential equations with one fast and two slow variables. A characteristic feature of the system is that its solution performs nonclassical relaxation oscillations and simultaneously undergoes a blue sky catastrophe bifurcation. Both these factors make it possible to achieve a phenomenological proximity between the time dependence of the fast component in the model and an ECG of the human heart.

  11. A new model to predict acute kidney injury requiring renal replacement therapy after cardiac surgery

    Science.gov (United States)

    Pannu, Neesh; Graham, Michelle; Klarenbach, Scott; Meyer, Steven; Kieser, Teresa; Hemmelgarn, Brenda; Ye, Feng; James, Matthew

    2016-01-01

    Background: Acute kidney injury after cardiac surgery is associated with adverse in-hospital and long-term outcomes. Novel risk factors for acute kidney injury have been identified, but it is unknown whether their incorporation into risk models substantially improves prediction of postoperative acute kidney injury requiring renal replacement therapy. Methods: We developed and validated a risk prediction model for acute kidney injury requiring renal replacement therapy within 14 days after cardiac surgery. We used demographic, and preoperative clinical and laboratory data from 2 independent cohorts of adults who underwent cardiac surgery (excluding transplantation) between Jan. 1, 2004, and Mar. 31, 2009. We developed the risk prediction model using multivariable logistic regression and compared it with existing models based on the C statistic, Hosmer–Lemeshow goodness-of-fit test and Net Reclassification Improvement index. Results: We identified 8 independent predictors of acute kidney injury requiring renal replacement therapy in the derivation model (adjusted odds ratio, 95% confidence interval [CI]): congestive heart failure (3.03, 2.00–4.58), Canadian Cardiovascular Society angina class III or higher (1.66, 1.15–2.40), diabetes mellitus (1.61, 1.12–2.31), baseline estimated glomerular filtration rate (0.96, 0.95–0.97), increasing hemoglobin concentration (0.85, 0.77–0.93), proteinuria (1.65, 1.07–2.54), coronary artery bypass graft (CABG) plus valve surgery (v. CABG only, 1.25, 0.64–2.43), other cardiac procedure (v. CABG only, 3.11, 2.12–4.58) and emergent status for surgery booking (4.63, 2.61–8.21). The 8-variable risk prediction model had excellent performance characteristics in the validation cohort (C statistic 0.83, 95% CI 0.79–0.86). The net reclassification improvement with the prediction model was 13.9% (p < 0.001) compared with the best existing risk prediction model (Cleveland Clinic Score). Interpretation: We have developed

  12. Prediction of cardiac arrest recurrence using ensemble classifiers

    Indian Academy of Sciences (India)

    NACHIKET TAPAS; TUSHAR LONE; DAMODAR REDDY; VENKATANARESH KUPPILI

    2017-07-01

    Inability of a heart to contract effectually or its failure to contract prevents blood from circulating efficiently, causing circulatory arrest or cardiac arrest or cardiopulmonary arrest. The unexpected cardiac arrest is medically referred to as sudden cardiac arrest (SCA). Poor survival rate of patients with SCA is one of themost ubiquitous health care problems today. Recent studies show that heart-rate-derived features can act as early predictors of SCA. Addition of angiographic and electrophysiological features can increase the robustness of the prediction system. Early warning has the capability of saving many lives. Risk of recurrent terminal cardiac arrest is high for out-of-hospital survivors. Foregoing studies indicate that recurrent cardiac events are time dependent and, while in clinical follow-up, are highly probable, predominantly in early phase. In this paper, we observe the changing risk of and changing influence of various clinical, angiographic and electrophysiological parameters on subsequent cardiac arrest recurrence with time. Various medical and synthetic datasets such as ECG dataset from PhysioNet, Pima Indian Diabetes dataset from UCI Machine Learning Repository and gene expression dataset from GEO are used, which are unique as compared with related works. Various classifiers such as LogitBoost with simple regression function, random forest and multilayer perceptron are used for recurrence risk prediction. Collection of these classifiers together forms the ensemble classifiers. Classifiers are compared based on various measures like accuracy and precision. Based on the classification, risk scores are calculated using logistic regression with backward elimination. The proposed method is used for final risk estimation. The same datasets are used for risk score calculation model development. Experimental results are found to be encouraging.

  13. Determinants of biventricular cardiac function: a mathematical model study on geometry and myofiber orientation.

    Science.gov (United States)

    Pluijmert, Marieke; Delhaas, Tammo; de la Parra, Adrián Flores; Kroon, Wilco; Prinzen, Frits W; Bovendeerd, Peter H M

    2017-04-01

    In patient-specific mathematical models of cardiac electromechanics, usually a patient-specific geometry and a generic myofiber orientation field are used as input, upon which myocardial tissue properties are tuned to clinical data. It remains unclear to what extent deviations in myofiber orientation and geometry between model and patient influence model predictions on cardiac function. Therefore, we evaluated the sensitivity of cardiac function for geometry and myofiber orientation in a biventricular (BiV) finite element model of cardiac mechanics. Starting out from a reference geometry in which myofiber orientation had no transmural component, two new geometries were defined with either a 27 % decrease in LV short- to long-axis ratio, or a 16 % decrease of RV length, but identical LV and RV cavity and wall volumes. These variations in geometry caused differences in both local myofiber and global pump work below 6 %. Variation of fiber orientation was induced through adaptive myofiber reorientation that caused an average change in fiber orientation of [Formula: see text] predominantly through the formation of a component in transmural direction. Reorientation caused a considerable increase in local myofiber work [Formula: see text] and in global pump work [Formula: see text] in all three geometries, while differences between geometries were below 5 %. The findings suggest that implementing a realistic myofiber orientation is at least as important as defining a patient-specific geometry. The model for remodeling of myofiber orientation seems a useful approach to estimate myofiber orientation in the absence of accurate patient-specific information.

  14. Drug-induced proarrhythmia: risk factors and electrophysiological mechanisms.

    Science.gov (United States)

    Frommeyer, Gerrit; Eckardt, Lars

    2016-01-01

    Drug-induced ventricular tachyarrhythmias can be caused by cardiovascular drugs, noncardiovascular drugs, and even nonprescription agents. They can result in arrhythmic emergencies and sudden cardiac death. If a new arrhythmia or aggravation of an existing arrhythmia develops during therapy with a drug at a concentration usually considered not to be toxic, the situation can be defined as proarrhythmia. Various cardiovascular and noncardiovascular drugs can increase the occurrence of polymorphic ventricular tachycardia of the 'torsade de pointes' type. Antiarrhythmic drugs, antimicrobial agents, and antipsychotic and antidepressant drugs are the most important groups. Age, female sex, and structural heart disease are important risk factors for the occurrence of torsade de pointes. Genetic predisposition and individual pharmacodynamic and pharmacokinetic sensitivity also have important roles in the generation of arrhythmias. An increase in spatial or temporal dispersion of repolarization and a triangular action-potential configuration have been identified as crucial predictors of proarrhythmia in experimental models. These studies emphasized that sole consideration of the QT interval is not sufficient to assess the proarrhythmic risk. In this Review, we focus on important triggers of proarrhythmia and the underlying electrophysiological mechanisms that can enhance or prevent the development of torsade de pointes.

  15. Modeling calcium wave based on anomalous subdiffusion of calcium sparks in cardiac myocytes.

    Directory of Open Access Journals (Sweden)

    Xi Chen

    Full Text Available Ca(2+ sparks and Ca(2+ waves play important roles in calcium release and calcium propagation during the excitation-contraction (EC coupling process in cardiac myocytes. Although the classical Fick's law is widely used to model Ca(2+ sparks and Ca(2+ waves in cardiac myocytes, it fails to reasonably explain the full-width at half maximum(FWHM paradox. However, the anomalous subdiffusion model successfully reproduces Ca(2+ sparks of experimental results. In this paper, in the light of anomalous subdiffusion of Ca(2+ sparks, we develop a mathematical model of calcium wave in cardiac myocytes by using stochastic Ca(2+ release of Ca(2+ release units (CRUs. Our model successfully reproduces calcium waves with physiological parameters. The results reveal how Ca(2+ concentration waves propagate from an initial firing of one CRU at a corner or in the middle of considered region, answer how large in magnitude of an anomalous Ca(2+ spark can induce a Ca(2+ wave. With physiological Ca(2+ currents (2pA through CRUs, it is shown that an initial firing of four adjacent CRUs can form a Ca(2+ wave. Furthermore, the phenomenon of calcium waves collision is also investigated.

  16. Image-Based Structural Modeling of the Cardiac Purkinje Network

    Directory of Open Access Journals (Sweden)

    Benjamin R. Liu

    2015-01-01

    Full Text Available The Purkinje network is a specialized conduction system within the heart that ensures the proper activation of the ventricles to produce effective contraction. Its role during ventricular arrhythmias is less clear, but some experimental studies have suggested that the Purkinje network may significantly affect the genesis and maintenance of ventricular arrhythmias. Despite its importance, few structural models of the Purkinje network have been developed, primarily because current physical limitations prevent examination of the intact Purkinje network. In previous modeling efforts Purkinje-like structures have been developed through either automated or hand-drawn procedures, but these networks have been created according to general principles rather than based on real networks. To allow for greater realism in Purkinje structural models, we present a method for creating three-dimensional Purkinje networks based directly on imaging data. Our approach uses Purkinje network structures extracted from photographs of dissected ventricles and projects these flat networks onto realistic endocardial surfaces. Using this method, we create models for the combined ventricle-Purkinje system that can fully activate the ventricles through a stimulus delivered to the Purkinje network and can produce simulated activation sequences that match experimental observations. The combined models have the potential to help elucidate Purkinje network contributions during ventricular arrhythmias.

  17. Diesel Exhaust Inhalation Increases Cardiac Output, Bradyarrhythmias, and Parasympathetic Tone in Aged Heart Failure-Prone Rats

    Science.gov (United States)

    Acute air pollutant inhalation is linked to adverse cardiac events and death, and hospitalizations for heart failure. Diesel exhaust (DE) is a major air pollutant suspected to exacerbate preexisting cardiac conditions, in part, through autonomic and electrophysiologic disturbance...

  18. Finite element model to study two dimensional unsteady state calcium distribution in cardiac myocytes

    Directory of Open Access Journals (Sweden)

    Kunal Pathak

    2016-09-01

    Full Text Available The calcium signaling plays a crucial role in expansion and contraction of cardiac myocytes. This calcium signaling is achieved by calcium diffusion, buffering mechanisms and influx in cardiac myocytes. The various calcium distribution patterns required for achieving calcium signaling in myocytes are still not well understood. In this paper an attempt has been made to develop a model of calcium distribution in myocytes incorporating diffusion of calcium, point source and excess buffer approximation. The model has been developed for a two dimensional unsteady state case. Appropriate boundary conditions and initial condition have been framed. The finite element method has been employed to obtain the solution. The numerical results have been used to study the effect of buffers and source amplitude on calcium distribution in myocytes.

  19. Modeling of cardiac muscle thin films: pre-stretch, passive and active behavior.

    Science.gov (United States)

    Shim, Jongmin; Grosberg, Anna; Nawroth, Janna C; Parker, Kevin Kit; Bertoldi, Katia

    2012-03-15

    Recent progress in tissue engineering has made it possible to build contractile bio-hybrid materials that undergo conformational changes by growing a layer of cardiac muscle on elastic polymeric membranes. Further development of such muscular thin films for building actuators and powering devices requires exploring several design parameters, which include the alignment of the cardiac myocytes and the thickness/Young's modulus of elastomeric film. To more efficiently explore these design parameters, we propose a 3-D phenomenological constitutive model, which accounts for both the passive deformation including pre-stretch and the active behavior of the cardiomyocytes. The proposed 3-D constitutive model is implemented within a finite element framework, and can be used to improve the current design of bio-hybrid thin films and help developing bio-hybrid constructs capable of complex conformational changes. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. Coexisting chaotic and multi-periodic dynamics in a model of cardiac alternans

    Energy Technology Data Exchange (ETDEWEB)

    Skardal, Per Sebastian, E-mail: skardals@gmail.com [Departament d' Enginyeria Informàtica i Matemàtiques, Universitat Rovira i Virgili, 43007 Tarragona (Spain); Restrepo, Juan G., E-mail: juanga@colorado.edu [Department of Applied Mathematics, University of Colorado, Boulder, Colorado 80309 (United States)

    2014-12-15

    The spatiotemporal dynamics of cardiac tissue is an active area of research for biologists, physicists, and mathematicians. Of particular interest is the study of period-doubling bifurcations and chaos due to their link with cardiac arrhythmogenesis. In this paper, we study the spatiotemporal dynamics of a recently developed model for calcium-driven alternans in a one dimensional cable of tissue. In particular, we observe in the cable coexistence of regions with chaotic and multi-periodic dynamics over wide ranges of parameters. We study these dynamics using global and local Lyapunov exponents and spatial trajectory correlations. Interestingly, near nodes—or phase reversals—low-periodic dynamics prevail, while away from the nodes, the dynamics tend to be higher-periodic and eventually chaotic. Finally, we show that similar coexisting multi-periodic and chaotic dynamics can also be observed in a detailed ionic model.

  1. An eikonal approach for the initiation of reentrant cardiac propagation in reaction-diffusion models.

    Science.gov (United States)

    Jacquemet, Vincent

    2010-09-01

    Microscale electrical propagation in the heart can be modeled by a reaction-diffusion system, describing cell and tissue electrophysiology. Macroscale features of wavefront propagation can be reproduced by an eikonal model, a reduced formulation involving only wavefront shape. In this paper, these two approaches are combined to incorporate global information about reentrant pathways into a reaction-diffusion model. The eikonal-diffusion formulation is generalized to handle reentrant activation patterns and wavefront collisions. Boundary conditions are used to specify pathways of reentry. Finite-element-based numerical methods are presented to solve this nonlinear equation on a coarse triangular mesh. The macroscale eikonal model serves to construct an initial condition for the microscale reaction-diffusion model. Electrical propagation simulated from this initial condition is then compared to the isochrones predicted by the eikonal model. Results in 2-D and thin 3-D test-case geometries demonstrate the ability of this technique to initiate anatomical and functional reentries along prescribed pathways, thus facilitating the development of dedicated models aimed at better understanding clinical case reports.

  2. Adjustment of Dysregulated Ceramide Metabolism in a Murine Model of Sepsis-Induced Cardiac Dysfunction.

    Science.gov (United States)

    Chung, Ha-Yeun; Kollmey, Anna S; Schrepper, Andrea; Kohl, Matthias; Bläss, Markus F; Stehr, Sebastian N; Lupp, Amelie; Gräler, Markus H; Claus, Ralf A

    2017-04-15

    Cardiac dysfunction, in particular of the left ventricle, is a common and early event in sepsis, and is strongly associated with an increase in patients' mortality. Acid sphingomyelinase (SMPD1)-the principal regulator for rapid and transient generation of the lipid mediator ceramide-is involved in both the regulation of host response in sepsis as well as in the pathogenesis of chronic heart failure. This study determined the degree and the potential role to which SMPD1 and its modulation affect sepsis-induced cardiomyopathy using both genetically deficient and pharmacologically-treated animals in a polymicrobial sepsis model. As surrogate parameters of sepsis-induced cardiomyopathy, cardiac function, markers of oxidative stress as well as troponin I levels were found to be improved in desipramine-treated animals, desipramine being an inhibitor of ceramide formation. Additionally, ceramide formation in cardiac tissue was dysregulated in SMPD1(+/+) as well as SMPD1(-/-) animals, whereas desipramine pretreatment resulted in stable, but increased ceramide content during host response. This was a result of elevated de novo synthesis. Strikingly, desipramine treatment led to significantly improved levels of surrogate markers. Furthermore, similar results in desipramine-pretreated SMPD1(-/-) littermates suggest an SMPD1-independent pathway. Finally, a pattern of differentially expressed transcripts important for regulation of apoptosis as well as antioxidative and cytokine response supports the concept that desipramine modulates ceramide formation, resulting in beneficial myocardial effects. We describe a novel, protective role of desipramine during sepsis-induced cardiac dysfunction that controls ceramide content. In addition, it may be possible to modulate cardiac function during host response by pre-conditioning with the Food and Drug Administration (FDA)-approved drug desipramine.

  3. In vivo MRI characterization of progressive cardiac dysfunction in the mdx mouse model of muscular dystrophy.

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    Daniel J Stuckey

    Full Text Available AIMS: The mdx mouse has proven to be useful in understanding the cardiomyopathy that frequently occurs in muscular dystrophy patients. Here we employed a comprehensive array of clinically relevant in vivo MRI techniques to identify early markers of cardiac dysfunction and follow disease progression in the hearts of mdx mice. METHODS AND RESULTS: Serial measurements of cardiac morphology and function were made in the same group of mdx mice and controls (housed in a non-SPF facility using MRI at 1, 3, 6, 9 and 12 months after birth. Left ventricular (LV and right ventricular (RV systolic and diastolic function, response to dobutamine stress and myocardial fibrosis were assessed. RV dysfunction preceded LV dysfunction, with RV end systolic volumes increased and RV ejection fractions reduced at 3 months of age. LV ejection fractions were reduced at 12 months, compared with controls. An abnormal response to dobutamine stress was identified in the RV of mdx mice as early as 1 month. Late-gadolinium-enhanced MRI identified increased levels of myocardial fibrosis in 6, 9 and 12-month-old mdx mice, the extent of fibrosis correlating with the degree of cardiac remodeling and hypertrophy. CONCLUSIONS: MRI could identify cardiac abnormalities in the RV of mdx mice as young as 1 month, and detected myocardial fibrosis at 6 months. We believe these to be the earliest MRI measurements of cardiac function reported for any mice, and the first use of late-gadolinium-enhancement in a mouse model of congenital cardiomyopathy. These techniques offer a sensitive and clinically relevant in vivo method for assessment of cardiomyopathy caused by muscular dystrophy and other diseases.

  4. Pseudoxanthoma elasticum: cardiac findings in patients and Abcc6-deficient mouse model.

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    Fabrice Prunier

    Full Text Available BACKGROUND: Pseudoxanthoma elasticum (PXE, caused by mutations in the ABCC6 gene, is a rare multiorgan disease characterized by the mineralization and fragmentation of elastic fibers in connective tissue. Cardiac complications reportedly associated with PXE are mainly based on case reports. METHODS: A cohort of 67 PXE patients was prospectively assessed. Patients underwent physical examination, electrocardiogram, transthoracic echocardiography, cardiac magnetic resonance imaging (CMR, treadmill testing, and perfusion myocardial scintigraphy (SPECT. Additionally, the hearts of a PXE mouse models (Abcc6(-/- and wild-type controls (WT were analyzed. RESULTS: Three patients had a history of proven coronary artery disease. In total, 40 patients underwent exercise treadmill tests, and 28 SPECT. The treadmill tests were all negative. SPECT showed mild perfusion abnormalities in two patients. Mean left ventricular (LV dimension and function values were within the normal range. LV hypertrophy was found in 7 (10.4% patients, though the hypertrophy etiology was unknown for 3 of those patients. Echocardiography revealed frequent but insignificant mitral and tricuspid valvulopathies. Mitral valve prolapse was present in 3 patients (4.5%. Two patients exhibited significant aortic stenosis (3.0%. While none of the functional and histological parameters diverged significantly between the Abcc6(-/- and WT mice groups at age of 6 and 12 months, the 24-month-old Abcc6(-/- mice developed cardiac hypertrophy without contractile dysfunction. CONCLUSIONS: Despite sporadic cases, PXE does not appear to be associated with frequent cardiac complications. However, the development of cardiac hypertrophy in the 24-month-old Abcc6(-/- mice suggests that old PXE patients might be prone to developing late cardiopathy.

  5. GPU accelerated solver for nonlinear reaction-diffusion systems. Application to the electrophysiology problem

    Science.gov (United States)

    Mena, Andres; Ferrero, Jose M.; Rodriguez Matas, Jose F.

    2015-11-01

    Solving the electric activity of the heart possess a big challenge, not only because of the structural complexities inherent to the heart tissue, but also because of the complex electric behaviour of the cardiac cells. The multi-scale nature of the electrophysiology problem makes difficult its numerical solution, requiring temporal and spatial resolutions of 0.1 ms and 0.2 mm respectively for accurate simulations, leading to models with millions degrees of freedom that need to be solved for thousand time steps. Solution of this problem requires the use of algorithms with higher level of parallelism in multi-core platforms. In this regard the newer programmable graphic processing units (GPU) has become a valid alternative due to their tremendous computational horsepower. This paper presents results obtained with a novel electrophysiology simulation software entirely developed in Compute Unified Device Architecture (CUDA). The software implements fully explicit and semi-implicit solvers for the monodomain model, using operator splitting. Performance is compared with classical multi-core MPI based solvers operating on dedicated high-performance computer clusters. Results obtained with the GPU based solver show enormous potential for this technology with accelerations over 50 × for three-dimensional problems.

  6. Ventricular fibrillation-induced cardiac arrest in the rat as a model of global cerebral ischemia

    OpenAIRE

    Dave, Kunjan R.; DELLA-MORTE, DAVID; Saul, Isabel; Prado, Ricardo; Perez-Pinzon, Miguel A

    2013-01-01

    Cardiopulmonary arrest remains one of the leading causes of death and disability in Western countries. Although ventricular fibrillation (VF) models in rodents mimic the “square wave” type of insult (rapid loss of pulse and pressure) commonly observed in adult humans at the onset of cardiac arrest (CA), they are not popular because of the complicated animal procedure, poor animal survival and thermal injury. Here we present a modified, simple, reliable, ventricular fibrillation-induced rat mo...

  7. Standardized echocardiographic assessment of cardiac function in normal adult zebrafish and heart disease models

    Science.gov (United States)

    Wang, Louis W.; Huttner, Inken G.; Santiago, Celine F.; Kesteven, Scott H.; Yu, Ze-Yan; Feneley, Michael P.

    2017-01-01

    ABSTRACT The zebrafish (Danio rerio) is an increasingly popular model organism in cardiovascular research. Major insights into cardiac developmental processes have been gained by studies of embryonic zebrafish. However, the utility of zebrafish for modeling adult-onset heart disease has been limited by a lack of robust methods for in vivo evaluation of cardiac function. We established a physiological protocol for underwater zebrafish echocardiography using high frequency ultrasound, and evaluated its reliability in detecting altered cardiac function in two disease models. Serial assessment of cardiac function was performed in wild-type zebrafish aged 3 to 12 months and the effects of anesthetic agents, age, sex and background strain were evaluated. There was a varying extent of bradycardia and ventricular contractile impairment with different anesthetic drugs and doses, with tricaine 0.75 mmol l−1 having a relatively more favorable profile. When compared with males, female fish were larger and had more measurement variability. Although age-related increments in ventricular chamber size were greater in females than males, there were no sex differences when data were normalized to body size. Systolic ventricular function was similar in both sexes at all time points, but differences in diastolic function were evident from 6 months onwards. Wild-type fish of both sexes showed a reliance on atrial contraction for ventricular diastolic filling. Echocardiographic evaluation of adult zebrafish with diphtheria toxin-induced myocarditis or anemia-induced volume overload accurately identified ventricular dilation and altered contraction, with suites of B-mode, ventricular strain, pulsed-wave Doppler and tissue Doppler indices showing concordant changes indicative of myocardial hypocontractility or hypercontractility, respectively. Repeatability, intra-observer and inter-observer correlations for echocardiographic measurements were high. We demonstrate that high

  8. Functional 3-D cardiac co-culture model using bioactive chitosan nanofiber scaffolds.

    Science.gov (United States)

    Hussain, Ali; Collins, George; Yip, Derek; Cho, Cheul H

    2013-02-01

    The in vitro generation of a three-dimensional (3-D) myocardial tissue-like construct employing cells, biomaterials, and biomolecules is a promising strategy in cardiac tissue regeneration, drug testing, and tissue engineering applications. Despite significant progress in this field, current cardiac tissue models are not yet able to stably maintain functional characteristics of cardiomyocytes for long-term culture and therapeutic purposes. The objective of this study was to fabricate bioactive 3-D chitosan nanofiber scaffolds using an electrospinning technique and exploring its potential for long-term cardiac function in the 3-D co-culture model. Chitosan is a natural polysaccharide biomaterial that is biocompatible, biodegradable, non-toxic, and cost effective. Electrospun chitosan was utilized to provide structural scaffolding characterized by scale and architectural resemblance to the extracellular matrix (ECM) in vivo. The chitosan fibers were coated with fibronectin via adsorption in order to enhance cellular adhesion to the fibers and migration into the interfibrous milieu. Ventricular cardiomyocytes were harvested from neonatal rats and studied in various culture conditions (i.e., mono- and co-cultures) for their viability and function. Cellular morphology and functionality were examined using immunofluorescent staining for alpha-sarcomeric actin (SM-actin) and gap junction protein, Connexin-43 (Cx43). Scanning electron microscopy (SEM) and light microscopy were used to investigate cellular morphology, spatial organization, and contractions. Calcium indicator was used to monitor calcium ion flux of beating cardiomyocytes. The results demonstrate that the chitosan nanofibers retained their cylindrical morphology in long-term cell cultures and exhibited good cellular attachment and spreading in the presence of adhesion molecule, fibronectin. Cardiomyocyte mono-cultures resulted in loss of cardiomyocyte polarity and islands of non-coherent contractions. However

  9. Arrhythmia and cardiac defects are a feature of spinal muscular atrophy model mice.

    Science.gov (United States)

    Heier, Christopher R; Satta, Rosalba; Lutz, Cathleen; DiDonato, Christine J

    2010-10-15

    Proximal spinal muscular atrophy (SMA) is the leading genetic cause of infant mortality. Traditionally, SMA has been described as a motor neuron disease; however, there is a growing body of evidence that arrhythmia and/or cardiomyopathy may present in SMA patients at an increased frequency. Here, we ask whether SMA model mice possess such phenotypes. We find SMA mice suffer from severe bradyarrhythmia characterized by progressive heart block and impaired ventricular depolarization. Echocardiography further confirms functional cardiac deficits in SMA mice. Additional investigations show evidence of both sympathetic innervation defects and dilated cardiomyopathy at late stages of disease. Based upon these data, we propose a model in which decreased sympathetic innervation causes autonomic imbalance. Such imbalance would be characterized by a relative increase in the level of vagal tone controlling heart rate, which is consistent with bradyarrhythmia and progressive heart block. Finally, treatment with the histone deacetylase inhibitor trichostatin A, a drug known to benefit phenotypes of SMA model mice, produces prolonged maturation of the SMA heartbeat and an increase in cardiac size. Treated mice maintain measures of motor function throughout extended survival though they ultimately reach death endpoints in association with a progression of bradyarrhythmia. These data represent the novel identification of cardiac arrhythmia as an early and progressive feature of murine SMA while providing several new, quantitative indices of mouse health. Together with clinical cases that report similar symptoms, this reveals a new area of investigation that will be important to address as we move SMA therapeutics towards clinical success.

  10. A boolean model of the cardiac gene regulatory network determining first and second heart field identity.

    Directory of Open Access Journals (Sweden)

    Franziska Herrmann

    Full Text Available Two types of distinct cardiac progenitor cell populations can be identified during early heart development: the first heart field (FHF and second heart field (SHF lineage that later form the mature heart. They can be characterized by differential expression of transcription and signaling factors. These regulatory factors influence each other forming a gene regulatory network. Here, we present a core gene regulatory network for early cardiac development based on published temporal and spatial expression data of genes and their interactions. This gene regulatory network was implemented in a Boolean computational model. Simulations reveal stable states within the network model, which correspond to the regulatory states of the FHF and the SHF lineages. Furthermore, we are able to reproduce the expected temporal expression patterns of early cardiac factors mimicking developmental progression. Additionally, simulations of knock-down experiments within our model resemble published phenotypes of mutant mice. Consequently, this gene regulatory network retraces the early steps and requirements of cardiogenic mesoderm determination in a way appropriate to enhance the understanding of heart development.

  11. A Boolean Model of the Cardiac Gene Regulatory Network Determining First and Second Heart Field Identity

    Science.gov (United States)

    Zhou, Dao; Kestler, Hans A.; Kühl, Michael

    2012-01-01

    Two types of distinct cardiac progenitor cell populations can be identified during early heart development: the first heart field (FHF) and second heart field (SHF) lineage that later form the mature heart. They can be characterized by differential expression of transcription and signaling factors. These regulatory factors influence each other forming a gene regulatory network. Here, we present a core gene regulatory network for early cardiac development based on published temporal and spatial expression data of genes and their interactions. This gene regulatory network was implemented in a Boolean computational model. Simulations reveal stable states within the network model, which correspond to the regulatory states of the FHF and the SHF lineages. Furthermore, we are able to reproduce the expected temporal expression patterns of early cardiac factors mimicking developmental progression. Additionally, simulations of knock-down experiments within our model resemble published phenotypes of mutant mice. Consequently, this gene regulatory network retraces the early steps and requirements of cardiogenic mesoderm determination in a way appropriate to enhance the understanding of heart development. PMID:23056457

  12. Large-deflection statics analysis of active cardiac catheters through co-rotational modelling.

    Science.gov (United States)

    Peng Qi; Chen Qiu; Mehndiratta, Aadarsh; I-Ming Chen; Haoyong Yu

    2016-08-01

    This paper presents a co-rotational concept for large-deflection formulation of cardiac catheters. Using this approach, the catheter is first discretized with a number of equal length beam elements and nodes, and the rigid body motions of an individual beam element are separated from its deformations. Therefore, it is adequate for modelling arbitrarily large deflections of a catheter with linear elastic analysis at the local element level. A novel design of active cardiac catheter of 9 Fr in diameter at the beginning of the paper is proposed, which is based on the contra-rotating double helix patterns and is improved from the previous prototypes. The modelling section is followed by MATLAB simulations of various deflections when the catheter is exerted different types of loads. This proves the feasibility of the presented modelling approach. To the best knowledge of the authors, it is the first to utilize this methodology for large-deflection static analysis of the catheter, which will enable more accurate control of robot-assisted cardiac catheterization procedures. Future work would include further experimental validations.

  13. Four-dimensional modeling of the heart for image guidance of minimally invasive cardiac surgeries

    Science.gov (United States)

    Wierzbicki, Marcin; Drangova, Maria; Guiraudon, Gerard; Peters, Terry

    2004-05-01

    Minimally invasive surgery of the beating heart can be associated with two major limitations: selecting port locations for optimal target coverage from x-rays and angiograms, and navigating instruments in a dynamic and confined 3D environment using only an endoscope. To supplement the current surgery planning and guidance strategies, we continue developing VCSP - a virtual reality, patient-specific, thoracic cavity model derived from 3D pre-procedural images. In this work, we apply elastic image registration to 4D cardiac images to model the dynamic heart. Our method is validated on two image modalities, and for different parts of the cardiac anatomy. In a helical CT dataset of an excised heart phantom, we found that the artificial motion of the epicardial surface can be extracted to within 0.93 +/- 0.33 mm. For an MR dataset of a human volunteer, the error for different heart structures such as the myocardium, right and left atria, right ventricle, aorta, vena cava, and pulmonary artery, ranged from 1.08 +/- 0.18 mm to 1.14 +/- 0.22 mm. These results indicate that our method of modeling the motion of the heart is not only easily adaptable but also sufficiently accurate to meet the requirements for reliable cardiac surgery training, planning, and guidance.

  14. Mechano-chemical Interactions in Cardiac Sarcomere Contraction: A Computational Modeling Study

    Science.gov (United States)

    Lumens, Joost; Arts, Theo; Delhaas, Tammo

    2016-01-01

    We developed a model of cardiac sarcomere contraction to study the calcium-tension relationship in cardiac muscle. Calcium mediates cardiac contraction through its interactions with troponin (Tn) and subsequently tropomyosin molecules. Experimental studies have shown that a slight increase in intracellular calcium concentration leads to a rapid increase in sarcomeric tension. Though it is widely accepted that the rapid increase is not possible without the concept of cooperativity, the mechanism is debated. We use the hypothesis that there exists a base level of cooperativity intrinsic to the thin filament that is boosted by mechanical tension, i.e. a high level of mechanical tension in the thin filament impedes the unbinding of calcium from Tn. To test these hypotheses, we developed a computational model in which a set of three parameters and inputs of calcium concentration and sarcomere length result in output tension. Tension as simulated appeared in good agreement with experimentally measured tension. Our results support the hypothesis that high tension in the thin filament impedes Tn deactivation by increasing the energy required to detach calcium from the Tn. Given this hypothesis, the model predicted that the areas with highest tension, i.e. closest to the Z-disk end of the single overlap region, show the largest concentration of active Tn’s. PMID:27716775

  15. Analyses of the redistribution of work following cardiac resynchronisation therapy in a patient specific model.

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    Steven Alexander Niederer

    Full Text Available Regulation of regional work is essential for efficient cardiac function. In patients with heart failure and electrical dysfunction such as left branch bundle block regional work is often depressed in the septum. Following cardiac resynchronisation therapy (CRT this heterogeneous distribution of work can be rebalanced by altering the pattern of electrical activation. To investigate the changes in regional work in these patients and the mechanisms underpinning the improved function following CRT we have developed a personalised computational model. Simulations of electromechanical cardiac function in the model estimate the regional stress, strain and work pre- and post-CRT. These simulations predict that the increase in observed work performed by the septum following CRT is not due to an increase in the volume of myocardial tissue recruited during contraction but rather that the volume of recruited myocardium remains the same and the average peak work rate per unit volume increases. These increases in the peak average rate of work is is attributed to slower and more effective contraction in the septum, as opposed to a change in active tension. Model results predict that this improved septal work rate following CRT is a result of resistance to septal contraction provided by the LV free wall. This resistance results in septal shortening over a longer period which, in turn, allows the septum to contract while generating higher levels of active tension to produce a higher work rate.

  16. Stochastic heart-rate model can reveal pathologic cardiac dynamics

    Science.gov (United States)

    Kuusela, Tom

    2004-03-01

    A simple one-dimensional Langevin-type stochastic difference equation can simulate the heart-rate fluctuations in a time scale from minutes to hours. The model consists of a deterministic nonlinear part and a stochastic part typical of Gaussian noise, and both parts can be directly determined from measured heart-rate data. Data from healthy subjects typically exhibit the deterministic part with two or more stable fixed points. Studies of 15 congestive heart-failure subjects reveal that the deterministic part of pathologic heart dynamics has no clear stable fixed points. Direct simulations of the stochastic model for normal and pathologic cases can produce statistical parameters similar to those of real subjects. Results directly indicate that pathologic situations simplify the heart-rate control system.

  17. Electrophysiology and Biopotential Issues on Human Electrocardiogram-A Review

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    Mahmoud A.S. Ali

    2011-01-01

    Full Text Available Problem statement: The heart is the first organ and most importantly to form in the body, where is found the most powerful generator of electromagnetic energy in the human body. Electrophysiology is the best method used to diagnose human heart problem. Knowledge of the electrical potentials in human heart is a quantum leap in the science of the human heart. Recently, there has been a growing interest in studying the human ECG. However, is unfortunately a very complicated issue which requires a relatively good understanding of everything that has been said about the heart. Focus on the review of physical, electromagnetic basis of human heart's biopotentials and understanding the basic equations of cardiac electrophysiology that represents the basis to all clinicians whether in postnatal (pediatric or adult or prenatal (foetal Medicine. Approach: Mathematical method used for derivation of the essential equations of human heart electrical potentials, this equation will develop the principle sciences of human heart, the equation also outlier finding of the electromagnetic base of human electrophysiology. Results: Heart is important electrical generator in human body. The voltage and current which was generated in human heart represent the basis of heart biosciences. The electromagnetic energy of the heart not only envelops every cell of the human body, but also extends out in all directions in the space around human body. Conclusion: The proposed technique for electrophysiology and potentials on human ECG was useful and the results may contribute to the references for later studies.

  18. Efficient parameterization of cardiac action potential models using a genetic algorithm

    Science.gov (United States)

    Cairns, Darby I.; Fenton, Flavio H.; Cherry, E. M.

    2017-09-01

    Finding appropriate values for parameters in mathematical models of cardiac cells is a challenging task. Here, we show that it is possible to obtain good parameterizations in as little as 30-40 s when as many as 27 parameters are fit simultaneously using a genetic algorithm and two flexible phenomenological models of cardiac action potentials. We demonstrate how our implementation works by considering cases of "model recovery" in which we attempt to find parameter values that match model-derived action potential data from several cycle lengths. We assess performance by evaluating the parameter values obtained, action potentials at fit and non-fit cycle lengths, and bifurcation plots for fidelity to the truth as well as consistency across different runs of the algorithm. We also fit the models to action potentials recorded experimentally using microelectrodes and analyze performance. We find that our implementation can efficiently obtain model parameterizations that are in good agreement with the dynamics exhibited by the underlying systems that are included in the fitting process. However, the parameter values obtained in good parameterizations can exhibit a significant amount of variability, raising issues of parameter identifiability and sensitivity. Along similar lines, we also find that the two models differ in terms of the ease of obtaining parameterizations that reproduce model dynamics accurately, most likely reflecting different levels of parameter identifiability for the two models.

  19. Bifurcations, chaos, and sensitivity to parameter variations in the Sato cardiac cell model

    Science.gov (United States)

    Otte, Stefan; Berg, Sebastian; Luther, Stefan; Parlitz, Ulrich

    2016-08-01

    The dynamics of a detailed ionic cardiac cell model proposed by Sato et al. (2009) is investigated in terms of periodic and chaotic action potentials, bifurcation scenarios, and coexistence of attractors. Starting from the model's standard parameter values bifurcation diagrams are computed to evaluate the model's robustness with respect to (small) parameter changes. While for some parameters the dynamics turns out to be practically independent from their values, even minor changes of other parameters have a very strong impact and cause qualitative changes due to bifurcations or transitions to coexisting attractors. Implications of this lack of robustness are discussed.

  20. Funny current and cardiac rhythm: insights from HCN knockout mouse models

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    Mirko eBaruscotti

    2012-07-01

    Full Text Available In the adult animal the sinoatrial node (SAN rhythmically generates a depolarizing wave that propagates to the rest of the heart. However, the SAN is more than a simple clock; it is a clock that adjusts its pace according to the metabolic requirements of the organism. The Hyperpolarization-activated Cyclic Nucleotide-gated channels (HCN1-4 are the structural component of the funny (If channels; in the SAN the If current is the main driving electrical force of the diastolic depolarization and the HCN4 is the most abundant isoform. The generation of HCN KO mouse models has advanced the understanding of the role of these channels in cardiac excitability. The HCN4 KO models that were first developed allowed either global or cardiac-specific constitutive ablation of HCN4 channels, and resulted in embryonic lethality. A further progress was made with the development of three separate inducible HCN4 KO models; in one model KO was induced globally in the entire organism, in a second, ablation occurred only in HCN4-expressing cells, and finally in a third model KO was confined to cardiac cells. Unexpectedly, the three models yielded different results; similarities and differences among these models will be presented and discussed. The functional effects of HCN2 and HCN3 knockout models and transgenic HCN4 mouse models will also be discussed.In conclusion, HCN KO/transgenic models have allowed to evaluate the functional role of the If currents in intact animals as well as in single SAN cells isolated from the same animals. This opportunity is therefore unique since it allows to 1 verify the contribution of specific HCN isoforms to cardiac activity in intact animals, and 2 to compare these results to those obtained in single cell experiments. These combined studies were not possible prior to the development of KO models. Finally, these models represent critical tools to improve our understanding of the molecular basis of some inheritable arrhythmic human

  1. Optimizing the phenotyping of rodent ASD models: enrichment analysis of mouse and human neurobiological phenotypes associated with high-risk autism genes identifies morphological, electrophysiological, neurological, and behavioral features

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    Buxbaum Joseph D

    2012-02-01

    Full Text Available Abstract Background There is interest in defining mouse neurobiological phenotypes useful for studying autism spectrum disorders (ASD in both forward and reverse genetic approaches. A recurrent focus has been on high-order behavioral analyses, including learning and memory paradigms and social paradigms. However, well-studied mouse models, including for example Fmr1 knockout mice, do not show dramatic deficits in such high-order phenotypes, raising a question as to what constitutes useful phenotypes in ASD models. Methods To address this, we made use of a list of 112 disease genes etiologically involved in ASD to survey, on a large scale and with unbiased methods as well as expert review, phenotypes associated with a targeted disruption of these genes in mice, using the Mammalian Phenotype Ontology database. In addition, we compared the results with similar analyses for human phenotypes. Findings We observed four classes of neurobiological phenotypes associated with disruption of a large proportion of ASD genes, including: (1 Changes in brain and neuronal morphology; (2 electrophysiological changes; (3 neurological changes; and (4 higher-order behavioral changes. Alterations in brain and neuronal morphology represent quantitative measures that can be more widely adopted in models of ASD to understand cellular and network changes. Interestingly, the electrophysiological changes differed across different genes, indicating that excitation/inhibition imbalance hypotheses for ASD would either have to be so non-specific as to be not falsifiable, or, if specific, would not be supported by the data. Finally, it was significant that in analyses of both mouse and human databases, many of the behavioral alterations were neurological changes, encompassing sensory alterations, motor abnormalities, and seizures, as opposed to higher-order behavioral changes in learning and memory and social behavior paradigms. Conclusions The results indicated that mutations

  2. Hydroxocobalamin and epinephrine both improve survival in a swine model of cyanide-induced cardiac arrest.

    Science.gov (United States)

    Bebarta, Vikhyat S; Pitotti, Rebecca L; Dixon, Patricia S; Valtier, Sandra; Esquivel, Luis; Bush, Anneke; Little, Charles M

    2012-10-01

    To determine whether hydroxocobalamin will improve survival compared with epinephrine and saline solution controls in a model of cyanide-induced cardiac arrest. Forty-five swine (38 to 42 kg) were tracheally intubated, anesthetized, and central venous and arterial continuous cardiovascular monitoring catheters were inserted. Potassium cyanide was infused until cardiac arrest developed, defined as mean arterial pressure less than 30 mm Hg. Animals were treated with standardized mechanical chest compressions and were randomly assigned to receive one of 3 intravenous bolus therapies: hydroxocobalamin, epinephrine, or saline solution (control). All animals were monitored for 60 minutes after cardiac arrest. Additional epinephrine infusions were used in all arms of the study after return of spontaneous circulation for systolic blood pressure less than 90 mm Hg. A sample size of 15 animals per group was determined according to a power of 80%, a survival difference of 0.5, and an α of 0.05. Repeated-measure ANOVA was used to determine statistically significant changes between groups over time. Baseline weight, time to arrest, and cyanide dose at cardiac arrest were similar in the 3 groups. Coronary perfusion pressures with chest compressions were greater than 15 mm Hg in both treatment groups indicating sufficient compression depth. Zero of 15 (95% confidence interval [CI] 0% to 25%) animals in the control group, 11 of 15 (73%; 95% CI 48% to 90%) in the hydroxocobalamin group, and 11 of 15 (73%; 95% CI 48% to 90%) in the epinephrine group survived to the conclusion of the study (Pcyanide levels in the hydroxocobalamin group were also lower than that of the epinephrine group from cardiac arrest through the conclusion of the study. Intravenous hydroxocobalamin and epinephrine both independently improved survival compared with saline solution control in our swine model of cyanide-induced cardiac arrest. Hydroxocobalamin improved mean arterial pressure and pH, decreased

  3. Nonlinear dynamics of the heartbeat II. Subharmonic bifurcations of the cardiac interbeat interval in sinus node disease

    Science.gov (United States)

    Goldberger, Ary L.; Bhargava, Valmik; West, Bruce J.; Mandell, Arnold J.

    1985-10-01

    Changing the coupling of electronic relaxation oscillators may be associated with the emergence of complex periodic behavior. The electrocardiographic record of a patient with the “sick sinus syndrome” demonstrated periodic behavior including subharmonic bifurcations in an attractor of his interbeat interval. Such nonlinear dynamics which may emerge from alterations in the coupling of oscillating pacemakers are not predicted by traditional models in cardiac electrophysiology. An understanding of the nonlinear behavior of physical and mathematical systems may generalize to pathophysiological processes.

  4. A new three-variable mathematical model of action potential propagation in cardiac tissue.

    Science.gov (United States)

    Fenton, Flavio; Karma, Alain

    1996-03-01

    Modeling the electrical activity of the heart, and the complex signaling patterns which underly dangerous arrhythmias such as tachycardia and fibrillation, requires a quantitative model of action potential (AP) propagation. At present, there exist detailed ionic models of the Hodgkin-Huxley form that accurately reproduce dynamical features of the AP at a single cell level (e.g. Luo-Rudy, 1994). However, such models are not computationally tractable to study propagation in two and three-dimensional tissues of many resistively coupled cells. At the other extreme, there exists generic models of excitable media, such as the well-known FitzHugh-Nagumo model, which are only qualitative and do not reproduce essential dynamical features of cardiac AP. A new three-variable model is introduced which bridges the gap between these two types of models. It reproduces quantitatively important `mesoscopic' dynamical properties which are specific to cardiac AP, namely restitution and dispersion. At the same time, it remains computationally tractable and makes it possible to study the effect of these properties on the initiation, dynamics, and stability of complex reentrant excitations in two and three dimensions. Preliminary numerical results of the effect of restitution and dispersion on two-dimensional reentry (i.e. spiral waves) are presented.

  5. Cardiac Meets Skeletal: What’s New in Microfluidic Models for Muscle Tissue Engineering

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    Roberta Visone

    2016-08-01

    Full Text Available In the last few years microfluidics and microfabrication technique principles have been extensively exploited for biomedical applications. In this framework, organs-on-a-chip represent promising tools to reproduce key features of functional tissue units within microscale culture chambers. These systems offer the possibility to investigate the effects of biochemical, mechanical, and electrical stimulations, which are usually applied to enhance the functionality of the engineered tissues. Since the functionality of muscle tissues relies on the 3D organization and on the perfect coupling between electrochemical stimulation and mechanical contraction, great efforts have been devoted to generate biomimetic skeletal and cardiac systems to allow high-throughput pathophysiological studies and drug screening. This review critically analyzes microfluidic platforms that were designed for skeletal and cardiac muscle tissue engineering. Our aim is to highlight which specific features of the engineered systems promoted a typical reorganization of the engineered construct and to discuss how promising design solutions exploited for skeletal muscle models could be applied to improve cardiac tissue models and vice versa.

  6. Nos3-/- iPSCs model concordant signatures of in utero cardiac pathogenesis.

    Science.gov (United States)

    Campbell, Katherine A; Li, Xing; Biendarra, Sherri M; Terzic, Andre; Nelson, Timothy J

    2015-10-01

    Through genome-wide transcriptional comparisons, this study interrogates the capacity of in vitro differentiation of induced pluripotent stem cells (iPSCs) to accurately model pathogenic signatures of developmental cardiac defects. Herein, we studied the molecular etiology of cardiac defects in Nos3(-/-) mice via transcriptional analysis of stage-matched embryonic tissues and iPSC-derived cells. In vitro comparisons of differentiated cells were calibrated to in utero benchmarks of health and disease. Integrated systems biology analysis of WT and Nos3(-/-) transcriptional profiles revealed 50% concordant expression patterns between in utero embryonic tissues and ex vivo iPSC-derived cells. In particular, up-regulation of glucose metabolism (p-value=3.95×10(-12)) and down-regulation of fatty acid metabolism (p-value=6.71×10(-12)) highlight a bioenergetic signature of early Nos3 deficiency during cardiogenesis that can be recapitulated in iPSC-derived differentiated cells. The in vitro concordance of early Nos3(-/-) disease signatures supports the utility of iPSCs as a cellular model of developmental heart defects. Moreover, this study supports the use of iPSCs as a platform to pinpoint initial stages of congenital cardiac pathogenesis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Temperature, geometry, and bifurcations in the numerical modeling of the cardiac mechano-electric feedback

    Science.gov (United States)

    Collet, A.; Bragard, J.; Dauby, P. C.

    2017-09-01

    This article characterizes the cardiac autonomous electrical activity induced by the mechanical deformations in the cardiac tissue through the mechano-electric feedback. A simplified and qualitative model is used to describe the system and we also account for temperature effects. The analysis emphasizes a very rich dynamics for the system, with periodic solutions, alternans, chaotic behaviors, etc. The possibility of self-sustained oscillations is analyzed in detail, particularly in terms of the values of important parameters such as the dimension of the system and the importance of the stretch-activated currents. It is also shown that high temperatures notably increase the parameter ranges for which self-sustained oscillations are observed and that several attractors can appear, depending on the location of the initial excitation of the system. Finally, the instability mechanisms by which the periodic solutions are destabilized have been studied by a Floquet analysis, which has revealed period-doubling phenomena and transient intermittencies.

  8. Coexisting chaotic and multi-periodic dynamics in a model of cardiac alternans

    CERN Document Server

    Skardal, Per Sebastian

    2014-01-01

    The spatiotemporal dynamics of cardiac tissue is an active area of research for biologists, physicists, and mathematicians. Of particular interest is the study of period-doubling bifurcations and chaos due to their link with cardiac arrhythmogenesis. In this paper we study the spatiotemporal dynamics of a recently developed model for calcium-driven alternans in a one dimensional cable of tissue. In particular, we observe in the cable coexistence in of regions with chaotic and multi-periodic dynamics over wide ranges of parameters. We study these dynamics using global and local Lyapunov exponents and spatial trajectory correlations. Interestingly, near nodes -- or phase reversals -- low-periodic dynamics prevail, while away from the nodes the dynamics tend to be higher-periodic and eventually chaotic.

  9. Evaluation of cardiac output from a tidally ventilated homogeneous lung model.

    Science.gov (United States)

    Benallal, Habib; Beck, Kenneth C; Johnson, Bruce D; Busso, Thierry

    2005-10-01

    We used the direct Fick measurements to validate a method for estimating cardiac output by iteratively fitting VCO(2) at the mouth to lung model values. This model was run using a series of 50, 30 and 10 breaths to test sensitivity to number of breaths used for fitting. The lung was treated as a catenary two-compartment lung model consisting of a dead space compartment connected with a single alveolar space compartment, perfused with constant pulmonary blood flow. The implemented mathematical modeling described variations in O(2) and CO(2) compartmental fractions and alveolar volume. This model also included pulmonary capillary gas exchange. Experimental data were collected from measurements performed on six healthy subjects at rest and during 20, 40, 60 and 85-90% of peak V(O)(2). The correlation between the two methods was highest and the average agreement between the methods was best using 50 breaths R = 095; P model) = 1.1Q(Fick) - 2.3). The mean difference and lower to upper limits of agreement between measured and estimated data were 0.7 l/min (-2.7 to 4.1 l/min) for cardiac output; -0.9 ml/100 ml (-1.3 to -0.5 ml/100 ml) for arterial O(2) content; -0.8 ml/100 ml (-3.8 to 2.2 ml/100 ml) for mixed venous O(2) content and -0.1 ml/100 ml (-2.9 to 2.7 ml/100 ml) for arteriovenous difference O(2) content. The cardiac output estimated by the lung model was in good agreement with the direct Fick measurements in young healthy subjects.

  10. Electrophysiological Evaluation in Lumbosacral Radiculopathy

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    Seyedeh Simindokht Hosseini

    2012-07-01

    Full Text Available Background: Prevalence of electrophysiological abnormalities in patients with lumbosacral radiculopathy was evaluated.Methods: A cross-sectional study was performed on 97 consecutive patients with the clinical diagnosis of lumbosacral radiculopathy. Complete neurological examinations and standard electrophysiological evaluation was performed on the patients.Results: Patients under study had the mean age of 46.4 ± 13.1 years (mean ± standard deviation. There were positive MRI findings in 64% of the patients. In 43% L5 root and in 40% S1 root was involved. Abnormal electrophysiological findings were recorded in 82% of the patients. In patients with pretibial muscle weakness, there were significant abnormalities recorded in compound motor action potential (CMAP amplitude of the common peroneal nerve. There was significantly increased frequency of electrophysiological abnormalities in the presence of chronic clinical symptoms (P = 0.001.Conclusion: The 82% positive findings in electrophysiological studies in the diagnosis of lumbosacral radiculopathy make it an efficacious tool in the evaluation of the patients suffering from lumbosacral radiculopathy.

  11. Histotripsy for Pediatric Cardiac Applications: In Vivo Neonatal Pig Model

    Science.gov (United States)

    Miller, Ryan M.; Owens, Gabe; Ensing, Gregory; Ludomirsky, Achiau; Cain, Charles; Xu, Zhen

    2010-03-01

    This study investigated the in vivo feasibility of using histotripsy to non-invasively create a flow channel between the ventricles by generating a perforation of the ventricular septum, clinically referred to as a ventricular septum defect (VSD). The overall goal is to develop a non-invasive procedure to aid in the treatment of neonatal patients with complex congenital heart diseases such as Hypoplastic Left Heart Syndrome (HLHS). Histotripsy is a therapeutic ultrasound technique that produces mechanical fractionation of soft tissue through controlled cavitation. The study was conducted in a live and intact neonatal pig model. The ventricular septum in the neonatal pig heart was treated with histotripsy delivered by a spherically focused 1 MHz transducer positioned outside the chest wall. Histotripsy treatment was applied using 5-cycle ultrasound pulses at 1 kHz pulse repetition frequency with 12-18 MPa peak negative pressure. The treatment was guided and monitored with ultrasound imaging. In all nine subjects treated, a bubble cloud was generated on the ventricular septum using histotripsy, and visualized with ultrasound imaging. Within 20 seconds to 4 minutes following the initiation of a bubble cloud, a VSD was created in all nine pigs and confirmed by the detection of blood flow through the ventricular septum with color Doppler ultrasound. Gross morphology and histology on all hearts showed a demarcated perforation in the ventricular septum. This study shows that a VSD can be created in an intact neonatal animal using extracorporeal histotripsy under real-time ultrasound guidance.

  12. Turbulent electrical activity at sharp-edged inexcitable obstacles in a model for human cardiac tissue.

    Science.gov (United States)

    Majumder, Rupamanjari; Pandit, Rahul; Panfilov, A V

    2014-10-01

    Wave propagation around various geometric expansions, structures, and obstacles in cardiac tissue may result in the formation of unidirectional block of wave propagation and the onset of reentrant arrhythmias in the heart. Therefore, we investigated the conditions under which reentrant spiral waves can be generated by high-frequency stimulation at sharp-edged obstacles in the ten Tusscher-Noble-Noble-Panfilov (TNNP) ionic model for human cardiac tissue. We show that, in a large range of parameters that account for the conductance of major inward and outward ionic currents of the model [fast inward Na(+) current (INa), L-type slow inward Ca(2+) current (ICaL), slow delayed-rectifier current (IKs), rapid delayed-rectifier current (IKr), inward rectifier K(+) current (IK1)], the critical period necessary for spiral formation is close to the period of a spiral wave rotating in the same tissue. We also show that there is a minimal size of the obstacle for which formation of spirals is possible; this size is ∼2.5 cm and decreases with a decrease in the excitability of cardiac tissue. We show that other factors, such as the obstacle thickness and direction of wave propagation in relation to the obstacle, are of secondary importance and affect the conditions for spiral wave initiation only slightly. We also perform studies for obstacle shapes derived from experimental measurements of infarction scars and show that the formation of spiral waves there is facilitated by tissue remodeling around it. Overall, we demonstrate that the formation of reentrant sources around inexcitable obstacles is a potential mechanism for the onset of cardiac arrhythmias in the presence of a fast heart rate.

  13. Eikonal-based initiation of fibrillatory activity in thin-walled cardiac propagation models.

    Science.gov (United States)

    Herlin, Antoine; Jacquemet, Vincent

    2011-12-01

    Reentrant arrhythmias can be simulated in electrophysiological models of electrical impulse propagation governed by a reaction-diffusion system. To facilitate the initiation of a large number of independent episodes of simulated arrhythmias with controllable level of complexity, a new approach is proposed for thin-walled geometries in which depolarization wave dynamics is essentially two-dimensional. Points representing phase singularities are first randomly distributed over the epicardial surface and are assigned a topological charge (direction of rotation). A qualitatively-correct phase map is then reconstructed on the whole surface by interpolation. The eikonal-diffusion equation is used to iteratively regularize the phase map based on a priori information on wavefront propagation. An initial condition for the reaction-diffusion model is created from the resulting phase map with multiple functional/anatomical reentries. Results in an atrial model demonstrate the ability to generate statistical realizations of the same dynamics and to vary the level of complexity measured by the number of phase singularities. A library of 100 simulations with an average number of phase singularities ranging from 1 to 10 is created. An extension to volumetric patient-specific atrial models including fiber orientation and a fast conducting system is presented to illustrate possible applications.

  14. Electrophysiological properties and calcium handling of embryonic stem cell-derived cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Jae Boum Youm

    2016-03-01

    Full Text Available Embryonic stem cell-derived cardiomyocytes (ESC-CMs hold great interest in many fields of research including clinical applications such as stem cell and gene therapy for cardiac repair or regeneration. ESC-CMs are also used as a platform tool for pharmacological tests or for investigations of cardiac remodeling. ESC-CMs have many different aspects of morphology, electrophysiology, calcium handling, and bioenergetics compared with adult cardiomyocytes. They are immature in morphology, similar to sinus nodal-like in the electrophysiology, higher contribution of trans-sarcolemmal Ca2+ influx to Ca2+ handling, and higher dependence on anaerobic glycolysis. Here, I review a detailed electrophysiology and Ca2+ handling features of ESC-CMs during differentiation into adult cardiomyocytes to gain insights into how all the developmental changes are related to each other to display cardinal features of developing cardiomyocytes.

  15. Use of a Three Dimensional Printed Cardiac Model to Assess Suitability for Biventricular Repair.

    Science.gov (United States)

    Farooqi, Kanwal M; Gonzalez-Lengua, Carlos; Shenoy, Rajesh; Sanz, Javier; Nguyen, Khanh

    2016-05-01

    Three dimensional (3D) printing is rapidly gaining interest in the medical field for use in presurgical planning. We present the case of a seven-year-old boy with double outlet right ventricle who underwent a bidirectional Glenn anastomosis. We used a 3D cardiac model to assess his suitability for a biventricular repair. He underwent a left ventricle-to-aorta baffle with a right ventricle-to-pulmonary artery conduit placement. He did well postoperatively and was discharged home with no evidence of baffle obstruction and good biventricular function. A 3D printed model can provide invaluable intracardiac spatial information in these complex patients.

  16. Liénard-type models for the simulation of the action potential of cardiac nodal cells

    Science.gov (United States)

    Podziemski, P.; Żebrowski, J. J.

    2013-10-01

    Existing models of cardiac cells which include multi-variable cardiac transmembrane current are too complex to simulate the long time dynamical properties of the heart rhythm. The large number of parameters that need to be defined and set for such models make them not only cumbersome to use but also require a large computing power. Consequently, the application of such models for the bedside analysis of heart rate of a specific patient may be difficult. Other ways of modelling need to be investigated. We consider the general problem of developing a model of cardiac pacemaker tissue that allows to combine the investigation of phenomena at a time scale of thousands of heart beats with the ability to reproduce realistic tissue-level characteristics of cell dynamics. We propose a modified van der Pol-Duffing equation-a Liénard-type oscillator-as a phenomenological model for cardiac nodal tissue, with certain important physiological similarities to ion-channel models of cardiac pacemaker cells. The model presented here is specifically designed to qualitatively reproduce mesoscopic characteristics of cell dynamics, including action potential duration (APD) restitution properties, phase response characteristics, and phase space structure. We show that these characteristics agree qualitatively with the extensive ionic models and experimental results in the literature [Anumonwo et al., 1991, [33], Cao et al., 1999, [49], Coster and Celler, 2003, [31], Qu, 2004, [45], Tsalikakis et al., 2007, [32], Inada et al., 2009, [14], Qu et al., 2010, [50

  17. Ascending aortic constriction in rats for creation of pressure overload cardiac hypertrophy model.

    Science.gov (United States)

    Gs, Ajith Kumar; Raj, Binil; Santhosh, Kumar S; Sanjay, G; Kartha, Chandrasekharan Cheranellore

    2014-06-29

    Ascending aortic constriction is the most common and successful surgical model for creating pressure overload induced cardiac hypertrophy and heart failure. Here, we describe a detailed surgical procedure for creating pressure overload and cardiac hypertrophy in rats by constriction of the ascending aorta using a small metallic clip. After anesthesia, the trachea is intubated by inserting a cannula through a half way incision made between two cartilage rings of trachea. Then a skin incision is made at the level of the second intercostal space on the left chest wall and muscle layers are cleared to locate the ascending portion of aorta. The ascending aorta is constricted to 50-60% of its original diameter by application of a small sized titanium clip. Following aortic constriction, the second and third ribs are approximated with prolene sutures. The tracheal cannula is removed once spontaneous breathing was re-established. The animal is allowed to recover on the heating pad by gradually lowering anesthesia. The intensity of pressure overload created by constriction of the ascending aorta is determined by recording the pressure gradient using trans-thoracic two dimensional Doppler-echocardiography. Overall this protocol is useful to study the remodeling events and contractile properties of the heart during the gradual onset and progression from compensated cardiac hypertrophy to heart failure stage.

  18. Beyond the Mammalian Heart: Fish and Amphibians as a Model for Cardiac Repair and Regeneration

    Directory of Open Access Journals (Sweden)

    Kyle Jewhurst

    2015-12-01

    Full Text Available The epidemic of heart disease, the leading cause of death worldwide, is made worse by the fact that the adult mammalian heart is especially poor at repair. Damage to the mammal heart—such as that caused by myocardial infarction—leads to scarring, resulting in cardiac dysfunction and heart failure. In contrast, the hearts of fish and urodele amphibians are capable of complete regeneration of cardiac tissue from multiple types of damage, with full restoration of functionality. In the last decades, research has revealed a wealth of information on how these animals are able to perform this remarkable feat, and non-mammalian models of heart repair have become a burgeoning new source of data on the morphological, cellular, and molecular processes necessary to heal cardiac damage. In this review we present the major findings from recent research on the underlying mechanisms of fish and amphibian heart regeneration. We also discuss the tools and techniques that have been developed to answer these important questions.

  19. Remote delivery of congenital cardiac magnetic resonance imaging services: a unique telemedicine model.

    Science.gov (United States)

    Garg, Ruchira; Sevilla, Arnel; Garberich, Ross; Fleishman, Craig E

    2015-01-01

    Cardiac magnetic resonance imaging (CMRI) is increasingly utilized in the management of patients with congenital heart disease. Unfortunately, the expertise to perform and interpret these studies is not universally available, despite an increasing population of congenital heart survivors. This retrospective analysis describes our experience providing on-site CMRI services compared with providing the same services over a geographic distance of 250 miles. There were 83 local scans with both physician and patient on-site compared with 91 scans controlled by a physician geographically remote from the patients. The patients were well-matched for age, sex, study duration, scan type, and history of prior cardiac intervention. There was no difference in use of deep sedation or diazepam for anxiolysis, or use of atropine for arrhythmia suppression. There were no patient safety issues and there was satisfaction on the part of the referring physicians who were able to obtain more timely studies, as well as the remote-scanning physicians who had a workflow comparable with the local scans, but no lost travel time. This experience suggests that remote delivery of cardiac MRI services for the congenital heart population is feasible and can be done with comparable success and safety to a traditional "local" model. We also suggest the configuration to provide such remote CMRI services with commercially available hardware and software.

  20. Rapid development of cardiac dysfunction in a canine model of insulin resistance and moderate obesity.

    Science.gov (United States)

    Broussard, Josiane L; Nelson, Michael D; Kolka, Cathryn M; Bediako, Isaac Asare; Paszkiewicz, Rebecca L; Smith, Laura; Szczepaniak, Edward W; Stefanovski, Darko; Szczepaniak, Lidia S; Bergman, Richard N

    2016-01-01

    The worldwide incidence of obesity and diabetes continues to rise at an alarming rate. A major cause of the morbidity and mortality associated with obesity and diabetes is heart disease, yet the mechanisms that lead to cardiovascular complications remain unclear. We performed cardiac MRI to assess left ventricular morphology and function during the development of moderate obesity and insulin resistance in a well-established canine model (n = 26). To assess the influence of dietary fat composition, we randomised animals to a traditional lard diet (rich in saturated and monounsaturated fat; n = 12), a salmon oil diet (rich in polyunsaturated fat; n = 8) or a control diet (n = 6). High-fat feeding with lard increased body weight and fasting insulin and markedly reduced insulin sensitivity. Lard feeding also significantly reduced left ventricular function, evidenced by a worsening of circumferential strain and impairment in left ventricular torsion. High-fat feeding with salmon oil increased body weight; however, salmon oil feeding did not impair insulin sensitivity or cardiac function. These data emphasise the importance of dietary fat composition on both metabolic and cardiac function, and have important implications for the relationship between diet and health.

  1. Evaluation of exercise tolerance patients in cardiac rehabilitation D model based on 6 Minute Walk Test

    Directory of Open Access Journals (Sweden)

    Bielawa Lukasz.

    2012-12-01

    Full Text Available Evaluation of the results of 6-minute walk test depending on gender, age, left ventricular ejection fraction, the primary disease and BMI. Patients underwent assessment of Cardiac Rehabilitation Department in Szymbark in 2012 (80 people. Duration of rehabilitation for all patients was 21 days. The test was performed at the beginning and end of the cycle. Following the 3-week cardiac rehabilitation in the model D in a group of 80 patients with a mean age of 72 years achieved a statistically significant improvement in exercise capacity, expressed in the increase in test 6MWT distance by an average of 52 meters. In the study, men received final results statistically superior to women. The largest increase in the distance gained to patients after aortic valve prosthesis. People who are obese with a body mass index BMI over 30 have an average trip distance underperform both at baseline, final, and in the resulting increase of the distance than those with a BMI under 30. Prevention of obesity, one of the modifiable risk factors for cardiovascular disease should be the goal of training during cardiac rehabilitation patient education.

  2. Moving domain computational fluid dynamics to interface with an embryonic model of cardiac morphogenesis.

    Directory of Open Access Journals (Sweden)

    Juhyun Lee

    Full Text Available Peristaltic contraction of the embryonic heart tube produces time- and spatial-varying wall shear stress (WSS and pressure gradients (∇P across the atrioventricular (AV canal. Zebrafish (Danio rerio are a genetically tractable system to investigate cardiac morphogenesis. The use of Tg(fli1a:EGFP (y1 transgenic embryos allowed for delineation and two-dimensional reconstruction of the endocardium. This time-varying wall motion was then prescribed in a two-dimensional moving domain computational fluid dynamics (CFD model, providing new insights into spatial and temporal variations in WSS and ∇P during cardiac development. The CFD simulations were validated with particle image velocimetry (PIV across the atrioventricular (AV canal, revealing an increase in both velocities and heart rates, but a decrease in the duration of atrial systole from early to later stages. At 20-30 hours post fertilization (hpf, simulation results revealed bidirectional WSS across the AV canal in the heart tube in response to peristaltic motion of the wall. At 40-50 hpf, the tube structure undergoes cardiac looping, accompanied by a nearly 3-fold increase in WSS magnitude. At 110-120 hpf, distinct AV valve, atrium, ventricle, and bulbus arteriosus form, accompanied by incremental increases in both WSS magnitude and ∇P, but a decrease in bi-directional flow. Laminar flow develops across the AV canal at 20-30 hpf, and persists at 110-120 hpf. Reynolds numbers at the AV canal increase from 0.07±0.03 at 20-30 hpf to 0.23±0.07 at 110-120 hpf (p< 0.05, n=6, whereas Womersley numbers remain relatively unchanged from 0.11 to 0.13. Our moving domain simulations highlights hemodynamic changes in relation to cardiac morphogenesis; thereby, providing a 2-D quantitative approach to complement imaging analysis.

  3. Moving domain computational fluid dynamics to interface with an embryonic model of cardiac morphogenesis.

    Science.gov (United States)

    Lee, Juhyun; Moghadam, Mahdi Esmaily; Kung, Ethan; Cao, Hung; Beebe, Tyler; Miller, Yury; Roman, Beth L; Lien, Ching-Ling; Chi, Neil C; Marsden, Alison L; Hsiai, Tzung K

    2013-01-01

    Peristaltic contraction of the embryonic heart tube produces time- and spatial-varying wall shear stress (WSS) and pressure gradients (∇P) across the atrioventricular (AV) canal. Zebrafish (Danio rerio) are a genetically tractable system to investigate cardiac morphogenesis. The use of Tg(fli1a:EGFP) (y1) transgenic embryos allowed for delineation and two-dimensional reconstruction of the endocardium. This time-varying wall motion was then prescribed in a two-dimensional moving domain computational fluid dynamics (CFD) model, providing new insights into spatial and temporal variations in WSS and ∇P during cardiac development. The CFD simulations were validated with particle image velocimetry (PIV) across the atrioventricular (AV) canal, revealing an increase in both velocities and heart rates, but a decrease in the duration of atrial systole from early to later stages. At 20-30 hours post fertilization (hpf), simulation results revealed bidirectional WSS across the AV canal in the heart tube in response to peristaltic motion of the wall. At 40-50 hpf, the tube structure undergoes cardiac looping, accompanied by a nearly 3-fold increase in WSS magnitude. At 110-120 hpf, distinct AV valve, atrium, ventricle, and bulbus arteriosus form, accompanied by incremental increases in both WSS magnitude and ∇P, but a decrease in bi-directional flow. Laminar flow develops across the AV canal at 20-30 hpf, and persists at 110-120 hpf. Reynolds numbers at the AV canal increase from 0.07±0.03 at 20-30 hpf to 0.23±0.07 at 110-120 hpf (p< 0.05, n=6), whereas Womersley numbers remain relatively unchanged from 0.11 to 0.13. Our moving domain simulations highlights hemodynamic changes in relation to cardiac morphogenesis; thereby, providing a 2-D quantitative approach to complement imaging analysis.

  4. Noisy unmaskers of multistability of periodic rhythms in a model of the ventricular cardiac action potential

    Science.gov (United States)

    Surovyatkina, Elena; Egorchenkov, Roman; Ivanov, Guennady

    2007-06-01

    The coexistence of different dynamical regimes of cardiac cell-model at a fixed set of stimulation parameters, i.e. multistability, revealed by noise is presented in this paper. Numerical simulations are performed using Luo-Rudy (LR1) action potential model. Numerical experiments with LR1 model conducted via noisy periodical stimulation showed the coexistence of several periodic rhythms. Weak noise in period of stimulation causes a hopping process between all the (meta-) stable rhythms of cell-model. This process is reflected in several parallel branches of the bifurcation diagram: noise unveils new, invisible before, stable rhythms which could appear in this model at different initial conditions. The phenomenon of multistability is directly evidenced by other numerical experiments: we have established the multistability property of a cell consisting in the fact that different initial conditions of stimulation (different extrasystole application times) lead to different stable periodic rhythms. We have obtained the shaping of attraction basins on the action potential curves. Such basins of attraction contain a set of initial conditions which determinate a stable periodic rhythm. We have found a close association between the attraction basins of the complex rhythms on the curves of action potential and the cardiac vulnerable windows on ECG record, during which extra stimuli can induce life threatening arrhythmias. Obtained results allow us to make a conclusion that multistability is very important for the electrical conduction system of the heart from the cell level to the integrated function of the heart.

  5. Parametric study of the Noble's action potential model for cardiac Purkinje fibers

    Energy Technology Data Exchange (ETDEWEB)

    Wang, P.K.C. [Department of Electrical Engineering, University of California, Los Angeles, CA 90095-1594 (United States); Kogan, B.Y. [Department of Computer Science, University of California, Los Angeles, CA 90095-1594 (United States)]. E-mail: kogan@cs.ucla.edu

    2007-08-15

    The effect of parameter variation on repolarization processes in the Noble model (Hodjkin-Huxley type) for action potential (AP) generation in Purkinje cells is studied using a combination of computer simulation and nonlinear dynamic system theory including Hopf bifurcation analysis. Both the original Noble model and a simplified Noble model are used in this study. It is shown that these models have similar qualitative dynamic behavior in the presence of parameter variations. In particular, it is demonstrated that both normal and abnormal modes of cell performance can be obtained by varying the potassium and anion conductances. The abnormal mode (cardiac arrest) may play a significant role in disorganizing the electrical activities in the heart muscles. The existence of Hopf bifurcation with respect to variations in the anion conductance and fixed values of potassium conductances is studied in detail. The regions corresponding to spontaneous AP excitation, and various types of cardiac arrest in the ion-conductance parameter space of both full and simplified Noble models with and without external stimuli are mapped out using computer simulation.

  6. The potential impact of new generation transgenic methods on creating rabbit models of cardiac diseases.

    Science.gov (United States)

    Bősze, Z; Major, P; Baczkó, I; Odening, K E; Bodrogi, L; Hiripi, L; Varró, A

    2016-07-01

    Since the creation of the first transgenic rabbit thirty years ago, pronuclear microinjection remained the single applied method and resulted in numerous important rabbit models of human diseases, including cardiac deficiencies, albeit with low efficiency. For additive transgenesis a novel transposon mediated method, e.g., the Sleeping Beauty transgenesis, increased the efficiency, and its application to create cardiac disease models is expected in the near future. The targeted genome engineering nuclease family, e.g., the zink finger nuclease (ZFN), the transcription activator-like effector nuclease (TALEN) and the newest, clustered regularly interspaced short palindromic repeats (CRISPR) with the CRISPR associated effector protein (CAS), revolutionized the non-mouse transgenesis. The latest gene-targeting technology, the CRISPR/CAS system, was proven to be efficient in rabbit to create multi-gene knockout models. In the future, the number of tailor-made rabbit models produced with one of the above mentioned methods is expected to exponentially increase and to provide adequate models of heart diseases.

  7. Mouse atrial tumor myocytes AT-1 in cardiac electrophysiologic and pharmacologic studies%小鼠心房肌瘤AT-1细胞在心脏电生理学和药理学研究中的应用

    Institute of Scientific and Technical Information of China (English)

    杨韬

    2001-01-01

    Atrial tumor myocytes (AT-1 cells) were derived from tumor-bearing mice in which SV40 T large antigen drives atrial natriuretic promoter. AT-1 cells possess many features typically seen in cardiac cells from other species, such as spontaneous beating, multiple ion channels and responses to drugs, etc. Major ion channels are present in AT-1 cells: sodium, calcium and potassium channels. Sodium channel in AT-1 cells is highly sensitive to blocker tetrodotoxin. L- and T-type calcium channels respond to classical blockers. An important outward potassium current in AT-1 cells is the rapidly-activating delayed rectifier (IKr). IKr Is the sole time-dependently repolarizing potassium current in AT-1 cells. AT-1 cells are a very useful tool for studies in cardiac electrophysiology and pharmacology. As yet, a great number of cardiac and non-cardiac drugs have been tested for their IKr blocking actions in AT-1 cells. The polymorphic ventricular arrhythmia (torsade de pointes) is a severe side effect of IKr blockers.%小鼠心房肌瘤细胞(AT-1)系从转基因小鼠体内分化出来的一种心肌样细胞. AT-1细胞具有许多其他动物心脏细胞的典型特征,例如自发性搏动,多种离子通道和对许多药物起反应等. AT-1细胞上的主要离子通道包括钠,钙和钾通道. 钠通道对阻滞剂河豚毒高度敏感. L型和T型钙通道对典型的阻滞剂起反应. AT-1细胞上的一种重要外向钾电流是快速激活型迟缓整流外向钾电流(IKr). IKr是AT-1细胞上主要的时间依赖性复极化钾电流. 研究证明,AT-1细胞可作为心脏电生理学和药理学研究中的一种非常有用的工具. 迄今为止,在AT-1细胞上已经测试了许多心脏作用和非心脏作用药物的IKr阻滞作用. IKr阻滞药的一种严重副作用是可引起致死性的尖端扭转型室性心动过速.

  8. Distinct properties and metabolic mechanisms of postresuscitation myocardial injuries in ventricular fibrillation cardiac arrest versus asphyxiation cardiac arrest in a porcine model

    Institute of Scientific and Technical Information of China (English)

    Wu Caijun; Li Chunsheng; Zhang Yi; Yang Jun

    2014-01-01

    Background The two most prevalent causes of sudden cardiac death are ventricular fibrillation cardiac arrest (VFCA) and asphyxiation cardiac arrest (ACA).Profound postresuscitation myocardial dysfunction has been demonstrated in both VFCA and ACA animal models.Our study aimed to characterize the two porcine models of cardiac arrest and postresuscitation myocardial metabolism dysfunction.Methods Thirty-two pigs were randomized into two groups.The VFCA group (n=16) were subject to programmed electrical stimulation and the ACA group (n=16) underwent endotracheal tube clamping to induce cardiac arrest (CA).Once induced,CA remained untreated for a period of 8 minutes.Two minutes following initiation of cardiopulmonary resuscitation (CPR),defibrillation was attempted until return of spontaneous circulation (ROSC) was achieved or animals died.To assess myocardial metabolism,18F-FluoroDeoxyGlucose Positron Emission Tomography was performed at baseline and 4 hours after ROSC.Results ROSC was 100% successful in VFCA and 50% successful in ACA.VFCA had better mean arterial pressure and cardiac output after ROSC than ACA.Arterial blood gas analysis indicated more detrimental metabolic disturbances in ACA compared with VFCA after ROSC (ROSC 0.5 hours,pH:7.01±0.06 vs.7.21±0.03,P<0.01; HCO3-:(15.83±2.31 vs.20.11±1.83) mmol/L,P<0.01; lactate:(16.22±1.76 vs.5.84±1.44) mmol/L,P<0.01).Myocardial metabolism imaging using Positron Emission Tomography demonstrated that myocardial injuries after ACA were more severe and widespread than after VFCA at 4 hours after ROSC (the maximum standardized uptake value of the whole left ventricular:1.00±0.17 vs.1.93±0.27,P<0.01).Lower contents of myocardial energy metabolism enzymes (Na+-K+-ATPase enzyme activity,Ca2+-ATPase enzyme activity,superoxide dismutase and phosphodiesterase) were found in ACA relative to VFCA.Conclusions Compared with VFCA,ACA causes more severe myocardium injury and metabolism hindrance,therefore they

  9. Risk prediction models for major adverse cardiac event (MACE) following percutaneous coronary intervention (PCI): A review

    Science.gov (United States)

    Manan, Norhafizah A.; Abidin, Basir

    2015-02-01

    Five percent of patients who went through Percutaneous Coronary Intervention (PCI) experienced Major Adverse Cardiac Events (MACE) after PCI procedure. Risk prediction of MACE following a PCI procedure therefore is helpful. This work describes a review of such prediction models currently in use. Literature search was done on PubMed and SCOPUS database. Thirty literatures were found but only 4 studies were chosen based on the data used, design, and outcome of the study. Particular emphasis was given and commented on the study design, population, sample size, modeling method, predictors, outcomes, discrimination and calibration of the model. All the models had acceptable discrimination ability (C-statistics >0.7) and good calibration (Hosmer-Lameshow P-value >0.05). Most common model used was multivariate logistic regression and most popular predictor was age.

  10. Cardiac defects contribute to the pathology of spinal muscular atrophy models.

    Science.gov (United States)

    Shababi, Monir; Habibi, Javad; Yang, Hsiao T; Vale, Spencer M; Sewell, Will A; Lorson, Christian L

    2010-10-15

    Spinal muscular atrophy (SMA) is an autosomal recessive disorder, which is the leading genetic cause of infantile death. SMA is the most common inherited motor neuron disease and occurs in approximately 1:6000 live births. The gene responsible for SMA is called Survival Motor Neuron-1 (SMN1). Interestingly, a human-specific copy gene is present on the same region of chromosome 5q, called SMN2. Motor neurons are the primary tissue affected in SMA. Although it is clear that SMA is a neurodegenerative disease, there are clinical reports that suggest that other tissues contribute to the overall phenotype, especially in the most severe forms of the disease. In severe SMA cases, a growing number of congenital heart defects have been identified upon autopsy. The most common defect is a developmental defect referred to as hypoplastic left heart. The purpose of this report is to determine whether cardiac tissue is altered in SMA models and whether this could contribute to SMA pathogenesis. Here we identified early-stage developmental defects in a severe model of SMA. Additionally, pathological responses including fibrosis and oxidative stress markers were observed shortly after birth in a less severe model of disease. Similarly, functional differences were detected between wild-type and early-stage SMA animals. Collectively, this work demonstrates the importance of cardiac development and function in these severe models of SMA.

  11. Skeletal and cardiac muscle defects in a murine model of Emery-Dreifuss muscular dystrophy.

    Science.gov (United States)

    Grattan, M J; Kondo, C; Thurston, J; Alakija, P; Burke, B J; Stewart, C; Syme, D; Giles, W R

    2005-01-01

    Previous histological findings, physiological data, and behavioral observations on the A-type lamin knockout mouse (Lmna(-/-)) suggest that important aspects of this model resemble the human Emery-Dreifuss muscular dystrophy (EDMD) phenotype. The main goal of our experiments was to study skeletal and cardiac muscle function in this murine model to obtain the semiquantitative data needed for more detailed comparisons with human EDMD defects. Measurements of the mechanical properties of preparations from two different skeletal muscle groups, the soleus and the diaphragm, were made in vitro. In addition, records of the electrocardiogram, and measurements of heart rate variability were obtained; and phasic contractions (unloaded shortening) of enzymatically isolated ventricular myocytes were monitored. Soleus muscles from Lmna(-/-) mice produced less force and work than control preparations. In contrast, force and work production in strips of diaphragm were not changed significantly. Lead II electrocardiograms from conscious, restrained Lmna(-/-) mice revealed slightly decreased heart rates, with significant prolongations of PQ, QRS, and 'QT' intervals compared with those from control recordings. These ECG changes resemble some aspects of the ECG records from humans with EDMD; however, the cardiac phenotype in this Lmna(-/-) mouse model appears to be less well-defined/developed. Ventricular myocytes isolated from Lmna(-/-) mice exhibited impaired contractile responses, particularly when superfused with the beta-adrenergic agonist, isoproterenol (1 microM). This deficit was more pronounced in myocytes isolated from the left ventricle(s) than in myocytes from the right ventricle(s). In summary, tissues from the Lmna(-/-) mouse exhibit a number of skeletal and cardiac muscle deficiencies, some of which are similar to those which have been reported in studies of human EDMD.

  12. Electrophysiology in visually impaired children

    NARCIS (Netherlands)

    Genderen, Maria Michielde van

    2006-01-01

    Inherited retinal disorders and posterior visual pathway abnormalities are important causes of visual impairment in children. Visual electrophysiology often is indispensable in diagnosing these conditions. This thesis shows the wide range of use of pediatric electro-ophthalmology, and demonstrates i

  13. Impact of thoracic surgery on cardiac morphology and function in small animal models of heart disease: a cardiac MRI study in rats.

    Directory of Open Access Journals (Sweden)

    Peter Nordbeck

    Full Text Available BACKGROUND: Surgical procedures in small animal models of heart disease might evoke alterations in cardiac morphology and function. The aim of this study was to reveal and quantify such potential artificial early or long term effects in vivo, which might account for a significant bias in basic cardiovascular research, and, therefore, could potentially question the meaning of respective studies. METHODS: Female Wistar rats (n = 6 per group were matched for weight and assorted for sham left coronary artery ligation or control. Cardiac morphology and function was then investigated in vivo by cine magnetic resonance imaging at 7 Tesla 1 and 8 weeks after the surgical procedure. The time course of metabolic and inflammatory blood parameters was determined in addition. RESULTS: Compared to healthy controls, rats after sham surgery showed a lower body weight both 1 week (267.5±10.6 vs. 317.0±11.3 g, n<0.05 and 8 weeks (317.0±21.1 vs. 358.7±22.4 g, n<0.05 after the intervention. Left and right ventricular morphology and function were not different in absolute measures in both groups 1 week after surgery. However, there was a confined difference in several cardiac parameters normalized to the body weight (bw, such as myocardial mass (2.19±0.30/0.83±0.13 vs. 1.85±0.22/0.70±0.07 mg left/right per g bw, p<0.05, or enddiastolic ventricular volume (1.31±0.36/1.21±0.31 vs. 1.14±0.20/1.07±0.17 µl left/right per g bw, p<0.05. Vice versa, after 8 weeks, cardiac masses, volumes, and output showed a trend for lower values in sham operated rats compared to controls in absolute measures (782.2±57.2/260.2±33.2 vs. 805.9±84.8/310.4±48.5 mg, p<0.05 for left/right ventricular mass, but not normalized to body weight. Matching these findings, blood testing revealed only minor inflammatory but prolonged metabolic changes after surgery not related to cardiac disease. CONCLUSION: Cardio-thoracic surgical procedures in experimental myocardial infarction

  14. Accelerating PS model-based dynamic cardiac MRI using compressed sensing.

    Science.gov (United States)

    Zhang, Xiaoyong; Xie, Guoxi; Shi, Caiyun; Su, Shi; Zhang, Yongqin; Liu, Xin; Qiu, Bensheng

    2016-02-01

    High spatiotemporal resolution MRI is a challenging topic in dynamic MRI field. Partial separability (PS) model has been successfully applied to dynamic cardiac MRI by exploiting data redundancy. However, the model requires substantial preprocessing data to accurately estimate the model parameters before image reconstruction. Since compressed sensing (CS) is a potential technique to accelerate MRI by reducing the number of acquired data, the combination of PS and CS, named as Stepped-SparsePS, was introduced to accelerate the preprocessing data acquisition of PS in this work. The proposed Stepped-SparsePS method sequentially reconstructs a set of aliased dynamic images in each channel based on PS model and then the final dynamic images from the aliased images using CS. The results from numerical simulations and in vivo experiments demonstrate that Stepped-SparsePS could significantly reduce data acquisition time while preserving high spatiotemporal resolution. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Influence of cardiac tissue anisotropy on re-entrant activation in computational models of ventricular fibrillation

    Science.gov (United States)

    Clayton, Richard H.

    2009-06-01

    The aim of this study was to establish the role played by anisotropic diffusion in (i) the number of filaments and epicardial phase singularities that sustain ventricular fibrillation in the heart, (ii) the lifetimes of filaments and phase singularities, and (iii) the creation and annihilation dynamics of filaments and phase singularities. A simplified monodomain model of cardiac tissue was used, with membrane excitation described by a simplified 3-variable model. The model was configured so that a single re-entrant wave was unstable, and fragmented into multiple re-entrant waves. Re-entry was then initiated in tissue slabs with varying anisotropy ratio. The main findings of this computational study are: (i) anisotropy ratio influenced the number of filaments sustaining simulated ventricular fibrillation, with more filaments present in simulations with smaller values of transverse diffusion coefficient, (ii) each re-entrant filament was associated with around 0.9 phase singularities on the surface of the slab geometry, (iii) phase singularities were longer lived than filaments, and (iv) the creation and annihilation of filaments and phase singularities were linear functions of the number of filaments and phase singularities, and these relationships were independent of the anisotropy ratio. This study underscores the important role played by tissue anisotropy in cardiac ventricular fibrillation.

  16. Risk Factor Analyses for the Return of Spontaneous Circulation in the Asphyxiation Cardiac Arrest Porcine Model

    Directory of Open Access Journals (Sweden)

    Cai-Jun Wu

    2015-01-01

    Full Text Available Background: Animal models of asphyxiation cardiac arrest (ACA are frequently used in basic research to mirror the clinical course of cardiac arrest (CA. The rates of the return of spontaneous circulation (ROSC in ACA animal models are lower than those from studies that have utilized ventricular fibrillation (VF animal models. The purpose of this study was to characterize the factors associated with the ROSC in the ACA porcine model. Methods: Forty-eight healthy miniature pigs underwent endotracheal tube clamping to induce CA. Once induced, CA was maintained untreated for a period of 8 min. Two minutes following the initiation of cardiopulmonary resuscitation (CPR, defibrillation was attempted until ROSC was achieved or the animal died. To assess the factors associated with ROSC in this CA model, logistic regression analyses were performed to analyze gender, the time of preparation, the amplitude spectrum area (AMSA from the beginning of CPR and the pH at the beginning of CPR. A receiver-operating characteristic (ROC curve was used to evaluate the predictive value of AMSA for ROSC. Results: ROSC was only 52.1% successful in this ACA porcine model. The multivariate logistic regression analyses revealed that ROSC significantly depended on the time of preparation, AMSA at the beginning of CPR and pH at the beginning of CPR. The area under the ROC curve in for AMSA at the beginning of CPR was 0.878 successful in predicting ROSC (95% confidence intervals: 0.773∼0.983, and the optimum cut-off value was 15.62 (specificity 95.7% and sensitivity 80.0%. Conclusions: The time of preparation, AMSA and the pH at the beginning of CPR were associated with ROSC in this ACA porcine model. AMSA also predicted the likelihood of ROSC in this ACA animal model.

  17. Cardiac tissue structure. Electric field interactions in polarizing the heart: 3D computer models and applications

    Science.gov (United States)

    Entcheva, Emilia

    1998-11-01

    The goal of this research is to investigate the interactions between the cardiac tissue structure and applied electric fields in producing complex polarization patterns. It is hypothesized that the response of the heart in the conditions of strong electric shocks, as those applied in defibrillation, is dominated by mechanisms involving the cardiac muscle structure perceived as a continuum. Analysis is carried out in three-dimensional models of the heart with detailed fiber architecture. Shock-induced transmembrane potentials are calculated using the bidomain model in its finite element implementation. The major new findings of this study can be summarized as follows: (1) The mechanisms of polarization due to cardiac fiber curvature and fiber rotation are elucidated in three-dimensional ellipsoidal hearts of variable geometry; (2) Results are presented showing that the axis of stimulation and the polarization axis on a whole heart level might differ significantly due to geometric and anisotropic factors; (3) Virtual electrode patterns are demonstrated numerically inside the ventricular wall in internal defibrillation conditions. The role of the tissue-bath interface in shaping the shock-induced polarization is revealed; (4) The generation of 3D phase singularity scrolls by shock-induced intramural virtual electrode patterns is proposed as evidence for a possible new mechanism for the failure to defibrillate. The results of this study emphasize the role of unequal anisotropy in the intra- and extracellular domains, as well as the salient fiber architecture characteristics, such as curvature and transmural rotation, in polarizing the myocardium. Experimental support of the above findings was actively sought and found in recent optical mapping studies using voltage-sensitive dyes. If validated in vivo, these findings would significantly enrich the prevailing concepts about the mechanisms of stimulation and defibrillation of the heart.

  18. Electrophysiologic and cellular characteristics of cardiomyocytes after X-ray irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Frieß, Johannes L., E-mail: johannes.friess@h-ab.de [University for Applied Sciences Aschaffenburg, biomems lab, Würzburger Straße 45, 63743 Aschaffenburg (Germany); Heselich, Anja [Technische Universität Darmstadt, Developmental Biology and Neurogenetics, Schnittspahnstraße 13, 64287 Darmstadt (Germany); Ritter, Sylvia [Helmholtz Institute for Heavy Ion Research (GSI), Biophysics Department, Planckstraße 1, 64291 Darmstadt (Germany); Haber, Angelina; Kaiser, Nicole; Layer, Paul G. [Technische Universität Darmstadt, Developmental Biology and Neurogenetics, Schnittspahnstraße 13, 64287 Darmstadt (Germany); Thielemann, Christiane [University for Applied Sciences Aschaffenburg, biomems lab, Würzburger Straße 45, 63743 Aschaffenburg (Germany)

    2015-07-15

    Highlights: • Electrophysiologic and cellular effects of X-rays on primary cardiac cell cultures. • X-ray doses between 0.5 and 7 Gy. • Higher beat rate at reduced field action potential durations 7 days after exposure. • More increased cell cycle checkpoint arrest in G2/M than in G1/S phase. • Induced DSBs were mostly repaired within 24 h after irradiation. - Abstract: The aim of this study was to investigate possible effects of ionizing irradiation on the electrophysiological functionality of cardiac myocytes in vitro. Primary chicken cardiomyocytes with spontaneous beating activity were irradiated with X-rays (dose range of 0.5–7 Gy). Functional alterations of cardiac cell cultures were evaluated up to 7 days after irradiation using microelectrode arrays. As examined endpoints, cell proliferation, apoptosis, reactive oxygen species (ROS) and DNA damage were evaluated. The beat rate of the cardiac networks increased in a dose-dependent manner over one week. The duration of single action potentials was slightly shortened. Additionally, we observed lower numbers of mitotic and S-phase cells at certain time points after irradiation. Also, the number of cells with γH2AX foci increased as a function of the dose. No significant changes in the level of ROS were detected. Induction of apoptosis was generally negligibly low. This is the first report to directly show alterations in cardiac electrophysiology caused by ionizing radiation, which were detectable up to one week after irradiation.

  19. Hypoxic neuropathy versus diabetic neuropathy : an electrophysiological study in rats

    NARCIS (Netherlands)

    Gispen, W.H.; Hendriksen, P.H.; Oey, P.L.; Wieneke, G.H.; Huffelen, A.C. van

    1992-01-01

    In the experimental rat model of diabetes a slowing of nerve conduction velocity and a resistance to ischemic conduction failure have been found as an indication of polyneuropathy. The same electrophysiological abnormalities have been demonstrated in a model in which healthy rats are kept under hypo

  20. The forward and inverse problem of cardiac magnetic fields based on concentric ellipsoid torso-heart model

    Science.gov (United States)

    Wang, Qian; Hua, Ning; Tang, Xue-Zheng; Lu, Hong; Ma, Ping; Tang, Fa-Kuan

    2010-08-01

    This paper constructs a concentric ellipsoid torso-heart model by boundary element method and investigates the impacts of model structures on the cardiac magnetic fields generated by both equivalent primary source-a current dipole and volume currents. Then by using the simulated magnetic fields based on the torso-heart model as input, the cardiac current sources-an array of current dipoles by optimal constrained linear inverse method are constructed. Next, the current dipole array reconstruction considering boundaries are compared with that in an unbounded homogeneous medium. Furthermore, the influence of random noise on reconstruction is also considered and the reconstructing effect is judged by several reconstructing parameters.

  1. Noise-induced ectopic activity in a simple cardiac cell model

    Science.gov (United States)

    Hastings, Harold

    2005-03-01

    Ectopic activity in the form of premature ventricular contractions (PVCs) is relatively common in the normal heart. Although PVCs are normally harmless, sometimes but rarely PVCs can generate spiral waves of activation through interaction with other waves of activation, potentially progressing to ventricular tachycardia, followed by ventricular fibrillation and sudden cardiac death. Clusters of PVCs have been found to be significantly more dangerous than isolated PVCs. We model PVC generation by applying triggers (noise) to the generic FitzHugh-Nagumo model as substrate, and study the effects the noise level and excitability. We find: exponential waiting time behavior at fixed parameter levels; no evidence of clustering at fixed parameter levels; and a sharp increase in PVCs as excitability approaches the auto-oscillatory threshold or noise increases beyond a similar threshold. This produces sharp increases in theoretical rates of PVC-induced fibrillation, consistent with results of A Gelzer et al. in animal models. Partially supported by the NSF and NIH.

  2. Association of ADAMTS-7 Levels with Cardiac Function in a Rat Model of Acute Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Wenjing Wu

    2016-03-01

    Full Text Available Background/Aims: High ADAMTS-7 levels are associated with acute myocardial infarction (AMI, although its involvement in ventricular remodeling is unclear. In this study, we investigated the association between ADAMTS-7 expression and cardiac function in a rat AMI model. Methods: Sprague-Dawley rats were randomized into AMI (n = 40 and sham (n = 20 groups. The left anterior descending artery was sutured to model AMI. Before surgery and 7, 14, 28, and 42 days post-surgery, ADAMTS-7 and brain natriuretic peptide (BNP, and cartilage oligomeric matrix protein (COMP were assessed by ELISA, western blot, real-time RT-PCR, and/or immunohistochemistry. Cardiac functional and structural parameters were assessed by M-mode echocardiography. Results: After AMI, plasma ADAMTS-7 levels increased, peaking on day 28 (AMI: 13.2 ± 6.3 vs. sham: 3.4 ± 1.3 ng/ml, P P = 0.025, left ventricular end-diastolic diameter (r = 0.695, P = 0.041, left ventricular end-systolic diameter (r = 0.710, P = 0.039, left ventricular ejection fraction (r = 0.695, P = 0.036, and left ventricular short-axis fractional shortening (r = 0.721, P = 0.024. Conclusions: ADAMTS-7 levels may reflect the degree of ventricular remodeling after AMI.

  3. Enhanced currents through L-type calcium channels in cardiomyocytes disturb the electrophysiology of the dystrophic heart.

    Science.gov (United States)

    Koenig, Xaver; Rubi, Lena; Obermair, Gerald J; Cervenka, Rene; Dang, Xuan B; Lukacs, Peter; Kummer, Stefan; Bittner, Reginald E; Kubista, Helmut; Todt, Hannes; Hilber, Karlheinz

    2014-02-15

    Duchenne muscular dystrophy (DMD), induced by mutations in the gene encoding for the cytoskeletal protein dystrophin, is an inherited disease characterized by progressive muscle weakness. Besides the relatively well characterized skeletal muscle degenerative processes, DMD is also associated with cardiac complications. These include cardiomyopathy development and cardiac arrhythmias. The current understanding of the pathomechanisms in the heart is very limited, but recent research indicates that dysfunctional ion channels in dystrophic cardiomyocytes play a role. The aim of the present study was to characterize abnormalities in L-type calcium channel function in adult dystrophic ventricular cardiomyocytes. By using the whole cell patch-clamp technique, the properties of currents through calcium channels in ventricular cardiomyocytes isolated from the hearts of normal and dystrophic adult mice were compared. Besides the commonly used dystrophin-deficient mdx mouse model for human DMD, we also used mdx-utr mice, which are both dystrophin- and utrophin-deficient. We found that calcium channel currents were significantly increased, and channel inactivation was reduced in dystrophic cardiomyocytes. Both effects enhance the calcium influx during an action potential (AP). Whereas the AP in dystrophic mouse cardiomyocytes was nearly normal, implementation of the enhanced dystrophic calcium conductance in a computer model of a human ventricular cardiomyocyte considerably prolonged the AP. Finally, the described dystrophic calcium channel abnormalities entailed alterations in the electrocardiograms of dystrophic mice. We conclude that gain of function in cardiac L-type calcium channels may disturb the electrophysiology of the dystrophic heart and thereby cause arrhythmias.

  4. Doxycycline attenuates protein aggregation in cardiomyocytes and improves survival of a mouse model of cardiac proteinopathy.

    Science.gov (United States)

    Zheng, Hanqiao; Tang, Mingxin; Zheng, Qingwen; Kumarapeli, Asangi R K; Horak, Kathleen M; Tian, Zongwen; Wang, Xuejun

    2010-10-19

    The goal of this pre-clinical study was to assess the therapeutic efficacy of doxycycline (Doxy) for desmin-related cardiomyopathy (DRC) and to elucidate the potential mechanisms involved. DRC, exemplifying cardiac proteinopathy, is characterized by intrasarcoplasmic protein aggregation and cardiac insufficiency. No effective treatment for DRC is available presently. Doxy was shown to attenuate aberrant intranuclear aggregation and toxicity of misfolded proteins in noncardiac cells and animal models of other proteinopathies. Mice and cultured neonatal rat cardiomyocytes with transgenic (TG) expression of a human DRC-linked missense mutation R120G of αB-crystallin (CryAB(R120G)) were used for testing the effect of Doxy. Doxy was administered via drinking water (6 mg/ml) initiated at 8 or 16 weeks of age. Doxy treatment initiated at 16 weeks of age significantly delayed the premature death of CryAB(R120G) TG mice, with a median lifespan of 30.4 weeks (placebo group, 25 weeks; p Doxy treatment initiated at 8 weeks of age significantly attenuated cardiac hypertrophy in 1 month. Further investigation revealed that Doxy significantly reduced the abundance of CryAB-positive microscopic aggregates, detergent-resistant CryAB oligomers, and total ubiquitinated proteins in CryAB(R120G) TG hearts. In cell culture, Doxy treatment dose-dependently suppressed the formation of both microscopic protein aggregates and detergent-resistant soluble CryAB(R120G) oligomers and reversed the up-regulation of p62 protein induced by adenovirus-mediated CryAB(R120G) expression. Doxy suppresses CryAB(R120G)-induced aberrant protein aggregation in cardiomyocytes and prolongs CryAB(R120G)-based DRC mouse survival. Copyright © 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  5. N-acetylcysteine attenuates the development of cardiac fibrosis and remodeling in a mouse model of heart failure.

    Science.gov (United States)

    Giam, Beverly; Chu, Po-Yin; Kuruppu, Sanjaya; Smith, A Ian; Horlock, Duncan; Kiriazis, Helen; Du, Xiao-Jun; Kaye, David M; Rajapakse, Niwanthi W

    2016-04-01

    Oxidative stress plays a central role in the pathogenesis of heart failure. We aimed to determine whether the antioxidantN-acetylcysteine can attenuate cardiac fibrosis and remodeling in a mouse model of heart failure. Minipumps were implanted subcutaneously in wild-type mice (n = 20) and mice with cardiomyopathy secondary to cardiac specific overexpression of mammalian sterile 20-like kinase 1 (MST-1;n = 18) to administerN-acetylcysteine (40 mg/kg per day) or saline for a period of 8 weeks. At the end of this period, cardiac remodeling and function was assessed via echocardiography. Fibrosis, oxidative stress, and expression of collagen types I andIIIwere quantified in heart tissues. Cardiac perivascular and interstitial fibrosis were greater by 114% and 209%, respectively, inMST-1 compared to wild type (P ≤ 0.001). InMST-1 mice administeredN-acetylcysteine, perivascular and interstitial fibrosis were 40% and 57% less, respectively, compared to those treated with saline (P ≤ 0. 03). Cardiac oxidative stress was 119% greater inMST-1 than in wild type (P cardiac fibrosis and related remodeling in the setting of heart failure potentially by reducing oxidative stress. This study provides the basis to investigate the role ofN-acetylcysteine in chronic heart failure.

  6. Identifying cardiac syncope based on clinical history: a literature-based model tested in four independent datasets.

    Directory of Open Access Journals (Sweden)

    Janneke Berecki-Gisolf

    Full Text Available BACKGROUND: We aimed to develop and test a literature-based model for symptoms that associate with cardiac causes of syncope. METHODS AND RESULTS: Seven studies (the derivation sample reporting ≥2 predictors of cardiac syncope were identified (4 Italian, 1 Swiss, 1 Canadian, and 1 from the United States. From these, 10 criteria were identified as diagnostic predictors. The conditional probability of each predictor was calculated by summation of the reported frequencies. A model of conditional probabilities and a priori probabilities of cardiac syncope was constructed. The model was tested in four datasets of patients with syncope (the test sample from Calgary (n=670; 21% had cardiac syncope, Amsterdam (n=503; 9%, Milan (n=689; 5% and Rochester (3877; 11%. In the derivation sample ten variables were significantly associated with cardiac syncope: age, gender, structural heart disease, low number of spells, brief or absent prodrome, supine syncope, effort syncope, and absence of nausea, diaphoresis and blurred vision. Fitting the test datasets to the full model gave C-statistics of 0.87 (Calgary, 0.84 (Amsterdam, 0.72 (Milan and 0.71 (Rochester. Model sensitivity and specificity were 92% and 68% for Calgary, 86% and 67% for Amsterdam, 76% and 59% for Milan, and 73% and 52% for Rochester. A model with 5 variables (age, gender, structural heart disease, low number of spells, and lack of prodromal symptoms was as accurate as the total set. CONCLUSION: A simple literature-based Bayesian model of historical criteria can distinguish patients with cardiac syncope from other patients with syncope with moderate accuracy.

  7. Relative acceleration approach for conduction failure of cardiac excitation propagation on anisotropic curved surfaces

    CERN Document Server

    Chun, Sehun

    2012-01-01

    In cardiac electrophysiology, it is important to predict the necessary conditions for conduction failure, the failure of the cardiac excitation propagation even in the presence of normal excitable tissue, in high-dimensional anisotropic space because these conditions may provide feasible mechanisms for abnormal excitation propagations such as atrial re-entry and, subsequently, atrial fibrillation even without taking into account the time-dependent refractory region. Some conditions of conduction failure have been studied for anisotropy or simple curved surfaces, but the general conditions on anisotropic curved surfaces (anisotropic and curved surface) remain unknown. To predict and analyze conduction failure on anisotropic curved surfaces, a new analytic approach is proposed, called the relative acceleration approach borrowed from spacetime physics. Motivated by a discrete model of cardiac excitation propagation, this approach is based on the hypothesis that a large relative acceleration can translate to a dr...

  8. Integral-based identification of patient specific parameters for a minimal cardiac model.

    Science.gov (United States)

    Hann, C E; Chase, J G; Shaw, G M

    2006-02-01

    A minimal cardiac model has been developed which accurately captures the essential dynamics of the cardiovascular system (CVS). However, identifying patient specific parameters with the limited measurements often available, hinders the clinical application of the model for diagnosis and therapy selection. This paper presents an integral-based parameter identification method for fast, accurate identification of patient specific parameters using limited measured data. The integral method turns a previously non-linear and non-convex optimization problem into a linear and convex identification problem. The model includes ventricular interaction and physiological valve dynamics. A healthy human state and four disease states, valvular stenosis, pulmonary embolism, cardiogenic shock and septic shock are used to test the method. Parameters for the healthy and disease states are accurately identified using only discretized flows into and out of the two cardiac chambers, the minimum and maximum volumes of the left and right ventricles, and the pressure waveforms through the aorta and pulmonary artery. These input values can be readily obtained non-invasively using echo-cardiography and ultra-sound, or invasively via catheters that are often used in Intensive Care. The method enables rapid identification of model parameters to match a particular patient condition in clinical real time (3-5 min) to within a mean value of 4-10% in the presence of 5-15% uniformly distributed measurement noise. The specific changes made to simulate each disease state are correctly identified in each case to within 10% without false identification of any other patient specific parameters. Clinically, the resulting patient specific model can then be used to assist medical staff in understanding, diagnosis and treatment selection.

  9. Electrophysiological findings in Rasmussen's syndrome.

    Science.gov (United States)

    Gündüz, Ayşegül; Kızıltan, Meral E; Coşkun, Tülin; Delil, Şakir; Yeni, Naz; Özkara, Çiğdem

    2016-03-01

    Rasmussen syndrome is a rare, inflammatory and probably autoimmune disease presenting with epilepsia partialis continua which is generally in the form of myoclonic jerks and involves the upper extremities with or without head involvement. We sought to demonstrate the electrophysiological features in patients with Rasmussen syndrome. We performed continuous electrophysiological recordings of involuntary movement, as well as recordings of startle responses and long latency reflex in three patients with a diagnosis of Rasmussen syndrome. Positive and negative myoclonus were recorded. Startle responses were found to be suppressed. However, long latency reflexes were high in amplitude and one patient even had a C reflex. Stimulus-sensitive positive and negative cortical myoclonus are typical in epilepsia partialis continua of Rasmussen syndrome and degeneration of brainstem and reticulospinal pathways may develop in Rasmussen syndrome.

  10. Assessment of the cellular and electrophysiological response of cardiomyocytes to radiation

    Science.gov (United States)

    Helm, Alexander; Ritter, Sylvia; Durante, Marco; Friess, Johannes; Thielemann, Christiane; Mr; Frank, Simon

    Cardiac disease is considered as a late effect resulting from an exposure during long-term space missions. Yet, the underlying mechanisms and the impact of radiation quality and dose are not well understood. To address this topic, we used cardiomyocytes derived from mouse embryonic stem cells (mESC) as a model system. This model has already been successfully used for cardiotoxicity screening of new drugs. Both, the cellular and electrophysiological response to X-ray irradiation were examined. Cellular endpoints such as the induction of micronuclei, apoptosis, number of binucleated cells and expression of connexin43 (Cx 43) were analyzed by standard techniques. For electrophysiological studies a microelectrode array (MEA) was used allowing non-invasive recordings of electrical signals such as signal amplitude and shape, beat rate and conduction velocity. Data analysis was performed using the MATLAB based software DrCell. As a first approach, cardiomyocytes were generated by differentiation of mESC via the formation of embryoid bodies. However, the system proved to be unsuitable due to large intra- and inter-sample variations. In consecutive experiments we used commercially available Cor.At cells, i.e. a pure culture of mESC derived cardiomyocytes. For the analysis of cellular and electrophysiological endpoints Cor.At cells were seeded onto chamber slides or MEA chips, respectively. Irradiation with 0.5 and 2 Gy X-rays (250 kV, 16 mA) was performed two days after seeding. At that time cardiomyocytes are electrically coupled through gap junctions and form a spontaneously beating network. Samples were examined up to four days after exposure. Analysis of the electrophysiological data revealed only minor differences between controls and X-irradiated samples indicating the functionality of cardiomyocytes is not within the dose range examined. Currently, further experiments are performed to statistically verify this finding. Additionally, the expression of Cx 43, a major

  11. The electrophysiology of spinocerebellar ataxias.

    Science.gov (United States)

    Liang, Lipin; Chen, Tao; Wu, Yan

    2016-02-01

    Spinocerebellar Ataxias (SCAs) are a group of autosomal dominantly inherited neurodegenerative diseases, involving the cerebellum and the brainstem. Genetic testing is the most important method of diagnosis. Nowadays, nearly 40 types of SCAs have been identified by genetic analysis. Peripheral nerve impairment is common in SCAs: electrophysiological examination of SCA1, SCA2 and SCA3 usually shows sensorimotor and sensory neuropathy, while pure motor neuropathy is more rare, being seen only in SCA2. The abnormal VEP of SCA1, SCA2 and SCA3 include prolonged P100 latencies and reduced P100 amplitudes. Abnormal BAEP involves prolonged interpeak latency of I-III and III-V. Abnormal SEP usually show absent P40 wave and prolonged P40 latency. The abnormal MEP usually shows prolonged central motor conduction time or absent responses. SCA2 is not associated with gaze-evoked nystagmus and dysmetric saccades. SCA3 usually presents as saccadic intrusions and oscillations. Whether peripheral nerves are involved in SCA6 is uncertain; although abnormal electrophysiology has been reported, neuropathological examinations have not found degenerative changes or reductions in the number of neurons in the anterior horns and/or dorsal root ganglia in SCA6. It is therefore hypothesized that this might be a displayed feature of axonopathy. The clinical presentation of most cases of SCA6 includes spontaneous and positional downbeat nystagmus, and perverted head-shaking nystagmus. Opinion about peripheral nerve involvement in SCA7 varies between authors. Losing P100 is a predominant feature of SCA7, while III and IV/V wave absence is common in SCA17. Electrophysiological study of other types is currently limited, requiring large-scale studies for confirmation. Similar and overlapping clinical features make it difficult to differentiate each type. Electrophysiological testing can therefore play an important role in helping to identify the common phenotypes of SCAs, and determine the extent

  12. Reconstructing patient-specific cardiac models from contours via Delaunay triangulation and graph-cuts.

    Science.gov (United States)

    Wan, Min; Lim, Calvin; Zhang, Junmei; Su, Yi; Yeo, Si Yong; Wang, Desheng; Tan, Ru San; Zhong, Liang

    2013-01-01

    This study proposes a novel method to reconstruct the left cardiac structure from contours. Given the contours representing left ventricle (LV), left atrium (LA), and aorta (AO), re-orientation, contour matching, extrapolation, and interpolation are performed sequentially. The processed data are then reconstructed via a variational method. The weighted minimal surface model is revised to handle the multi-phase cases, which happens at the LV-LA-AO junction. A Delaunay-based tetrahedral mesh is generated to discretize the domain while the max-flow/min-cut algorithm is utilized as the minimization tool. The reconstructed model including LV, LA, and AO structure is extracted from the mesh and post-processed further. Numerical examples show the robustness and effectiveness of the proposed method.

  13. Unstable spiral waves and local Euclidean symmetry in a model of cardiac tissue

    Energy Technology Data Exchange (ETDEWEB)

    Marcotte, Christopher D.; Grigoriev, Roman O. [School of Physics, Georgia Institute of Technology, Atlanta, Georgia 30332 (United States)

    2015-06-15

    This paper investigates the properties of unstable single-spiral wave solutions arising in the Karma model of two-dimensional cardiac tissue. In particular, we discuss how such solutions can be computed numerically on domains of arbitrary shape and study how their stability, rotational frequency, and spatial drift depend on the size of the domain as well as the position of the spiral core with respect to the boundaries. We also discuss how the breaking of local Euclidean symmetry due to finite size effects as well as the spatial discretization of the model is reflected in the structure and dynamics of spiral waves. This analysis allows identification of a self-sustaining process responsible for maintaining the state of spiral chaos featuring multiple interacting spirals.

  14. Hypothermia ameliorates gastrointestinal ischemic injury sustained in a porcine cardiac arrest model

    Institute of Scientific and Technical Information of China (English)

    LU Yi; WANG Shuo; LI Chun-sheng

    2012-01-01

    Background During cardiac arrest,the gastrointestinal tract is sensitive to ischemia.Protection of the gastrointestinal tract is a critical factor in determining prognosis following cardiopulmonary resuscitation (CPR).This study seeks to determine the extent of gastrointestinal tract injury and the potential protective effect of inducing hypothermia following a porcine cardiac arrest model and CPR.Methods Ventricular fibrillation was induced by programmed electrical stimulation in 16 male domestic pigs (n=8 per group).Four minutes after ventricular fibrillation,CPR was performed.Pigs that successfully restored spontaneous circulation then received intravenous infusions of saline at either 4C or room temperature to produce hypothermic and control conditions respectively.Serum diamine oxidase and gastrointestinal adenosine triphosphate enzyme activity were determined and histopathology of the gastrointestinal tract was performed by light microscopy and electron microscopy.Results Significant injury of the gastrointestinal tract after CPR was found.Na+-K+ and Ca2+ adenosine triphosphate enzyme activity in the gastric tissue were significantly high in animals receiving hypothermia treatment compared to controls.Hypothermia also significantly reduced serum diamine oxidase after CPR compared to the control group.Moreover,severe injury sustained by the gastrointestinal tissue was significantly ameliorated under hypothermic conditions compared to controls.Conclusions Gastrointestinal injury and abnormal energy metabolism are strikingly evident following CPR.Hypothermia,which is induced by an infusion of 4C saline,can rapidly reduce internal body temperature,improve energy metabolism,and ameliorate injury to the gastrointestinal mucosa after CPR.

  15. High-fat Diet Promotes Cardiac Remodeling in an Experimental Model of Obesity

    Directory of Open Access Journals (Sweden)

    Fernando Martins

    2015-01-01

    Full Text Available AbstractBackground:Although nutritional, metabolic and cardiovascular abnormalities are commonly seen in experimental studies of obesity, it is uncertain whether these effects result from the treatment or from body adiposity.Objective:To evaluate the influence of treatment and body composition on metabolic and cardiovascular aspects in rats receiving high saturated fat diet.Methods:Sixteen Wistar rats were used, distributed into two groups, the control (C group, treated with isocaloric diet (2.93 kcal/g and an obese (OB group, treated with high-fat diet (3.64 kcal/g. The study period was 20 weeks. Analyses of nutritional behavior, body composition, glycemia, cholesterolemia, lipemia, systolic arterial pressure, echocardiography, and cardiac histology were performed.Results:High-fat diet associates with manifestations of obesity, accompanied by changes in glycemia, cardiomyocyte hypertrophy, and myocardial interstitial fibrosis. After adjusting for adiposity, the metabolic effects were normalized, whereas differences in morphometric changes between groups were maintained.Conclusion:It was concluded that adiposity body composition has a stronger association with metabolic disturbances in obese rodents, whereas the high-fat dietary intervention is found to be more related to cardiac morphological changes in experimental models of diet-induced obesity.

  16. Adaptation of cardiac structure by mechanical feedback in the environment of the cell: a model study.

    Science.gov (United States)

    Arts, T; Prinzen, F W; Snoeckx, L H; Rijcken, J M; Reneman, R S

    1994-01-01

    In the cardiac left ventricle during systole mechanical load of the myocardial fibers is distributed uniformly. A mechanism is proposed by which control of mechanical load is distributed over many individual control units acting in the environment of the cell. The mechanics of the equatorial region of the left ventricle was modeled by a thick-walled cylinder composed of 6-1500 shells of myocardial fiber material. In each shell a separate control unit was simulated. The direction of the cells was varied so that systolic fiber shortening approached a given optimum of 15%. End-diastolic sarcomere length was maintained at 2.1 microns. Regional early-systolic stretch and global contractility stimulated growth of cellular mass. If systolic shortening was more than normal the passive extracellular matrix stretched. The design of the load-controlling mechanism was derived from biological experiments showing that cellular processes are sensitive to mechanical deformation. After simulating a few hundred adaptation cycles, the macroscopic anatomical arrangement of helical pathways of the myocardial fibers formed automatically. If pump load of the ventricle was changed, wall thickness and cavity volume adapted physiologically. We propose that the cardiac anatomy may be defined and maintained by a multitude of control units for mechanical load, each acting in the cellular environment. Interestingly, feedback through fiber stress is not a compelling condition for such control. PMID:8038399

  17. Beneficial effects of schisandrin B on the cardiac function in mice model of myocardial infarction.

    Science.gov (United States)

    Chen, Pengsheng; Pang, Sisi; Yang, Naiquan; Meng, Haoyu; Liu, Jia; Zhou, Ningtian; Zhang, Min; Xu, Zhihui; Gao, Wei; Chen, Bo; Tao, Zhengxian; Wang, Liansheng; Yang, Zhijian

    2013-01-01

    The fruit of Schisandra chinensis has been used in the traditional Chinese medicine for thousands of years. Accumulating evidence suggests that Schisandrin B (Sch B) has cardioprotection effect on myocardial ischemia in vitro. However, it is unclear whether Sch B has beneficial effects on continuous myocardial ischemia in vivo. The aim of the present study was to investigate whether Sch B could improve cardiac function and attenuate myocardial remodeling after myocardial infarction (MI) in mice. Mice model of MI was established by permanent ligation of the left anterior descending (LAD) coronary artery. Then the MI mice were randomly treated with Sch B or vehicle alone. After treatment for 3 weeks, Sch B could increase survival rate, improve heart function and decrease infarct size compared with vehicle. Moreover, Sch B could down-regulate some inflammatory cytokines, activate eNOS pathway, inhibit cell apoptosis, and enhance cell proliferation. Further in vitro study on H9c2 cells showed similar effects of Sch B on prevention of hypoxia-induced inflammation and cell apoptosis. Taken together, our results demonstrate that Sch B can reduce inflammation, inhibit apoptosis, and improve cardiac function after ischemic injury. It represents a potential novel therapeutic approach for treatment of ischemic heart disease.

  18. Beneficial effects of schisandrin B on the cardiac function in mice model of myocardial infarction.

    Directory of Open Access Journals (Sweden)

    Pengsheng Chen

    Full Text Available The fruit of Schisandra chinensis has been used in the traditional Chinese medicine for thousands of years. Accumulating evidence suggests that Schisandrin B (Sch B has cardioprotection effect on myocardial ischemia in vitro. However, it is unclear whether Sch B has beneficial effects on continuous myocardial ischemia in vivo. The aim of the present study was to investigate whether Sch B could improve cardiac function and attenuate myocardial remodeling after myocardial infarction (MI in mice. Mice model of MI was established by permanent ligation of the left anterior descending (LAD coronary artery. Then the MI mice were randomly treated with Sch B or vehicle alone. After treatment for 3 weeks, Sch B could increase survival rate, improve heart function and decrease infarct size compared with vehicle. Moreover, Sch B could down-regulate some inflammatory cytokines, activate eNOS pathway, inhibit cell apoptosis, and enhance cell proliferation. Further in vitro study on H9c2 cells showed similar effects of Sch B on prevention of hypoxia-induced inflammation and cell apoptosis. Taken together, our results demonstrate that Sch B can reduce inflammation, inhibit apoptosis, and improve cardiac function after ischemic injury. It represents a potential novel therapeutic approach for treatment of ischemic heart disease.

  19. High-fat Diet Promotes Cardiac Remodeling in an Experimental Model of Obesity.

    Science.gov (United States)

    Martins, Fernando; Campos, Dijon Henrique Salomé; Pagan, Luana Urbano; Martinez, Paula Felippe; Okoshi, Katashi; Okoshi, Marina Politi; Padovani, Carlos Roberto; Souza, Albert Schiaveto de; Cicogna, Antonio Carlos; Oliveira-Junior, Silvio Assis de

    2015-11-01

    Although nutritional, metabolic and cardiovascular abnormalities are commonly seen in experimental studies of obesity, it is uncertain whether these effects result from the treatment or from body adiposity. To evaluate the influence of treatment and body composition on metabolic and cardiovascular aspects in rats receiving high saturated fat diet. Sixteen Wistar rats were used, distributed into two groups, the control (C) group, treated with isocaloric diet (2.93 kcal/g) and an obese (OB) group, treated with high-fat diet (3.64 kcal/g). The study period was 20 weeks. Analyses of nutritional behavior, body composition, glycemia, cholesterolemia, lipemia, systolic arterial pressure, echocardiography, and cardiac histology were performed. High-fat diet associates with manifestations of obesity, accompanied by changes in glycemia, cardiomyocyte hypertrophy, and myocardial interstitial fibrosis. After adjusting for adiposity, the metabolic effects were normalized, whereas differences in morphometric changes between groups were maintained. It was concluded that adiposity body composition has a stronger association with metabolic disturbances in obese rodents, whereas the high-fat dietary intervention is found to be more related to cardiac morphological changes in experimental models of diet-induced obesity.

  20. Three-dimensional modeling and quantitative analysis of gap junction distributions in cardiac tissue.

    Science.gov (United States)

    Lackey, Daniel P; Carruth, Eric D; Lasher, Richard A; Boenisch, Jan; Sachse, Frank B; Hitchcock, Robert W

    2011-11-01

    Gap junctions play a fundamental role in intercellular communication in cardiac tissue. Various types of heart disease including hypertrophy and ischemia are associated with alterations of the spatial arrangement of gap junctions. Previous studies applied two-dimensional optical and electron-microscopy to visualize gap junction arrangements. In normal cardiomyocytes, gap junctions were primarily found at cell ends, but can be found also in more central regions. In this study, we extended these approaches toward three-dimensional reconstruction of gap junction distributions based on high-resolution scanning confocal microscopy and image processing. We developed methods for quantitative characterization of gap junction distributions based on analysis of intensity profiles along the principal axes of myocytes. The analyses characterized gap junction polarization at cell ends and higher-order statistical image moments of intensity profiles. The methodology was tested in rat ventricular myocardium. Our analysis yielded novel quantitative data on gap junction distributions. In particular, the analysis demonstrated that the distributions exhibit significant variability with respect to polarization, skewness, and kurtosis. We suggest that this methodology provides a quantitative alternative to current approaches based on visual inspection, with applications in particular in characterization of engineered and diseased myocardium. Furthermore, we propose that these data provide improved input for computational modeling of cardiac conduction.

  1. Calcium Transients Closely Reflect Prolonged Action Potentials in iPSC Models of Inherited Cardiac Arrhythmia

    Directory of Open Access Journals (Sweden)

    C. Ian Spencer

    2014-08-01

    Full Text Available Long-QT syndrome mutations can cause syncope and sudden death by prolonging the cardiac action potential (AP. Ion channels affected by mutations are various, and the influences of cellular calcium cycling on LQTS cardiac events are unknown. To better understand LQTS arrhythmias, we performed current-clamp and intracellular calcium ([Ca2+]i measurements on cardiomyocytes differentiated from patient-derived induced pluripotent stem cells (iPS-CM. In myocytes carrying an LQT2 mutation (HERG-A422T, APs and [Ca2+]i transients were prolonged in parallel. APs were abbreviated by nifedipine exposure and further lengthened upon releasing intracellularly stored Ca2+. Validating this model, control iPS-CM treated with HERG-blocking drugs recapitulated the LQT2 phenotype. In LQT3 iPS-CM, expressing NaV1.5-N406K, APs and [Ca2+]i transients were markedly prolonged. AP prolongation was sensitive to tetrodotoxin and to inhibiting Na+-Ca2+ exchange. These results suggest that LQTS mutations act partly on cytosolic Ca2+ cycling, potentially providing a basis for functionally targeted interventions regardless of the specific mutation site.

  2. Cardiac hypertrophy is associated with altered thioredoxin and ASK-1 signaling in a mouse model of menopause.

    Science.gov (United States)

    Ebrahimian, Talin; Sairam, M Ram; Schiffrin, Ernesto L; Touyz, Rhian M

    2008-10-01

    Oxidative stress is implicated in menopause-associated hypertension and cardiovascular disease. The role of antioxidants in this process is unclear. We questioned whether the downregulation of thioredoxin (TRX) is associated with oxidative stress and the development of hypertension and target-organ damage (cardiac hypertrophy) in a menopause model. TRX is an endogenous antioxidant that also interacts with signaling molecules, such as apoptosis signal-regulated kinase 1 (ASK-1), independently of its antioxidant function. Aged female wild-type (WT) and follitropin receptor knockout (FORKO) mice (20-24 wk), with hormonal imbalances, were studied. Mice were infused with ANG II (400 ng x kg(-1) x min(-1); 14 days). Systolic blood pressure was increased by ANG II in WT (166+/-8 vs. 121+/-5 mmHg) and FORKO (176+/-7 vs. 115+/-5 mmHg; P<0.0001; n=9/group) mice. In ANG II-infused FORKO mice, cardiac mass was increased by 42% (P<0.001). This was associated with increased collagen content and augmented ERK1/2 phosphorylation (2-fold). Cardiac TRX expression and activity were decreased by ANG II in FORKO but not in WT (P<0.01) mice. ASK-1 expression, cleaved caspase III content, and Bax/Bcl-2 content were increased in ANG II-infused FORKO (P<0.05). ANG II had no effect on cardiac NAD(P)H oxidase activity or on O(2)(*-) levels in WT or FORKO. Cardiac ANG II type 1 receptor expression was similar in FORKO and WT. These findings indicate that in female FORKO, ANG II-induced cardiac hypertrophy and fibrosis are associated with the TRX downregulation and upregulation of ASK-1/caspase signaling. Our data suggest that in a model of menopause, protective actions of TRX may be blunted, which could contribute to cardiac remodeling independently of oxidative stress and hypertension.

  3. Ivabradine and metoprolol differentially affect cardiac glucose metabolism despite similar heart rate reduction in a mouse model of dyslipidemia.

    Science.gov (United States)

    Vaillant, Fanny; Lauzier, Benjamin; Ruiz, Matthieu; Shi, Yanfen; Lachance, Dominic; Rivard, Marie-Eve; Bolduc, Virginie; Thorin, Eric; Tardif, Jean-Claude; Des Rosiers, Christine

    2016-10-01

    While heart rate reduction (HRR) is a target for the management of patients with heart disease, contradictory results were reported using ivabradine, which selectively inhibits the pacemaker If current, vs. β-blockers like metoprolol. This study aimed at testing whether similar HRR with ivabradine vs. metoprolol differentially modulates cardiac energy substrate metabolism, a factor determinant for cardiac function, in a mouse model of dyslipidemia (hApoB(+/+);LDLR(-/-)). Following a longitudinal study design, we used 3- and 6-mo-old mice, untreated or treated for 3 mo with ivabradine or metoprolol. Cardiac function was evaluated in vivo and ex vivo in working hearts perfused with (13)C-labeled substrates to assess substrate fluxes through energy metabolic pathways. Compared with 3-mo-old, 6-mo-old dyslipidemic mice had similar cardiac hemodynamics in vivo but impaired (P ivabradine-treated hearts displayed significantly higher stroke volume values and glycolysis vs. their metoprolol-treated counterparts ex vivo, values for the ivabradine group being often not significantly different from 3-mo-old mice. Further analyses highlighted additional significant cardiac alterations with disease progression, namely in the total tissue level of proteins modified by O-linked N-acetylglucosamine (O-GlcNAc), whose formation is governed by glucose metabolism via the hexosamine biosynthetic pathway, which showed a similar pattern with ivabradine vs. metoprolol treatment. Collectively, our results emphasize the implication of alterations in cardiac glucose metabolism and signaling linked to disease progression in our mouse model. Despite similar HRR, ivabradine, but not metoprolol, preserved cardiac function and glucose metabolism during disease progression.

  4. Low-Cost Optical Mapping Systems for Panoramic Imaging of Complex Arrhythmias and Drug-Action in Translational Heart Models

    Science.gov (United States)

    Lee, Peter; Calvo, Conrado J.; Alfonso-Almazán, José M.; Quintanilla, Jorge G.; Chorro, Francisco J.; Yan, Ping; Loew, Leslie M.; Filgueiras-Rama, David; Millet, José

    2017-02-01

    Panoramic optical mapping is the primary method for imaging electrophysiological activity from the entire outer surface of Langendorff-perfused hearts. To date, it is the only method of simultaneously measuring multiple key electrophysiological parameters, such as transmembrane voltage and intracellular free calcium, at high spatial and temporal resolution. Despite the impact it has already had on the fields of cardiac arrhythmias and whole-heart computational modeling, present-day system designs precludes its adoption by the broader cardiovascular research community because of their high costs. Taking advantage of recent technological advances, we developed and validated low-cost optical mapping systems for panoramic imaging using Langendorff-perfused pig hearts, a clinically-relevant model in basic research and bioengineering. By significantly lowering financial thresholds, this powerful cardiac electrophysiology imaging modality may gain wider use in research and, even, teaching laboratories, which we substantiated using the lower-cost Langendorff-perfused rabbit heart model.

  5. Parameter sensitivity analysis of stochastic models provides insights into cardiac calcium sparks.

    Science.gov (United States)

    Lee, Young-Seon; Liu, Ona Z; Hwang, Hyun Seok; Knollmann, Bjorn C; Sobie, Eric A

    2013-03-05

    We present a parameter sensitivity analysis method that is appropriate for stochastic models, and we demonstrate how this analysis generates experimentally testable predictions about the factors that influence local Ca(2+) release in heart cells. The method involves randomly varying all parameters, running a single simulation with each set of parameters, running simulations with hundreds of model variants, then statistically relating the parameters to the simulation results using regression methods. We tested this method on a stochastic model, containing 18 parameters, of the cardiac Ca(2+) spark. Results show that multivariable linear regression can successfully relate parameters to continuous model outputs such as Ca(2+) spark amplitude and duration, and multivariable logistic regression can provide insight into how parameters affect Ca(2+) spark triggering (a probabilistic process that is all-or-none in a single simulation). Benchmark studies demonstrate that this method is less computationally intensive than standard methods by a factor of 16. Importantly, predictions were tested experimentally by measuring Ca(2+) sparks in mice with knockout of the sarcoplasmic reticulum protein triadin. These mice exhibit multiple changes in Ca(2+) release unit structures, and the regression model both accurately predicts changes in Ca(2+) spark amplitude (30% decrease in model, 29% decrease in experiments) and provides an intuitive and quantitative understanding of how much each alteration contributes to the result. This approach is therefore an effective, efficient, and predictive method for analyzing stochastic mathematical models to gain biological insight.

  6. SUMO-1 gene transfer improves cardiac function in a large-animal model of heart failure.

    Science.gov (United States)

    Tilemann, Lisa; Lee, Ahyoung; Ishikawa, Kiyotake; Aguero, Jaume; Rapti, Kleopatra; Santos-Gallego, Carlos; Kohlbrenner, Erik; Fish, Kenneth M; Kho, Changwon; Hajjar, Roger J

    2013-11-13

    Recently, the impact of small ubiquitin-related modifier 1 (SUMO-1) on the regulation and preservation of sarcoplasmic reticulum calcium adenosine triphosphatase (SERCA2a) function was discovered. The amount of myocardial SUMO-1 is decreased in failing hearts, and its knockdown results in severe heart failure (HF) in mice. In a previous study, we showed that SUMO-1 gene transfer substantially improved cardiac function in a murine model of pressure overload-induced HF. Toward clinical translation, we evaluated in this study the effects of SUMO-1 gene transfer in a swine model of ischemic HF. One month after balloon occlusion of the proximal left anterior descending artery followed by reperfusion, the animals were randomized to receive either SUMO-1 at two doses, SERCA2a, or both by adeno-associated vector type 1 (AAV1) gene transfer via antegrade coronary infusion. Control animals received saline infusions. After gene delivery, there was a significant increase in the maximum rate of pressure rise [dP/dt(max)] that was most pronounced in the group that received both SUMO-1 and SERCA2a. The left ventricular ejection fraction (LVEF) improved after high-dose SUMO-1 with or without SERCA2a gene delivery, whereas there was a decline in LVEF in the animals receiving saline. Furthermore, the dilatation of LV volumes was prevented in the treatment groups. SUMO-1 gene transfer therefore improved cardiac function and stabilized LV volumes in a large-animal model of HF. These results support the critical role of SUMO-1 in SERCA2a function and underline the therapeutic potential of SUMO-1 for HF patients.

  7. Error and reinforcement processing in ADHD : An electrophysiological study

    NARCIS (Netherlands)

    Groen, Yvonne

    2011-01-01

    Introduction and Objective(s) Current explanatory models of ADHD suggest abnormal reinforcement sensitivity, but the exact nature of this deficit is unclear. In this study we investigate electrophysiological reactions to positive/negative reinforcement as well as correct/error responses to gain more

  8. Effect of heart rate on CT angiography using the enhanced cardiac model of the 4D NCAT

    Science.gov (United States)

    Segars, W. P.; Taguchi, K.; Fung, G. S. K.; Fishman, E. K.; Tsui, B. M. W.

    2006-03-01

    We investigate the effect of heart rate on the quality and artifact generation in coronary artery images obtained using multi-slice computed tomography (MSCT) with the purpose of finding the optimal time resolution for data acquisition. To perform the study, we used the 4D NCAT phantom, a computer model of the normal human anatomy and cardiac and respiratory motions developed in our laboratory. Although capable of being far more realistic, the 4D NCAT cardiac model was originally designed for low-resolution imaging research, and lacked the anatomical detail to be applicable to high-resolution CT. In this work, we updated the cardiac model to include a more detailed anatomy and physiology based on high-resolution clinical gated MSCT data. To demonstrate its utility in high-resolution dynamic CT imaging research, the enhanced 4D NCAT was then used in a pilot simulation study to investigate the effect of heart rate on CT angiography. The 4D NCAT was used to simulate patients with different heart rates (60-120 beats/minute) and with various cardiac plaques of known size and location within the coronary arteries. For each simulated patient, MSCT projection data was generated with data acquisition windows ranging from 100 to 250 ms centered within the quiet phase (mid-diastole) of the heart using an analytical CT projection algorithm. CT images were reconstructed from the projection data, and the contrast of the plaques was then measured to assess the effect of heart rate and to determine the optimal time resolution required for each case. The 4D NCAT phantom with its realistic model for the cardiac motion was found to provide a valuable tool from which to optimize CT cardiac applications. Our results indicate the importance of optimizing the time resolution with regard to heart rate and plaque location for improved CT images at a reduced patient dose.

  9. Performance of hybrid programming models for multiscale cardiac simulations: preparing for petascale computation.

    Science.gov (United States)

    Pope, Bernard J; Fitch, Blake G; Pitman, Michael C; Rice, John J; Reumann, Matthias

    2011-10-01

    Future multiscale and multiphysics models that support research into human disease, translational medical science, and treatment can utilize the power of high-performance computing (HPC) systems. We anticipate that computationally efficient multiscale models will require the use of sophisticated hybrid programming models, mixing distributed message-passing processes [e.g., the message-passing interface (MPI)] with multithreading (e.g., OpenMP, Pthreads). The objective of this study is to compare the performance of such hybrid programming models when applied to the simulation of a realistic physiological multiscale model of the heart. Our results show that the hybrid models perform favorably when compared to an implementation using only the MPI and, furthermore, that OpenMP in combination with the MPI provides a satisfactory compromise between performance and code complexity. Having the ability to use threads within MPI processes enables the sophisticated use of all processor cores for both computation and communication phases. Considering that HPC systems in 2012 will have two orders of magnitude more cores than what was used in this study, we believe that faster than real-time multiscale cardiac simulations can be achieved on these systems.

  10. Regional assessment of LV wall in infarcted heart using tagged MRI and cardiac modelling

    Science.gov (United States)

    Jahanzad, Zeinab; Miin Liew, Yih; Bilgen, Mehmet; McLaughlin, Robert A.; Onn Leong, Chen; Chee, Kok Han; Aziz, Yang Faridah Abdul; Ung, Ngie Min; Lai, Khin Wee; Ng, Siew-Cheok; Lim, Einly

    2015-05-01

    A segmental two-parameter empirical deformable model is proposed for evaluating regional motion abnormality of the left ventricle. Short-axis tagged MRI scans were acquired from 10 healthy subjects and 10 postinfarct patients. Two motion parameters, contraction and rotation, were quantified for each cardiac segment by fitting the proposed model using a non-rigid registration algorithm. The accuracy in motion estimation was compared to a global model approach. Motion parameters extracted from patients were correlated to infarct transmurality assessed with delayed-contrast-enhanced MRI. The proposed segmental model allows markedly improved accuracy in regional motion analysis as compared to the global model for both subject groups (1.22-1.40 mm versus 2.31-2.55 mm error). By end-systole, all healthy segments experienced radial displacement by ~25-35% of the epicardial radius, whereas the 3 short-axis planes rotated differently (basal: 3.3° mid:  -1° and apical:  -4.6°) to create a twisting motion. While systolic contraction showed clear correspondence to infarct transmurality, rotation was nonspecific to either infarct location or transmurality but could indicate the presence of functional abnormality. Regional contraction and rotation derived using this model could potentially aid in the assessment of severity of regional dysfunction of infarcted myocardium.

  11. Aortocaval Fistula in Rat: A Unique Model of Volume-Overload Congestive Heart Failure and Cardiac Hypertrophy

    Directory of Open Access Journals (Sweden)

    Zaid Abassi

    2011-01-01

    Full Text Available Despite continuous progress in our understanding of the pathogenesis of congestive heart failure (CHF and its management, mortality remains high. Therefore, development of reliable experimental models of CHF and cardiac hypertrophy is essential to better understand disease progression and allow new therapy developement. The aortocaval fistula (ACF model, first described in dogs almost a century ago, has been adopted in rodents by several groups including ours. Although considered to be a model of high-output heart failure, its long-term renal and cardiac manifestations are similar to those seen in patients with low-output CHF. These include Na+-retention, cardiac hypertrophy and increased activity of both vasoconstrictor/antinatriureticneurohormonal systems and compensatory vasodilating/natriuretic systems. Previous data from our group and others suggest that progression of cardiorenal pathophysiology in this model is largely determined by balance between opposing hormonal forces, as reflected in states of CHF decompensation that are characterized by overactivation of vasoconstrictive/Na+-retaining systems. Thus, ACF serves as a simple, cheap, and reproducible platform to investigate the pathogenesis of CHF and to examine efficacy of new therapeutic approaches. Hereby, we will focus on the neurohormonal, renal, and cardiac manifestations of the ACF model in rats, with special emphasis on our own experience.

  12. Comparison of Cerebral Metabolism between Pig Ventricular Fibrillation and Asphyxial Cardiac Arrest Models

    Institute of Scientific and Technical Information of China (English)

    Yi Zhang; Chun-Sheng Li; Cai-Jun Wu; Jun Yang; Chen-Chen Hang

    2015-01-01

    Background:Morbidity and mortality after resuscitation largely depend on the recovery of brain function.Ventricular fibrillation cardiac arrest (VFCA) and asphyxial cardiac arrest (ACA) are the two most prevalent causes of sudden cardiac death.Up to now,most studies have focused on VFCA.However,results from the two models have been largely variable.So,it is necessary to characterize the features of postresuscitation cerebral metabolism of both models.Methods:Forty-four Wuzhishan miniature inbred pigs were randomly divided into three groups:18 for VFCA group,ACA group,respectively,and other 8 for sham-operated group (SHAM).VFCA was induced by programmed electric stimulation,andACA was induced by endotracheal tube clamping.After 8 min without treatment,standard cardiopulmonary resuscitation (CPR) was initiated.Following neurological deficit scores (NDS) were evaluated at 24 h after achievement of spontaneous circulation,cerebral metabolism showed as the maximum standardized uptake value (SUVmax) was measured by 18F-fluorodeoxyglucose positron emission tomography/computed tomography.Levels of serum markers of brain injury,neuron specific enolase (NSE),and S100β were quantified with an enzyme-linked immunosorbent assay.Results:Compared with VFCA group,fewer ACA animals achieved restoration of spontaneous circulation (61.1% vs.94.4%,P < 0.01) and survived 24-h after resuscitation (38.9% vs.77.8%,P < 0.01) with worse neurological outcome (NDS:244.3 ± 15.3 vs.168.8 ± 9.71,P < 0.01).The CPR duration of ACA group was longer than that of VFCA group (8.1 ± 1.2 min vs.4.5 ± 1.1 min,P < 0.01).Cerebral energy metabolism showed as SUVmax in ACA was lower than in VFCA (P < 0.05 or P < 0.01).Higher serum biomarkers of brain damage (NSE,S100β) were found inACA than VFCA after resuscitation (P < 0.01).Conclusions:Compared with VFCA,ACA causes more severe cerebral metabolism injuries with less successful resuscitation and worse neurological outcome.

  13. Comparison of Cerebral Metabolism between Pig Ventricular Fibrillation and Asphyxial Cardiac Arrest Models

    Directory of Open Access Journals (Sweden)

    Yi Zhang

    2015-01-01

    Full Text Available Background: Morbidity and mortality after resuscitation largely depend on the recovery of brain function. Ventricular fibrillation cardiac arrest (VFCA and asphyxial cardiac arrest (ACA are the two most prevalent causes of sudden cardiac death. Up to now, most studies have focused on VFCA. However, results from the two models have been largely variable. So, it is necessary to characterize the features of postresuscitation cerebral metabolism of both models. Methods: Forty-four Wuzhishan miniature inbred pigs were randomly divided into three groups: 18 for VFCA group, ACA group, respectively, and other 8 for sham-operated group (SHAM. VFCA was induced by programmed electric stimulation, and ACA was induced by endotracheal tube clamping. After 8 min without treatment, standard cardiopulmonary resuscitation (CPR was initiated. Following neurological deficit scores (NDS were evaluated at 24 h after achievement of spontaneous circulation, cerebral metabolism showed as the maximum standardized uptake value (SUVmax was measured by 18 F-fluorodeoxyglucose positron emission tomography/computed tomography. Levels of serum markers of brain injury, neuron specific enolase (NSE, and S100β were quantified with an enzyme-linked immunosorbent assay. Results: Compared with VFCA group, fewer ACA animals achieved restoration of spontaneous circulation (61.1% vs. 94.4%, P < 0.01 and survived 24-h after resuscitation (38.9% vs. 77.8%, P < 0.01 with worse neurological outcome (NDS: 244.3 ± 15.3 vs. 168.8 ± 9.71, P < 0.01. The CPR duration of ACA group was longer than that of VFCA group (8.1 ± 1.2 min vs. 4.5 ± 1.1 min, P < 0.01. Cerebral energy metabolism showed as SUVmax in ACA was lower than in VFCA (P < 0.05 or P < 0.01. Higher serum biomarkers of brain damage (NSE, S100β were found in ACA than VFCA after resuscitation (P < 0.01. Conclusions: Compared with VFCA, ACA causes more severe cerebral metabolism injuries with less successful resuscitation and worse

  14. Cardiac catheterization and angiography, 3d Ed

    Energy Technology Data Exchange (ETDEWEB)

    Grossman, W.

    1986-01-01

    This textbook was first published in 1974 and subsequently revised in 1980. The current edition, in seven parts and 33 chapters, has been extensively rewritten, and new chapters have been added that present recently developed techniques. The references have been updated to 1985. The purpose of this work is to provide a concise description of the major techniques employed in cardiac catheterization and angiography. Part 1 deals with the history, general principles, and practice of cardiac catheterization and angiography. In part 2, various techniques of cardiac catheterization are discussed and compared. In part 3, techniques for the determination of cardiac output, pressure, resistance, valve area, and shunt flow are described. Part 4 deals briefly with coronary angiography, cardiac ventriculography, pulmonary angiography, and aortography. In part 5, techniques for evaluating cardiac function and intracardiac electrophysiology are presented. The characteristic hemodynamic and angiographic abnormalities in specific disorders are described in part 6. Part 7 deals with special catheter techniques.

  15. Computational modeling of voltage-gated Ca channels inhibition: identification of different effects on uterine and cardiac action potentials

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    Wing Chiu eTong

    2014-10-01

    Full Text Available The uterus and heart share the important physiological feature whereby contractile activation of the muscle tissue is regulated by the generation of periodic, spontaneous electrical action potentials (APs. Preterm birth arising from premature uterine contractions is a major complication of pregnancy and there remains a need to pursue avenues of research that facilitate the use of drugs, tocolytics, to limit these inappropriate contractions without deleterious actions on cardiac electrical excitation. A novel approach is to make use of mathematical models of uterine and cardiac APs, which incorporate many ionic currents contributing to the AP forms, and test the cell-specific responses to interventions. We have used three such models – of uterine smooth muscle cells (USMC, cardiac sinoatrial node cells (SAN and ventricular cells – to investigate the relative effects of reducing two important voltage-gated Ca currents – the L-type (ICaL and T-type (ICaT Ca currents. Reduction of ICaL (10% alone, or ICaT (40% alone, blunted USMC APs with little effect on ventricular APs and only mild effects on SAN activity. Larger reductions in either current further attenuated the USMC APs but with also greater effects on SAN APs. Encouragingly, a combination of ICaL and ICaT reduction did blunt USMC APs as intended with little detriment to APs of either cardiac cell type. Subsequent overlapping maps of ICaL and ICaT inhibition profiles from each model revealed a range of combined reductions of ICaL and ICaT over which an appreciable diminution of USMC APs could be achieved with no deleterious action on cardiac SAN or ventricular APs. This novel approach illustrates the potential for computational biology to inform us of possible uterine and cardiac cell-specific mechanisms. Incorporating such computational approaches in future studies directed at designing new, or repurposing existing, tocolytics will be beneficial for establishing a desired uterine

  16. Cholinergic Signaling Exerts Protective Effects in Models of Sympathetic Hyperactivity-Induced Cardiac Dysfunction

    Science.gov (United States)

    Gavioli, Mariana; Lara, Aline; Almeida, Pedro W. M.; Lima, Augusto Martins; Damasceno, Denis D.; Rocha-Resende, Cibele; Ladeira, Marina; Resende, Rodrigo R.; Martinelli, Patricia M.; Melo, Marcos Barrouin; Brum, Patricia C.; Fontes, Marco Antonio Peliky; Souza Santos, Robson A.; Prado, Marco A. M.; Guatimosim, Silvia

    2014-01-01

    Cholinergic control of the heart is exerted by two distinct branches; the autonomic component represented by the parasympathetic nervous system, and the recently described non-neuronal cardiomyocyte cholinergic machinery. Previous evidence has shown that reduced cholinergic function leads to deleterious effects on the myocardium. Yet, whether conditions of increased cholinergic signaling can offset the pathological remodeling induced by sympathetic hyperactivity, and its consequences for these two cholinergic axes are unknown. Here, we investigated two models of sympathetic hyperactivity: i) the chronic beta-adrenergic receptor stimulation evoked by isoproterenol (ISO), and ii) the α2A/α2C-adrenergic receptor knockout (KO) mice that lack pre-synaptic adrenergic receptors. In both models, cholinergic signaling was increased by administration of the cholinesterase inhibitor, pyridostigmine. First, we observed that isoproterenol produces an autonomic imbalance characterized by increased sympathetic and reduced parasympathetic tone. Under this condition transcripts for cholinergic proteins were upregulated in ventricular myocytes, indicating that non-neuronal cholinergic machinery is activated during adrenergic overdrive. Pyridostigmine treatment prevented the effects of ISO on autonomic function and on the ventricular cholinergic machinery, and inhibited cardiac remodeling. α2A/α2C-KO mice presented reduced ventricular contraction when compared to wild-type mice, and this dysfunction was also reversed by cholinesterase inhibition. Thus, the cardiac parasympathetic system and non-neuronal cardiomyocyte cholinergic machinery are modulated in opposite directions under conditions of increased sympathetic drive or ACh availability. Moreover, our data support the idea that pyridostigmine by restoring ACh availability is beneficial in heart disease. PMID:24992197

  17. Cholinergic signaling exerts protective effects in models of sympathetic hyperactivity-induced cardiac dysfunction.

    Directory of Open Access Journals (Sweden)

    Mariana Gavioli

    Full Text Available Cholinergic control of the heart is exerted by two distinct branches; the autonomic component represented by the parasympathetic nervous system, and the recently described non-neuronal cardiomyocyte cholinergic machinery. Previous evidence has shown that reduced cholinergic function leads to deleterious effects on the myocardium. Yet, whether conditions of increased cholinergic signaling can offset the pathological remodeling induced by sympathetic hyperactivity, and its consequences for these two cholinergic axes are unknown. Here, we investigated two models of sympathetic hyperactivity: i the chronic beta-adrenergic receptor stimulation evoked by isoproterenol (ISO, and ii the α2A/α2C-adrenergic receptor knockout (KO mice that lack pre-synaptic adrenergic receptors. In both models, cholinergic signaling was increased by administration of the cholinesterase inhibitor, pyridostigmine. First, we observed that isoproterenol produces an autonomic imbalance characterized by increased sympathetic and reduced parasympathetic tone. Under this condition transcripts for cholinergic proteins were upregulated in ventricular myocytes, indicating that non-neuronal cholinergic machinery is activated during adrenergic overdrive. Pyridostigmine treatment prevented the effects of ISO on autonomic function and on the ventricular cholinergic machinery, and inhibited cardiac remodeling. α2A/α2C-KO mice presented reduced ventricular contraction when compared to wild-type mice, and this dysfunction was also reversed by cholinesterase inhibition. Thus, the cardiac parasympathetic system and non-neuronal cardiomyocyte cholinergic machinery are modulated in opposite directions under conditions of increased sympathetic drive or ACh availability. Moreover, our data support the idea that pyridostigmine by restoring ACh availability is beneficial in heart disease.

  18. Diclofenac plasma protein binding: PK-PD modelling in cardiac patients submitted to cardiopulmonary bypass

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    Auler Jr. J.O.

    1997-01-01

    Full Text Available Twenty-four surgical patients of both sexes without cardiac, hepatic, renal or endocrine dysfunctions were divided into two groups: 10 cardiac surgical patients submitted to myocardial revascularization and cardiopulmonary bypass (CPB, 3 females and 7 males aged 65 ± 11 years, 74 ± 16 kg body weight, 166 ± 9 cm height and 1.80 ± 0.21 m2 body surface area (BSA, and control, 14 surgical patients not submitted to CPB, 11 female and 3 males aged 41 ± 14 years, 66 ± 14 kg body weight, 159 ± 9 cm height and 1.65 ± 0.16 m2 BSA (mean ± SD. Sodium diclofenac (1 mg/kg, im Voltaren 75® twice a day was administered to patients in the Recovery Unit 48 h after surgery. Venous blood samples were collected during a period of 0-12 h and analgesia was measured by the visual analogue scale (VAS during the same period. Plasma diclofenac levels were measured by high performance liquid chromatography. A two-compartment open model was applied to obtain the plasma decay curve and to estimate kinetic parameters. Plasma diclofenac protein binding decreased whereas free plasma diclofenac levels were increased five-fold in CPB patients. Data obtained for analgesia reported as the maximum effect (EMAX were: 25% VAS (CPB vs 10% VAS (control, P<0.05, median measured by the visual analogue scale where 100% is equivalent to the highest level of pain. To correlate the effect versus plasma diclofenac levels, the EMAX sigmoid model was applied. A prolongation of the mean residence time for maximum effect (MRTEMAX was observed without any change in lag-time in CPB in spite of the reduced analgesia reported for these patients, during the time-dose interval. In conclusion, the extent of plasma diclofenac protein binding was influenced by CPB with clinically relevant kinetic-dynamic consequences

  19. Regulation of excitation-contraction coupling in mouse cardiac myocytes: integrative analysis with mathematical modelling

    Directory of Open Access Journals (Sweden)

    Weckström Matti

    2009-08-01

    normal and defective cellular physiology. We propose that integrative modelling as in the present work is a valuable complement to experiments in understanding the causality within complex biological systems such as cardiac myocytes.

  20. Abnormal sodium current properties contribute to cardiac electrical and contractile dysfunction in a mouse model of myotonic dystrophy type 1.

    Science.gov (United States)

    Algalarrondo, Vincent; Wahbi, Karim; Sebag, Frédéric; Gourdon, Geneviève; Beldjord, Chérif; Azibi, Kamel; Balse, Elise; Coulombe, Alain; Fischmeister, Rodolphe; Eymard, Bruno; Duboc, Denis; Hatem, Stéphane N

    2015-04-01

    Myotonic dystrophy type 1 (DM1) is the most common neuromuscular disorder and is associated with cardiac conduction defects. However, the mechanisms of cardiac arrhythmias in DM1 are unknown. We tested the hypothesis that abnormalities in the cardiac sodium current (INa) are involved, and used a transgenic mouse model reproducing the expression of triplet expansion observed in DM1 (DMSXL mouse). The injection of the class-I antiarrhythmic agent flecainide induced prominent conduction abnormalities and significantly lowered the radial tissular velocities and strain rate in DMSXL mice compared to WT. These abnormalities were more pronounced in 8-month-old mice than in 3-month-old mice. Ventricular action potentials recorded by standard glass microelectrode technique exhibited a lower maximum upstroke velocity [dV/dt](max) in DMSXL. This decreased [dV/dt](max) was associated with a 1.7 fold faster inactivation of INa in DMSXL myocytes measured by the whole-cell patch-clamp technique. Finally in the DMSXL mouse, no mutation in the Scn5a gene was detected and neither cardiac fibrosis nor abnormalities of expression of the sodium channel protein were observed. Therefore, alterations in the sodium current markedly contributed to electrical conduction block in DM1. This result should guide pharmaceutical and clinical research toward better therapy for the cardiac arrhythmias associated with DM1.

  1. 3-OST-7 regulates BMP-dependent cardiac contraction.

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    Shiela C Samson

    2013-12-01

    Full Text Available The 3-O-sulfotransferase (3-OST family catalyzes rare modifications of glycosaminoglycan chains on heparan sulfate proteoglycans, yet their biological functions are largely unknown. Knockdown of 3-OST-7 in zebrafish uncouples cardiac ventricular contraction from normal calcium cycling and electrophysiology by reducing tropomyosin4 (tpm4 expression. Normal 3-OST-7 activity prevents the expansion of BMP signaling into ventricular myocytes, and ectopic activation of BMP mimics the ventricular noncontraction phenotype seen in 3-OST-7 depleted embryos. In 3-OST-7 morphants, ventricular contraction can be rescued by overexpression of tropomyosin tpm4 but not by troponin tnnt2, indicating that tpm4 serves as a lynchpin for ventricular sarcomere organization downstream of 3-OST-7. Contraction can be rescued by expression of 3-OST-7 in endocardium, or by genetic loss of bmp4. Strikingly, BMP misregulation seen in 3-OST-7 morphants also occurs in multiple cardiac noncontraction models, including potassium voltage-gated channel gene, kcnh2, affected in Romano-Ward syndrome and long-QT syndrome, and cardiac troponin T gene, tnnt2, affected in human cardiomyopathies. Together these results reveal 3-OST-7 as a key component of a novel pathway that constrains BMP signaling from ventricular myocytes, coordinates sarcomere assembly, and promotes cardiac contractile function.

  2. From teeth, skin, blood to heart : induced pluripotent stem cells as an in vitro model for cardiac disease

    NARCIS (Netherlands)

    Dambrot, Cheryl Susan

    2014-01-01

    Since the first reports of human induced pluripotent stem cells (hiPSC), the field of pluripotent stem cell (PSC) research has grown in leap and bounds, particularly in the area of (cardiac) disease modeling. This is in part because it is fairly easy to produce cardiomyocytes from hPSC and also ther

  3. Ion Channel ElectroPhysiology Ontology (ICEPO) - a case study of text mining assisted ontology development.

    Science.gov (United States)

    Elayavilli, Ravikumar Komandur; Liu, Hongfang

    2016-01-01

    Computational modeling of biological cascades is of great interest to quantitative biologists. Biomedical text has been a rich source for quantitative information. Gathering quantitative parameters and values from biomedical text is one significant challenge in the early steps of computational modeling as it involves huge manual effort. While automatically extracting such quantitative information from bio-medical text may offer some relief, lack of ontological representation for a subdomain serves as impedance in normalizing textual extractions to a standard representation. This may render textual extractions less meaningful to the domain experts. In this work, we propose a rule-based approach to automatically extract relations involving quantitative data from biomedical text describing ion channel electrophysiology. We further translated the quantitative assertions extracted through text mining to a formal representation that may help in constructing ontology for ion channel events using a rule based approach. We have developed Ion Channel ElectroPhysiology Ontology (ICEPO) by integrating the information represented in closely related ontologies such as, Cell Physiology Ontology (CPO), and Cardiac Electro Physiology Ontology (CPEO) and the knowledge provided by domain experts. The rule-based system achieved an overall F-measure of 68.93% in extracting the quantitative data assertions system on an independently annotated blind data set. We further made an initial attempt in formalizing the quantitative data assertions extracted from the biomedical text into a formal representation that offers potential to facilitate the integration of text mining into ontological workflow, a novel aspect of this study. This work is a case study where we created a platform that provides formal interaction between ontology development and text mining. We have achieved partial success in extracting quantitative assertions from the biomedical text and formalizing them in ontological

  4. Hepato-cardiac disorders

    Institute of Scientific and Technical Information of China (English)

    Yasser; Mahrous; Fouad; Reem; Yehia

    2014-01-01

    Understanding the mutual relationship between the liver and the heart is important for both hepatologists and cardiologists. Hepato-cardiac diseases can be classified into heart diseases affecting the liver, liver diseases affecting the heart, and conditions affecting the heart and the liver at the same time. Differential diagnoses of liver injury are extremely important in a cardiologist’s clinical practice calling for collaboration between cardiologists and hepatologists due to the many other diseases that can affect the liver and mimic haemodynamic injury. Acute and chronic heart failure may lead to acute ischemic hepatitis or chronic congestive hepatopathy. Treatment in these cases should be directed to the primary heart disease. In patients with advanced liver disease, cirrhotic cardiomyopathy may develop including hemodynamic changes, diastolic and systolic dysfunctions, reduced cardiac performance and electrophysiological abnormalities. Cardiac evaluation is important for patients with liver diseases especially before and after liver transplantation. Liver transplantation may lead to the improvement of all cardiac changes and the reversal of cirrhotic cardiomyopathy. There are systemic diseases that may affect both the liver and the heart concomitantly including congenital, metabolic and inflammatory diseases as well as alcoholism. This review highlights these hepatocardiac diseases

  5. Modeling the response of normal and ischemic cardiac tissue to electrical stimulation

    Science.gov (United States)

    Kandel, Sunil Mani

    Heart disease, the leading cause of death worldwide, is often caused by ventricular fibrillation. A common treatment for this lethal arrhythmia is defibrillation: a strong electrical shock that resets the heart to its normal rhythm. To design better defibrillators, we need a better understanding of both fibrillation and defibrillation. Fundamental mysteries remain regarding the mechanism of how the heart responds to a shock, particularly anodal shocks and the resultant hyperpolarization. Virtual anodes play critical roles in defibrillation, and one cannot build better defibrillators until these mechanisms are understood. We are using mathematical modeling to numerically simulate observed phenomena, and are exploring fundamental mechanisms responsible for the heart's electrical behavior. Such simulations clarify mechanisms and identify key parameters. We investigate how systolic tissue responds to an anodal shock and how refractory tissue reacts to hyperpolarization by studying the dip in the anodal strength-interval curve. This dip is due to electrotonic interaction between regions of depolarization and hyperpolarization following a shock. The dominance of the electrotonic mechanism over calcium interactions implies the importance of the spatial distribution of virtual electrodes. We also investigate the response of localized ischemic tissue to an anodal shock by modeling a regional elevation of extracellular potassium concentration. This heterogeneity leads to action potential instability, 2:1 conduction block (alternans), and reflection-like reentry at the boarder of the normal and ischemic regions. This kind of reflection (reentry) occurs due to the delay between proximal and distal segments to re-excite the proximal segment. Our numerical simulations are based on the bidomain model, the state-of-the-art mathematical description of how cardiac tissue responds to shocks. The dynamic LuoRudy model describes the active properties of the membrane. To model ischemia

  6. Modeling cardiac β-adrenergic signaling with normalized-Hill differential equations: comparison with a biochemical model

    Directory of Open Access Journals (Sweden)

    Saucerman Jeffrey J

    2010-11-01

    Full Text Available Abstract Background New approaches are needed for large-scale predictive modeling of cellular signaling networks. While mass action and enzyme kinetic approaches require extensive biochemical data, current logic-based approaches are used primarily for qualitative predictions and have lacked direct quantitative comparison with biochemical models. Results We developed a logic-based differential equation modeling approach for cell signaling networks based on normalized Hill activation/inhibition functions controlled by logical AND and OR operators to characterize signaling crosstalk. Using this approach, we modeled the cardiac β1-adrenergic signaling network, including 36 reactions and 25 species. Direct comparison of this model to an extensively characterized and validated biochemical model of the same network revealed that the new model gave reasonably accurate predictions of key network properties, even with default parameters. Normalized Hill functions improved quantitative predictions of global functional relationships compared with prior logic-based approaches. Comprehensive sensitivity analysis revealed the significant role of PKA negative feedback on upstream signaling and the importance of phosphodiesterases as key negative regulators of the network. The model was then extended to incorporate recently identified protein interaction data involving integrin-mediated mechanotransduction. Conclusions The normalized-Hill differential equation modeling approach allows quantitative prediction of network functional relationships and dynamics, even in systems with limited biochemical data.

  7. Evaluation of coronary blood flow velocity during cardiac arrest with circulation maintained through mechanical chest compressions in a porcine model

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    Wagner Henrik

    2011-12-01

    Full Text Available Abstract Background Mechanical chest compressions (CCs have been shown capable of maintaining circulation in humans suffering cardiac arrest for extensive periods of time. Reports have documented a visually normalized coronary blood flow during angiography in such cases (TIMI III flow, but it has never been actually measured. Only indirect measurements of the coronary circulation during cardiac arrest with on-going mechanical CCs have been performed previously through measurement of the coronary perfusion pressure (CPP. In this study our aim was to correlate average peak coronary flow velocity (APV to CPP during mechanical CCs. Methods In a closed chest porcine model, cardiac arrest was established through electrically induced ventricular fibrillation (VF in eleven pigs. After one minute, mechanical chest compressions were initiated and then maintained for 10 minutes upon which the pigs were defibrillated. Measurements of coronary blood flow in the left anterior descending artery were made at baseline and during VF with a catheter based Doppler flow fire measuring APV. Furthermore measurements of central (thoracic venous and arterial pressures were also made in order to calculate the theoretical CPP. Results Average peak coronary flow velocity was significantly higher compared to baseline during mechanical chests compressions and this was observed during the entire period of mechanical chest compressions (12 - 39% above baseline. The APV slowly declined during the 10 min period of mechanical chest compressions, but was still higher than baseline at the end of mechanical chest compressions. CPP was simultaneously maintained at > 20 mmHg during the 10 minute episode of cardiac arrest. Conclusion Our study showed good correlation between CPP and APV which was highly significant, during cardiac arrest with on-going mechanical CCs in a closed chest porcine model. In addition APV was even higher during mechanical CCs compared to baseline. Mechanical

  8. Human Mesenchymal Stromal Cells Improve Cardiac Perfusion in an Ovine Immunocompetent Animal Model.

    Science.gov (United States)

    Dayan, Victor; Sotelo, Veronica; Delfina, Valentina; Delgado, Natalia; Rodriguez, Carlos; Suanes, Carol; Langhain, María; Ferrando, Rodolfo; Keating, Armand; Benech, Alejandro; Touriño, Cristina

    2016-08-01

    Mesenchymal stromal cells (MSCs) hold considerable promise in the treatment of ischemic heart disease. Most preclinical studies of MSCs for acute myocardial infarction (AMI) have been performed either in syngeneic animal models or with human cells in xenogeneic immunodeficient animals. A preferable pre-clinical model, however, would involve human MSCs in an immunocompetent animal. AMI was generated in adult sheep by inducing ischemia reperfusion of the second diagonal branch. Sheep (n = 10) were randomized to receive an intravenous injection of human MSCs (1 × 10(6) cells/kg) or phosphate buffered saline. Cardiac function and remodeling were evaluated with echocardiography. Perfusion scintigraphy was used to identify sustained myocardial ischemia. Interaction between human MSCs and ovine lymphocytes was assessed by a mixed lymphocyte response (MLR). Sheep receiving human MSCs showed significant improvement in myocardial perfusion at 1 month compared with baseline measurements. There was no change in ventricular dimensions in either group after 1 month of AMI. No adverse events or symptoms were observed in the sheep receiving human MSCs. The MLR was negative. The immunocompetent ovine AMI model demonstrates the clinical safety and efficacy of human MSCs. The human cells do not appear to be immunogenic, further suggesting that immunocompetent sheep may serve as a suitable pre-clinical large animal model for testing human MSCs.

  9. Personalised computational cardiology: Patient-specific modelling in cardiac mechanics and biomaterial injection therapies for myocardial infarction

    Science.gov (United States)

    Sack, Kevin L.; Davies, Neil H.; Guccione, Julius M.

    2016-01-01

    Predictive computational modelling in biomedical research offers the potential to integrate diverse data, uncover biological mechanisms that are not easily accessible through experimental methods and expose gaps in knowledge requiring further research. Recent developments in computing and diagnostic technologies have initiated the advancement of computational models in terms of complexity and specificity. Consequently, computational modelling can increasingly be utilised as enabling and complementing modality in the clinic—with medical decisions and interventions being personalised. Myocardial infarction and heart failure are amongst the leading causes of death globally despite optimal modern treatment. The development of novel MI therapies is challenging and may be greatly facilitated through predictive modelling. Here, we review the advances in patient-specific modelling of cardiac mechanics, distinguishing specificity in cardiac geometry, myofibre architecture and mechanical tissue properties. Thereafter, the focus narrows to the mechanics of the infarcted heart and treatment of myocardial infarction with particular attention on intramyocardial biomaterial delivery. PMID:26833320

  10. miR-1 exacerbates cardiac ischemia-reperfusion injury in mouse models.

    Directory of Open Access Journals (Sweden)

    Zhenwei Pan

    Full Text Available Recent studies have revealed the critical role of microRNAs (miRNAs in regulating cardiac injury. Among them, the cardiac enriched microRNA-1(miR-1 has been extensively investigated and proven to be detrimental to cardiac myocytes. However, solid in vivo evidence for the role of miR-1 in cardiac injury is still missing and the potential therapeutic advantages of systemic knockdown of miR-1 expression remained unexplored. In this study, miR-1 transgenic (miR-1 Tg mice and locked nucleic acid modified oligonucleotide against miR-1 (LNA-antimiR-1 were used to explore the effects of miR-1 on cardiac ischemia/reperfusion injury (30 min ischemia followed by 24 h reperfusion. The cardiac miR-1 level was significantly increased in miR-1 Tg mice, and suppressed in LNA-antimiR-1 treated mice. When subjected to ischemia/reperfusion injury, miR-1 overexpression exacerbated cardiac injury, manifested by increased LDH, CK levels, caspase-3 expression, apoptosis and cardiac infarct area. On the contrary, LNA-antimiR-1 treatment significantly attenuated cardiac ischemia/reperfusion injury. The expression of PKCε and HSP60 was significantly repressed by miR-1 and enhanced by miR-1 knockdown, which may be a molecular mechanism for the role miR-1 in cardiac injury. Moreover, luciferase assay confirmed the direct regulation of miR-1 on protein kinase C epsilon (PKCε and heat shock protein 60 (HSP60. In summary, this study demonstrated that miR-1 is a causal factor for cardiac injury and systemic LNA-antimiR-1 therapy is effective in ameliorating the problem.

  11. MIQuant--semi-automation of infarct size assessment in models of cardiac ischemic injury.

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    Diana S Nascimento

    Full Text Available BACKGROUND: The cardiac regenerative potential of newly developed therapies is traditionally evaluated in rodent models of surgically induced myocardial ischemia. A generally accepted key parameter for determining the success of the applied therapy is the infarct size. Although regarded as a gold standard method for infarct size estimation in heart ischemia, histological planimetry is time-consuming and highly variable amongst studies. The purpose of this work is to contribute towards the standardization and simplification of infarct size assessment by providing free access to a novel semi-automated software tool. The acronym MIQuant was attributed to this application. METHODOLOGY/PRINCIPAL FINDINGS: Mice were subject to permanent coronary artery ligation and the size of chronic infarcts was estimated by area and midline-length methods using manual planimetry and with MIQuant. Repeatability and reproducibility of MIQuant scores were verified. The validation showed high correlation (r(midline length = 0.981; r(area = 0.970 and agreement (Bland-Altman analysis, free from bias for midline length and negligible bias of 1.21% to 3.72% for area quantification. Further analysis demonstrated that MIQuant reduced by 4.5-fold the time spent on the analysis and, importantly, MIQuant effectiveness is independent of user proficiency. The results indicate that MIQuant can be regarded as a better alternative to manual measurement. CONCLUSIONS: We conclude that MIQuant is a reliable and an easy-to-use software for infarct size quantification. The widespread use of MIQuant will contribute towards the standardization of infarct size assessment across studies and, therefore, to the systematization of the evaluation of cardiac regenerative potential of emerging therapies.

  12. MIQuant – Semi-Automation of Infarct Size Assessment in Models of Cardiac Ischemic Injury

    Science.gov (United States)

    Esteves, Tiago; de Pina, Maria de Fátima; Guedes, Joana G.; Freire, Ana; Quelhas, Pedro; Pinto-do-Ó, Perpétua

    2011-01-01

    Background The cardiac regenerative potential of newly developed therapies is traditionally evaluated in rodent models of surgically induced myocardial ischemia. A generally accepted key parameter for determining the success of the applied therapy is the infarct size. Although regarded as a gold standard method for infarct size estimation in heart ischemia, histological planimetry is time-consuming and highly variable amongst studies. The purpose of this work is to contribute towards the standardization and simplification of infarct size assessment by providing free access to a novel semi-automated software tool. The acronym MIQuant was attributed to this application. Methodology/Principal Findings Mice were subject to permanent coronary artery ligation and the size of chronic infarcts was estimated by area and midline-length methods using manual planimetry and with MIQuant. Repeatability and reproducibility of MIQuant scores were verified. The validation showed high correlation (rmidline length = 0.981; rarea = 0.970 ) and agreement (Bland-Altman analysis), free from bias for midline length and negligible bias of 1.21% to 3.72% for area quantification. Further analysis demonstrated that MIQuant reduced by 4.5-fold the time spent on the analysis and, importantly, MIQuant effectiveness is independent of user proficiency. The results indicate that MIQuant can be regarded as a better alternative to manual measurement. Conclusions We conclude that MIQuant is a reliable and an easy-to-use software for infarct size quantification. The widespread use of MIQuant will contribute towards the standardization of infarct size assessment across studies and, therefore, to the systematization of the evaluation of cardiac regenerative potential of emerging therapies. PMID:21980376

  13. MIQuant--semi-automation of infarct size assessment in models of cardiac ischemic injury.

    Science.gov (United States)

    Nascimento, Diana S; Valente, Mariana; Esteves, Tiago; de Pina, Maria de Fátima; Guedes, Joana G; Freire, Ana; Quelhas, Pedro; Pinto-do-Ó, Perpétua

    2011-01-01

    The cardiac regenerative potential of newly developed therapies is traditionally evaluated in rodent models of surgically induced myocardial ischemia. A generally accepted key parameter for determining the success of the applied therapy is the infarct size. Although regarded as a gold standard method for infarct size estimation in heart ischemia, histological planimetry is time-consuming and highly variable amongst studies. The purpose of this work is to contribute towards the standardization and simplification of infarct size assessment by providing free access to a novel semi-automated software tool. The acronym MIQuant was attributed to this application. Mice were subject to permanent coronary artery ligation and the size of chronic infarcts was estimated by area and midline-length methods using manual planimetry and with MIQuant. Repeatability and reproducibility of MIQuant scores were verified. The validation showed high correlation (r(midline length) = 0.981; r(area) = 0.970 ) and agreement (Bland-Altman analysis), free from bias for midline length and negligible bias of 1.21% to 3.72% for area quantification. Further analysis demonstrated that MIQuant reduced by 4.5-fold the time spent on the analysis and, importantly, MIQuant effectiveness is independent of user proficiency. The results indicate that MIQuant can be regarded as a better alternative to manual measurement. We conclude that MIQuant is a reliable and an easy-to-use software for infarct size quantification. The widespread use of MIQuant will contribute towards the standardization of infarct size assessment across studies and, therefore, to the systematization of the evaluation of cardiac regenerative potential of emerging therapies.

  14. Feasibility and safety of Reveal LINQ insertion in a sterile procedure room versus electrophysiology laboratory.

    Science.gov (United States)

    Wong, Geoffrey R; Lau, Dennis H; Middeldorp, Melissa E; Harrington, Judith A; Stolcman, Simon; Wilson, Lauren; Twomey, Darragh J; Kumar, Sharath; Munawar, Dian A; Khokhar, Kashif B; Mahajan, Rajiv; Sanders, Prashanthan

    2016-11-15

    Insertable cardiac monitors (ICMs) are increasingly utilized for diagnosis of unexplained syncope and arrhythmia monitoring. The Reveal LINQ is a novel miniaturized ICM with improved algorithms. The feasibility and safety of insertion outside the traditional electrophysiology laboratory is unknown. Here we compare outcomes of Reveal LINQ insertion in different environments. We report on a prospective, single-centre, non-randomized, observational experience of consecutive Reveal LINQ implantation in the electrophysiology laboratory or a procedure room between October 2013 and October 2015. Of 178 consecutive patients who underwent LINQ device insertion, 80 were implanted in the electrophysiology laboratory and 98 in a procedure room. There were no significant differences in baseline patient characteristics. All implants were performed in the recommended manufacturer method with the exception of 1 which required suture closure. Only a minority received peri-procedural antibiotics with a greater number in the electrophysiology laboratory group (11 [14%] versus 1 [1%], p=0.007). Overall, there were 3 (1.7%) complications with no significant difference between the electrophysiology laboratory and the procedure room groups (2 [3%] versus 1 [1%], p=0.45). There was 1 superficial infection in the procedure room group and 1 superficial infection with device extrusion and 1 traumatic extrusion in the electrophysiology laboratory group. Procedure room implantation subjectively improved laboratory efficiency and patient flow. Reveal LINQ insertion can be safely performed outside of the cardiac laboratory provided a sterile technique is followed by the operator using manufacturer recommendations for insertion. These findings have significant resource implications for hospitals undertaking such procedures. Crown Copyright © 2016. Published by Elsevier Ireland Ltd. All rights reserved.

  15. A computational model-based validation of Guyton's analysis of cardiac output and venous return curves

    Science.gov (United States)

    Mukkamala, R.; Cohen, R. J.; Mark, R. G.

    2002-01-01

    Guyton developed a popular approach for understanding the factors responsible for cardiac output (CO) regulation in which 1) the heart-lung unit and systemic circulation are independently characterized via CO and venous return (VR) curves, and 2) average CO and right atrial pressure (RAP) of the intact circulation are predicted by graphically intersecting the curves. However, this approach is virtually impossible to verify experimentally. We theoretically evaluated the approach with respect to a nonlinear, computational model of the pulsatile heart and circulation. We developed two sets of open circulation models to generate CO and VR curves, differing by the manner in which average RAP was varied. One set applied constant RAPs, while the other set applied pulsatile RAPs. Accurate prediction of intact, average CO and RAP was achieved only by intersecting the CO and VR curves generated with pulsatile RAPs because of the pulsatility and nonlinearity (e.g., systemic venous collapse) of the intact model. The CO and VR curves generated with pulsatile RAPs were also practically independent. This theoretical study therefore supports the validity of Guyton's graphical analysis.

  16. Dysfunctional cardiac mitochondrial bioenergetic, lipidomic, and signaling in a murine model of Barth syndrome.

    Science.gov (United States)

    Kiebish, Michael A; Yang, Kui; Liu, Xinping; Mancuso, David J; Guan, Shaoping; Zhao, Zhongdan; Sims, Harold F; Cerqua, Rebekah; Cade, W Todd; Han, Xianlin; Gross, Richard W

    2013-05-01

    Barth syndrome is a complex metabolic disorder caused by mutations in the mitochondrial transacylase tafazzin. Recently, an inducible tafazzin shRNA knockdown mouse model was generated to deconvolute the complex bioenergetic phenotype of this disease. To investigate the underlying cause of hemodynamic dysfunction in Barth syndrome, we interrogated the cardiac structural and signaling lipidome of this mouse model as well as its myocardial bioenergetic phenotype. A decrease in the distribution of cardiolipin molecular species and robust increases in monolysocardiolipin and dilysocardiolipin were demonstrated. Additionally, the contents of choline and ethanolamine glycerophospholipid molecular species containing precursors for lipid signaling at the sn-2 position were altered. Lipidomic analyses revealed specific dysregulation of HETEs and prostanoids, as well as oxidized linoleic and docosahexaenoic metabolites. Bioenergetic interrogation uncovered differential substrate utilization as well as decreases in Complex III and V activities. Transgenic expression of cardiolipin synthase or iPLA2γ ablation in tafazzin-deficient mice did not rescue the observed phenotype. These results underscore the complex nature of alterations in cardiolipin metabolism mediated by tafazzin loss of function. Collectively, we identified specific lipidomic, bioenergetic, and signaling alterations in a murine model that parallel those of Barth syndrome thereby providing novel insights into the pathophysiology of this debilitating disease.

  17. A computational model-based validation of Guyton's analysis of cardiac output and venous return curves

    Science.gov (United States)

    Mukkamala, R.; Cohen, R. J.; Mark, R. G.

    2002-01-01

    Guyton developed a popular approach for understanding the factors responsible for cardiac output (CO) regulation in which 1) the heart-lung unit and systemic circulation are independently characterized via CO and venous return (VR) curves, and 2) average CO and right atrial pressure (RAP) of the intact circulation are predicted by graphically intersecting the curves. However, this approach is virtually impossible to verify experimentally. We theoretically evaluated the approach with respect to a nonlinear, computational model of the pulsatile heart and circulation. We developed two sets of open circulation models to generate CO and VR curves, differing by the manner in which average RAP was varied. One set applied constant RAPs, while the other set applied pulsatile RAPs. Accurate prediction of intact, average CO and RAP was achieved only by intersecting the CO and VR curves generated with pulsatile RAPs because of the pulsatility and nonlinearity (e.g., systemic venous collapse) of the intact model. The CO and VR curves generated with pulsatile RAPs were also practically independent. This theoretical study therefore supports the validity of Guyton's graphical analysis.

  18. Quantification of the uncertainty in coronary CTA plaque measurements using dynamic cardiac phantom and 3D-printed plaque models

    Science.gov (United States)

    Richards, Taylor; Sturgeon, Gregory M.; Ramirez-Giraldo, Juan Carlos; Rubin, Geoffrey; Segars, Paul; Samei, Ehsan

    2017-03-01

    The purpose of this study was to quantify the accuracy of coronary computed tomography angiography (CTA) stenosis measurements using newly developed physical coronary plaque models attached to a base dynamic cardiac phantom (Shelley Medical DHP-01). Coronary plaque models (5 mm diameter, 50% stenosis, and 32 mm long) were designed and 3D-printed with tissue equivalent materials (calcified plaque with iodine enhanced lumen). Realistic cardiac motion was achieved by fitting known cardiac motion vectors to left ventricle volume-time curves to create synchronized heart motion profiles executed by the base cardiac phantom. Realistic coronary CTA acquisition was accomplished by synthesizing corresponding ECG waveforms for gating and reconstruction purposes. All scans were acquired using a retrospective gating technique on a dual-source CT system (Siemens SOMATOM FLASH) with 75ms temporal resolution. Multi-planar reformatted images were reconstructed along vessel centerlines and the enhanced lumens were manually segmented by 5 independent operators. On average, the stenosis measurement accuracy was 0.9% positive bias for the motion free condition (0 bpm). The measurement accuracy monotonically decreased to 18.5% negative bias at 90 bpm. Contrast-tonoise (CNR), vessel circularity, and segmentation conformity also decreased monotonically with increasing heart rate. These results demonstrate successful implementation of the base cardiac phantom with 3D-printed coronary plaque models, adjustable motion profiles, and coordinated ECG waveforms. They further show the utility of the model to ascertain metrics of coronary CT accuracy and image quality under a variety of plaque, motion, and acquisition conditions.

  19. A predictive model to identify patients with suspected acute coronary syndromes at high risk of cardiac arrest or in-hospital mortality: An IMMEDIATE Trial sub-study

    Directory of Open Access Journals (Sweden)

    Madhab Ray

    2015-12-01

    Conclusions: The multivariable predictive model developed identified patients with very early ACS at high risk of cardiac arrest or death. Using this model could assist treating those with greatest potential benefit from GIK.

  20. Electrophysiological and morphological properties of neurons in the prepositus hypoglossi nucleus that express both ChAT and VGAT in a double-transgenic rat model.

    Science.gov (United States)

    Saito, Yasuhiko; Zhang, Yue; Yanagawa, Yuchio

    2015-04-01

    Although it has been proposed that neurons that contain both acetylcholine (ACh) and γ-aminobutyric acid (GABA) are present in the prepositus hypoglossi nucleus (PHN), these neurons have not been characterized because of the difficulty in identifying them. In the present study, PHN neurons that express both choline acetyltransferase and the vesicular GABA transporter (VGAT) were identified using double-transgenic rats, in which the cholinergic and inhibitory neurons express the fluorescent proteins tdTomato and Venus, respectively. To characterize the neurons that express both tdTomato and Venus (D+ neurons), the afterhyperpolarization (AHP) profiles and firing patterns of these neurons were investigated via whole-cell recordings of brainstem slice preparations. Regarding the three AHP profiles and four firing patterns that the D+ neurons exhibited, an AHP with an afterdepolarization and a firing pattern that exhibited a delay in the generation of the first spike were the preferential properties of these neurons. In the three morphological types classified, the multipolar type that exhibited radiating dendrites was predominant among the D+ neurons. Immunocytochemical analysis revealed that the VGAT-immunopositive axonal boutons that expressed tdTomato were primarily located in the dorsal cap of inferior olive (IO) and the PHN. Although the PHN receives cholinergic inputs from the pedunculopontine tegmental nucleus and laterodorsal tegmental nucleus, D+ neurons were absent from these brain areas. Together, these results suggest that PHN neurons that co-express ACh and GABA exhibit specific electrophysiological and morphological properties, and innervate the dorsal cap of the IO and the PHN.

  1. A 2D Electromechanical Model of Human Atrial Tissue Using the Discrete Element Method.

    Science.gov (United States)

    Brocklehurst, Paul; Adeniran, Ismail; Yang, Dongmin; Sheng, Yong; Zhang, Henggui; Ye, Jianqiao

    2015-01-01

    Cardiac tissue is a syncytium of coupled cells with pronounced intrinsic discrete nature. Previous models of cardiac electromechanics often ignore such discrete properties and treat cardiac tissue as a continuous medium, which has fundamental limitations. In the present study, we introduce a 2D electromechanical model for human atrial tissue based on the discrete element method (DEM). In the model, single-cell dynamics are governed by strongly coupling the electrophysiological model of Courtemanche et al. to the myofilament model of Rice et al. with two-way feedbacks. Each cell is treated as a viscoelastic body, which is physically represented by a clump of nine particles. Cell aggregations are arranged so that the anisotropic nature of cardiac tissue due to fibre orientations can be modelled. Each cell is electrically coupled to neighbouring cells, allowing excitation waves to propagate through the tissue. Cell-to-cell mechanical interactions are modelled using a linear contact bond model in DEM. By coupling cardiac electrophysiology with mechanics via the intracellular Ca(2+) concentration, the DEM model successfully simulates the conduction of cardiac electrical waves and the tissue's corresponding mechanical contractions. The developed DEM model is numerically stable and provides a powerful method for studying the electromechanical coupling problem in the heart.

  2. Optimized Heart Sampling and Systematic Evaluation of Cardiac Therapies in Mouse Models of Ischemic Injury: Assessment of Cardiac Remodeling and Semi-Automated Quantification of Myocardial Infarct Size.

    Science.gov (United States)

    Valente, Mariana; Araújo, Ana; Esteves, Tiago; Laundos, Tiago L; Freire, Ana G; Quelhas, Pedro; Pinto-do-Ó, Perpétua; Nascimento, Diana S

    2015-12-02

    Cardiac therapies are commonly tested preclinically in small-animal models of myocardial infarction. Following functional evaluation, post-mortem histological analysis is essential to assess morphological and molecular alterations underlying the effectiveness of treatment. However, non-methodical and inadequate sampling of the left ventricle often leads to misinterpretations and variability, making direct study comparisons unreliable. Protocols are provided for representative sampling of the ischemic mouse heart followed by morphometric analysis of the left ventricle. Extending the use of this sampling to other types of in situ analysis is also illustrated through the assessment of neovascularization and cellular engraftment in a cell-based therapy setting. This is of interest to the general cardiovascular research community as it details methods for standardization and simplification of histo-morphometric evaluation of emergent heart therapies. © 2015 by John Wiley & Sons, Inc. Copyright © 2015 John Wiley & Sons, Inc.

  3. A new magneto-cardiogram study using a vector model with a virtual heart and the boundary element method

    Science.gov (United States)

    Zhang, Chen; Shou, Guo-Fa; Lu, Hong; Hua, Ning; Tang, Xue-Zheng; Xia, Ling; Ma, Ping; Tang, Fa-Kuan

    2013-09-01

    A cardiac vector model is presented and verified, and then the forward problem for cardiac magnetic fields and electric potential are discussed based on this model and the realistic human torso volume conductor model, including lungs. A torso—cardiac vector model is used for a 12-lead electrocardiographic (ECG) and magneto-cardiogram (MCG) simulation study by using the boundary element method (BEM). Also, we obtain the MCG wave picture using a compound four-channel HTc·SQUID system in a magnetically shielded room. By comparing the simulated results and experimental results, we verify the cardiac vector model and then do a preliminary study of the forward problem of MCG and ECG. Therefore, the results show that the vector model is reasonable in cardiac electrophysiology.

  4. Spreading of excitation in 3-D models of the anisotropic cardiac tissue. I. Validation of the eikonal model.

    Science.gov (United States)

    Franzone, P C; Guerri, L

    1993-02-01

    In this work we investigate, by means of numerical simulations, the performance of two mathematical models describing the spread of excitation in a three dimensional block representing anisotropic cardiac tissue. The first model is characterized by a reaction-diffusion system in the transmembrane and extracellular potentials v and u. The second model is derived from the first by means of a perturbation technique. It is characterized by an eikonal equation, nonlinear and elliptic in the activation time psi(x). The level surfaces psi(x) = t represent the wave-front positions. The numerical procedures based on the two models were applied to test functions and to excitation processes elicited by local stimulations in a relatively small block. The results are in excellent agreement, and for the same problem the computation time required by the eikonal equation is a small fraction of that needed for the reaction-diffusion system. Thus we have strong evidence that the eikonal equation provides a reliable and numerically efficient model of the excitation process. Moreover, numerical simulations have been performed to validate an approximate model for the extracellular potential based on knowledge of the excitation sequence. The features of the extracellular potential distribution affected by the anisotropic conductivity of the medium were investigated.

  5. Modeling beta-adrenergic control of cardiac myocyte contractility in silico

    Science.gov (United States)

    Saucerman, Jeffrey J.; Brunton, Laurence L.; Michailova, Anushka P.; McCulloch, Andrew D.; McCullough, A. D. (Principal Investigator)

    2003-01-01

    The beta-adrenergic signaling pathway regulates cardiac myocyte contractility through a combination of feedforward and feedback mechanisms. We used systems analysis to investigate how the components and topology of this signaling network permit neurohormonal control of excitation-contraction coupling in the rat ventricular myocyte. A kinetic model integrating beta-adrenergic signaling with excitation-contraction coupling was formulated, and each subsystem was validated with independent biochemical and physiological measurements. Model analysis was used to investigate quantitatively the effects of specific molecular perturbations. 3-Fold overexpression of adenylyl cyclase in the model allowed an 85% higher rate of cyclic AMP synthesis than an equivalent overexpression of beta 1-adrenergic receptor, and manipulating the affinity of Gs alpha for adenylyl cyclase was a more potent regulator of cyclic AMP production. The model predicted that less than 40% of adenylyl cyclase molecules may be stimulated under maximal receptor activation, and an experimental protocol is suggested for validating this prediction. The model also predicted that the endogenous heat-stable protein kinase inhibitor may enhance basal cyclic AMP buffering by 68% and increasing the apparent Hill coefficient of protein kinase A activation from 1.0 to 2.0. Finally, phosphorylation of the L-type calcium channel and phospholamban were found sufficient to predict the dominant changes in myocyte contractility, including a 2.6x increase in systolic calcium (inotropy) and a 28% decrease in calcium half-relaxation time (lusitropy). By performing systems analysis, the consequences of molecular perturbations in the beta-adrenergic signaling network may be understood within the context of integrative cellular physiology.

  6. A generalized finite difference method for modeling cardiac electrical activation on arbitrary, irregular computational meshes.

    Science.gov (United States)

    Trew, Mark L; Smaill, Bruce H; Bullivant, David P; Hunter, Peter J; Pullan, Andrew J

    2005-12-01

    A generalized finite difference (GFD) method is presented that can be used to solve the bi-domain equations modeling cardiac electrical activity. Classical finite difference methods have been applied by many researchers to the bi-domain equations. However, these methods suffer from the limitation of requiring computational meshes that are structured and orthogonal. Finite element or finite volume methods enable the bi-domain equations to be solved on unstructured meshes, although implementations of such methods do not always cater for meshes with varying element topology. The GFD method solves the bi-domain equations on arbitrary and irregular computational meshes without any need to specify element basis functions. The method is useful as it can be easily applied to activation problems using existing meshes that have originally been created for use by finite element or finite difference methods. In addition, the GFD method employs an innovative approach to enforcing nodal and non-nodal boundary conditions. The GFD method performs effectively for a range of two and three-dimensional test problems and when computing bi-domain electrical activation moving through a fully anisotropic three-dimensional model of canine ventricles.

  7. Does Parsonnet scoring model predict mortality following adult cardiac surgery in India?

    Directory of Open Access Journals (Sweden)

    Moningi Srilata

    2015-01-01

    Full Text Available Aims and Objectives: To validate the Parsonnet scoring model to predict mortality following adult cardiac surgery in Indian scenario. Materials and Methods: A total of 889 consecutive patients undergoing adult cardiac surgery between January 2010 and April 2011 were included in the study. The Parsonnet score was determined for each patient and its predictive ability for in-hospital mortality was evaluated. The validation of Parsonnet score was performed for the total data and separately for the sub-groups coronary artery bypass grafting (CABG, valve surgery and combined procedures (CABG with valve surgery. The model calibration was performed using Hosmer-Lemeshow goodness of fit test and receiver operating characteristics (ROC analysis for discrimination. Independent predictors of mortality were assessed from the variables used in the Parsonnet score by multivariate regression analysis. Results: The overall mortality was 6.3% (56 patients, 7.1% (34 patients for CABG, 4.3% (16 patients for valve surgery and 16.2% (6 patients for combined procedures. The Hosmer-Lemeshow statistic was <0.05 for the total data and also within the sub-groups suggesting that the predicted outcome using Parsonnet score did not match the observed outcome. The area under the ROC curve for the total data was 0.699 (95% confidence interval 0.62-0.77 and when tested separately, it was 0.73 (0.64-0.81 for CABG, 0.79 (0.63-0.92 for valve surgery (good discriminatory ability and only 0.55 (0.26-0.83 for combined procedures. The independent predictors of mortality determined for the total data were low ejection fraction (odds ratio [OR] - 1.7, preoperative intra-aortic balloon pump (OR - 10.7, combined procedures (OR - 5.1, dialysis dependency (OR - 23.4, and re-operation (OR - 9.4. Conclusions: The Parsonnet score yielded a good predictive value for valve surgeries, moderate predictive value for the total data and for CABG and poor predictive value for combined procedures.

  8. Low Cardiac Output Leads Hepatic Fibrosis in Right Heart Failure Model Rats.

    Directory of Open Access Journals (Sweden)

    Yoshitaka Fujimoto

    Full Text Available Hepatic fibrosis progresses with right heart failure, and becomes cardiac cirrhosis in a severe case. Although its causal factor still remains unclear. Here we evaluated the progression of hepatic fibrosis using a pulmonary artery banding (PAB-induced right heart failure model and investigated whether cardiac output (CO is responsible for the progression of hepatic fibrosis.Five-week-old Sprague-Dawley rats divided into the PAB and sham-operated control groups. After 4 weeks from operation, we measured CO by echocardiography, and hepatic fibrosis ratio by pathological examination using a color analyzer. In the PAB group, CO was significantly lower by 48% than that in the control group (78.2±27.6 and 150.1±31.2 ml/min, P<0.01. Hepatic fibrosis ratio and serum hyaluronic acid, an index of hepatic fibrosis, were significantly increased in the PAB group than those in the control group (7.8±1.7 and 1.0±0.2%, P<0.01, 76.2±27.5 and 32.7±7.5 ng/ml, P<0.01. Notably, the degree of hepatic fibrosis significantly correlated a decrease in CO. Immunohistological analysis revealed that hepatic stellate cells were markedly activated in hypoxic areas, and HIF-1α positive hepatic cells were increased in the PAB group. Furthermore, by real-time PCR analyses, transcripts of profibrotic and fibrotic factors (TGF-β1, CTGF, procollargen I, procollargen III, MMP 2, MMP 9, TIMP 1, TIMP 2 were significantly increased in the PAB group. In addition, western blot analyses revealed that the protein level of HIF-1α was significantly increased in the PAB group than that in the control group (2.31±0.84 and 1.0±0.18 arbitrary units, P<0.05.Our study demonstrated that low CO and tissue hypoxia were responsible for hepatic fibrosis in right failure heart model rats.

  9. Use of human stem cell derived cardiomyocytes to examine sunitinib mediated cardiotoxicity and electrophysiological alterations

    Energy Technology Data Exchange (ETDEWEB)

    Cohen, J.D., E-mail: jennifer.cohen@roche.com [Early and Investigative Safety, Nonclinical Safety, Hoffmann-La Roche, 340 Kingsland Street, Nutley, NJ 07110 (United States); Babiarz, J.E., E-mail: joshua.babiarz@roche.com [Early and Investigative Safety, Nonclinical Safety, Hoffmann-La Roche, 340 Kingsland Street, Nutley, NJ 07110 (United States); Abrams, R.M., E-mail: rory.abrams@roche.com [Early and Investigative Safety, Nonclinical Safety, Hoffmann-La Roche, 340 Kingsland Street, Nutley, NJ 07110 (United States); Guo, L., E-mail: liang.guo@roche.com [Early and Investigative Safety, Nonclinical Safety, Hoffmann-La Roche, 340 Kingsland Street, Nutley, NJ 07110 (United States); Kameoka, S., E-mail: sei.kameoka@roche.com [Early and Investigative Safety, Nonclinical Safety, Hoffmann-La Roche, 340 Kingsland Street, Nutley, NJ 07110 (United States); Chiao, E., E-mail: eric.chiao@roche.com [Early and Investigative Safety, Nonclinical Safety, Hoffmann-La Roche, 340 Kingsland Street, Nutley, NJ 07110 (United States); Taunton, J., E-mail: taunton@cmp.ucsf.edu [Howard Hughes Medical Institute, Cellular and Molecular Pharmacology, University California San Francisco, San Francisco, CA 94158 (United States); Kolaja, K.L., E-mail: kyle.kolaja@roche.com [Early and Investigative Safety, Nonclinical Safety, Hoffmann-La Roche, 340 Kingsland Street, Nutley, NJ 07110 (United States)

    2011-11-15

    Sunitinib, an oral tyrosine kinase inhibitor approved to treat advanced renal cell carcinoma and gastrointestinal stroma tumor, is associated with clinical cardiac toxicity. Although the precise mechanism of sunitinib cardiotoxicity is not known, both the key metabolic energy regulator, AMP-activated protein kinase (AMPK), and ribosomal S 6 kinase (RSK) have been hypothesized as causative, albeit based on rodent models. To study the mechanism of sunitinib-mediated cardiotoxicity in a human model, induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) having electrophysiological and contractile properties of native cardiac tissue were investigated. Sunitinib was cardiotoxic in a dose-dependent manner with an IC{sub 50} in the low micromolar range, observed by a loss of cellular ATP, an increase in oxidized glutathione, and induction of apoptosis in iPSC-CMs. Pretreatment of iPSC-CMs with AMPK activators AICAR or metformin, increased the phosphorylation of pAMPK-T172 and pACC-S79, but only marginally attenuated sunitinib mediated cell death. Furthermore, additional inhibitors of AMPK were not directly cytotoxic to iPSC-CMs up to 250 {mu}M concentrations. Inhibition of RSK with a highly specific, irreversible, small molecule inhibitor (RSK-FMK-MEA) did not induce cytotoxicity in iPSC-CMs below 250 {mu}M. Extensive electrophysiological analysis of sunitinib and RSK-FMK-MEA mediated conduction effects were performed. Taken together, these findings suggest that inhibition of AMPK and RSK are not a major component of sunitinib-induced cardiotoxicity. Although the exact mechanism of cardiotoxicity of sunitinib is not known, it is likely due to inhibition of multiple kinases simultaneously. These data highlight the utility of human iPSC-CMs in investigating the potential molecular mechanisms underlying drug-induced cardiotoxicity. -- Highlights: Black-Right-Pointing-Pointer Cytoxic effect of sunitinib on human stem cell derived cardiomyocytes Black

  10. Testing a longitudinal integrated self-efficacy and self-determination theory model for physical activity post-cardiac rehabilitation

    Directory of Open Access Journals (Sweden)

    Shane N. Sweet

    2014-01-01

    Full Text Available Self-determination theory and self-efficacy theory are prominent theories in the physical activity literature, and studies have begun integrating their concepts. Sweet, Fortier, Strachan and Blanchard (2012 have integrated these two theories in a cross-sectional study. Therefore, this study sought to test a longitudinal integrated model to predict physical activity at the end of a 4-month cardiac rehabilitation program based on theory, research and Sweet et al.’s cross-sectional model. Participants from two cardiac rehabilitation programs (N=109 answered validated self-report questionnaires at baseline, two and four months. Data were analyzed using Amos to assess the path analysis and model fit. Prior to integration, perceived competence and self-efficacy were combined, and labeled as confidence. After controlling for 2-month physical activity and cardiac rehabilitation site, no motivational variables significantly predicted residual change in 4-month physical activity. Although confidence at two months did not predict residual change in 4-month physical activity, it had a strong positive relationship with 2-month physical activity (β=0.30, P<0.001. The overall model retained good fit indices. In conclusion, results diverged from theoretical predictions of physical activity, but self-determination and self-efficacy theory were still partially supported. Because the model had good fit, this study demonstrated that theoretical integration is feasible.

  11. Antivenom Evaluation by Electrophysiological Analysis

    Science.gov (United States)

    Restano-Cassulini, Rita; Garcia, Walter; Paniagua-Solís, Jorge F.; Possani, Lourival D.

    2017-01-01

    Scorpion stings on humans are medically relevant because they may contain toxins that specifically target ion channels. During antivenom production, pharmaceutical companies must use a large number of experimental animals to ensure the antivenom’s efficacy according to pharmacopeia methods. Here we present an electrophysiological alternative for the evaluation of horse antivenoms produced against two species of Moroccan scorpions: Buthus mardochei and Androctonus mauretanicus. Human sodium and potassium channels and acetylcholine nicotinic receptors were analyzed by standard patch-clamp techniques. The results showed that the antivenom is capable of reversing ion current disruption caused by the venom application. We propose the use of this in vitro technique for antivenom evaluation as an alternative to using a large number of live animals. PMID:28241514

  12. Antivenom Evaluation by Electrophysiological Analysis

    Directory of Open Access Journals (Sweden)

    Rita Restano-Cassulini

    2017-02-01

    Full Text Available Scorpion stings on humans are medically relevant because they may contain toxins that specifically target ion channels. During antivenom production, pharmaceutical companies must use a large number of experimental animals to ensure the antivenom’s efficacy according to pharmacopeia methods. Here we present an electrophysiological alternative for the evaluation of horse antivenoms produced against two species of Moroccan scorpions: Buthus mardochei and Androctonus mauretanicus. Human sodium and potassium channels and acetylcholine nicotinic receptors were analyzed by standard patch-clamp techniques. The results showed that the antivenom is capable of reversing ion current disruption caused by the venom application. We propose the use of this in vitro technique for antivenom evaluation as an alternative to using a large number of live animals.

  13. Cardiac Ventricular HIFU: Convergence of Experiment and Theory in the Canine Model

    Science.gov (United States)

    Muratore, Robert; Abe, Yukio; Homma, Shunichi; Bernardi, Richard; Kalisz, Andrew; Feleppa, Ernest J.

    2007-05-01

    OBJECTIVE: HIFU is a promising technique for treating cardiac ventricular diseases such as sustained ventricular tachycardia. Ablations can potentially destroy arrhythmogenic foci and block reentrant circuits. Towards this end, we have learned to control HIFU lesions in the canine model in vivo. METHODS: Experiment — Thoracotomies were performed on anesthetized dogs, following IACUC guidelines. In this open-chest configuration, a polyethylene water-filled bag was coupled to the myocardium with degassed ultrasound gel. The transducer was lowered into the water. Ventricular locations were targeted and insonified with multiple 200-ms HIFU bursts of 60-W acoustic power; the bursts were triggered with the electrocardiogram QRS complex. The therapeutic transducer was a 35-mm focal length, 33-mm diameter PZT annular array, excited at 5.25 MHz. Its -3dB focal region dimensions were 2.5 mm axially and 0.3 mm transversely. A confocal diagnostic transducer was used for aiming and for recording backscattered radiofrequency ultrasound data. Theory — A comprehensive acoustic model has been developed. Individual modules numerically simulate physical processes such as ultrasound beam propagation, energy transfer, and heat flow within tissue. One set of modules simulates HIFU ablation in moving tissue. Tissue motion was obtained from digitized B-mode videos of transverse cross sections of a beating canine heart. Epicardial and endocardial surface positions were extracted from the video frames. Additional simulations of static tissue compared linear and nonlinear propagation models. RESULTS: Significant agreement between simulated and measured lesion sizes and between linear and nonlinear propagation models was demonstrated.

  14. Dietary salt restriction improves cardiac and adipose tissue pathology independently of obesity in a rat model of metabolic syndrome.

    Science.gov (United States)

    Hattori, Takuya; Murase, Tamayo; Takatsu, Miwa; Nagasawa, Kai; Matsuura, Natsumi; Watanabe, Shogo; Murohara, Toyoaki; Nagata, Kohzo

    2014-12-02

    Metabolic syndrome (MetS) enhances salt sensitivity of blood pressure and is an important risk factor for cardiovascular disease. The effects of dietary salt restriction on cardiac pathology associated with metabolic syndrome remain unclear. We investigated whether dietary salt restriction might ameliorate cardiac injury in DahlS.Z-Lepr(fa)/Lepr(fa) (DS/obese) rats, which are derived from a cross between Dahl salt-sensitive and Zucker rats and represent a model of metabolic syndrome. DS/obese rats were fed a normal-salt (0.36% NaCl in chow) or low-salt (0.0466% NaCl in chow) diet from 9 weeks of age and were compared with similarly treated homozygous lean littermates (DahlS.Z-Lepr(+)/Lepr(+), or DS/lean rats). DS/obese rats fed the normal-salt diet progressively developed hypertension and showed left ventricular hypertrophy, fibrosis, and diastolic dysfunction at 15 weeks. Dietary salt restriction attenuated all of these changes in DS/obese rats. The levels of cardiac oxidative stress and inflammation and the expression of cardiac renin-angiotensin-aldosterone system genes were increased in DS/obese rats fed the normal-salt diet, and dietary salt restriction downregulated these parameters in both DS/obese and DS/lean rats. In addition, dietary salt restriction attenuated the increase in visceral adipose tissue inflammation and the decrease in insulin signaling apparent in DS/obese rats without reducing body weight or visceral adipocyte size. Dietary salt restriction did not alter fasting serum glucose levels but it markedly decreased the fasting serum insulin concentration in DS/obese rats. Dietary salt restriction not only prevents hypertension and cardiac injury but also ameliorates insulin resistance, without reducing obesity, in this model of metabolic syndrome. © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  15. Functional identification of islet cell types by electrophysiological fingerprinting

    Science.gov (United States)

    Zhang, Quan; Vergari, Elisa; Kellard, Joely A.; Rodriguez, Blanca; Ashcroft, Frances M.; Rorsman, Patrik

    2017-01-01

    The α-, β- and δ-cells of the pancreatic islet exhibit different electrophysiological features. We used a large dataset of whole-cell patch-clamp recordings from cells in intact mouse islets (N = 288 recordings) to investigate whether it is possible to reliably identify cell type (α, β or δ) based on their electrophysiological characteristics. We quantified 15 electrophysiological variables in each recorded cell. Individually, none of the variables could reliably distinguish the cell types. We therefore constructed a logistic regression model that included all quantified variables, to determine whether they could together identify cell type. The model identified cell type with 94% accuracy. This model was applied to a dataset of cells recorded from hyperglycaemic βV59M mice; it correctly identified cell type in all cells and was able to distinguish cells that co-expressed insulin and glucagon. Based on this revised functional identification, we were able to improve conductance-based models of the electrical activity in α-cells and generate a model of δ-cell electrical activity. These new models could faithfully emulate α- and δ-cell electrical activity recorded experimentally. PMID:28275121

  16. Toward microendoscopy-inspired cardiac optogenetics in vivo: technical overview and perspective

    Science.gov (United States)

    Klimas, Aleksandra; Entcheva, Emilia

    2014-08-01

    The ability to perform precise, spatially localized actuation and measurements of electrical activity in the heart is crucial in understanding cardiac electrophysiology and devising new therapeutic solutions for control of cardiac arrhythmias. Current cardiac imaging techniques (i.e. optical mapping) employ voltage- or calcium-sensitive fluorescent dyes to visualize the electrical signal propagation through cardiac syncytium in vitro or in situ with very high-spatiotemporal resolution. The extension of optogenetics into the cardiac field, where cardiac tissue is genetically altered to express light-sensitive ion channels allowing electrical activity to be elicited or suppressed in a precise cell-specific way, has opened the possibility for all-optical interrogation of cardiac electrophysiology. In vivo application of cardiac optogenetics faces multiple challenges and necessitates suitable optical systems employing fiber optics to actuate and sense electrical signals. In this technical perspective, we present a compendium of clinically relevant access routes to different parts of the cardiac electrical conduction system based on currently employed catheter imaging systems and determine the quantitative size constraints for endoscopic cardiac optogenetics. We discuss the relevant technical advancements in microendoscopy, cardiac imaging, and optogenetics and outline the strategies for combining them to create a portable, miniaturized fiber-based system for all-optical interrogation of cardiac electrophysiology in vivo.

  17. Celecoxib aggravates cardiac apoptosis in L-NAME-induced pressure overload model in rats: Immunohistochemical determination of cardiac caspase-3, Mcl-1, Bax and Bcl-2.

    Science.gov (United States)

    Mosaad, Sarah M; Zaitone, Sawsan A; Ibrahim, Abdelazim; El-Baz, Amani A; Abo-Elmatty, Dina M; Moustafa, Yasser M

    2017-06-25

    The mechanism of celecoxib cardiovascular adverse events was earlier investigated; yet in-depth investigations are needed to assess the involvement of its pro-apoptotic effect throughout this process. An in-vivo chronic rat model of pressure overload employing Nʷ-nitro-l-arginine methyl ester (L-NAME) was tested at different time intervals to ensure the occurrence of persistent myocardial apoptosis along with pressure overload. Seven groups of male Wistar rats were assigned as (i) distilled water; (ii-iv) L-NAME (60 mg/kg) for 6, 12 or 16 weeks; (v-vii) L-NAME [16 weeks] + celecoxib (25, 50 or 100 mg/kg), from week 13 to week 16. Treatment with L-NAME for 6, 12 or 16 weeks increased systolic blood pressure, serum level of creatine kinase-MB and lactate dehydrogenase. Further, it induced cardiac hypertrophy, detected in terms of greater heart weight index and cardiomyocyte cross-sectional area and produced interstitial and perivascular fibrosis. Moreover, administration of L-NAME increased cardiac immunostaining for activated caspase-3 and Bax/Bcl-2 ratio whereas; immunostaining for Mcl-1 was decreased. Administration of celecoxib (25, 50 or 100 mg/kg) aggravated the L-NAME-induced toxicity. The work results shed the light on the putative pro-apoptotic effect of celecoxib at a risk state of pressure overload comparable to the clinical condition of essential hypertension. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Regional evidence of modulation of cardiac adiponectin level in dilated cardiomyopathy: pilot study in a porcine animal model

    Directory of Open Access Journals (Sweden)

    Caselli Chiara

    2012-11-01

    Full Text Available Abstract Background The role of systemic and myocardial adiponectin (ADN in dilated cardiomyopathy is still debated. We tested the regulation of both systemic and myocardial ADN and the relationship with AMP-activated protein kinase (AMPK activity in a swine model of non-ischemic dilated cardiomyopathy. Methods and results Cardiac tissue was collected from seven instrumented adult male minipigs by pacing the left ventricular (LV free wall (180 beats/min, 3 weeks, both from pacing (PS and opposite sites (OS, and from five controls. Circulating ADN levels were inversely related to global and regional cardiac function. Myocardial ADN in PS was down-regulated compared to control (p Conclusions Paradoxically, circulating ADN did not show any cardioprotective effect, confirming its role as negative prognostic biomarker of heart failure. Myocardial ADN was reduced in PS compared to control in an AMPK-independent fashion, suggesting the occurrence of novel mechanisms by which reduced cardiac ADN levels may regionally mediate the decline of cardiac function.

  19. Nebivolol Ameliorates Cardiac NLRP3 Inflammasome Activation in a Juvenile-Adolescent Animal Model of Diet-Induced Obesity

    Science.gov (United States)

    Xie, Qihai; Wei, Tong; Huang, Chenglin; Liu, Penghao; Sun, Mengwei; Shen, Weili; Gao, Pingjin

    2016-01-01

    NLRP3 is involved in obesity-induced cardiac remodeling and dysfunction. In this study, we evaluated whether the cardiac protective effects of nebivolol relied on attenuating NLRP3 activation in a juvenile-adolescent animal model of diet-induced obesity. Weaning male Sprague-Dawley rats were fed with either a standard chow diet (ND) or a high-fat diet (HFD) for 8 weeks. The obese rats were subsequently subdivided into three groups: 1) HFD control group; 2) HFD with low-dose nebivolol (5 mg/kg/d); 3) HFD with high-dose nebivolol (10 mg/kg/d). Treatment with nebivolol prevented HFD-induced obesity associated excess cardiac lipid accumulation as well as myocardial mitochondrial dysfunction. Nebivolol attenuated pro-inflammatory cytokines secretion and NLRP3 inflammasome activation in myocardium of obese rats. In parallel, nebivolol treatment of obese animals increased cardiac β3-AR expression, reversing the reduction of endothelial nitric oxide synthase (eNOS). In vitro, nebivolol treatment of palmitate-incubated H9C2 cells suppressed autophagy, restored mitochondrial biogenesis, leading to decreased mitochondrial reactive oxygen species (mtROS) generation, and suppressed NLRP3 inflammasome activation. Meanwhile the presence of shRNA against β3-AR or against eNOS deteriorated the protective effects of nebivolol. These data suggest the beneficial effect of nebivolol on myocardial lipotoxicity contributing to inhibiting NLRP3 inflammasome activation possibly via improved mitochondrial dysfunction. PMID:27686325

  20. Non-invasive volumetric optoacoustic imaging of cardiac cycles in acute myocardial infarction model in real-time

    Science.gov (United States)

    Lin, Hasiao-Chun Amy; Déan-Ben, Xosé Luís.; Kimm, Melanie; Kosanke, Katja; Haas, Helena; Meier, Reinhard; Lohöfer, Fabian; Wildgruber, Moritz; Razansky, Daniel

    2017-03-01

    Extraction of murine cardiac functional parameters on a beat-by-beat basis remains challenging with the existing imaging modalities. Novel methods enabling in vivo characterization of functional parameters at a high temporal resolution are poised to advance cardiovascular research and provide a better understanding of the mechanisms underlying cardiac diseases. We present a new approach based on analyzing contrast-enhanced optoacoustic (OA) images acquired at high volumetric frame rate without using cardiac gating or other approaches for motion correction. Acute myocardial infarction was surgically induced in murine models, and the method was modified to optimize for acquisition of artifact-free optoacoustic data. Infarcted hearts could be differentiated from healthy controls based on a significantly higher pulmonary transit time (PTT: infarct 2.07 s vs. healthy 1.34 s), while no statistically significant difference was observed in the heart rate (318 bpm vs. 309 bpm). In combination with the proven ability of optoacoustics to track targeted probes within the injured myocardium, our method is capable of depicting cardiac anatomy, function, and molecular signatures on a beat-by-beat basis, both with high spatial and temporal resolution, thus providing new insights into the study of myocardial ischemia.

  1. DNA methylation in an engineered heart tissue model of cardiac hypertrophy: common signatures and effects of DNA methylation inhibitors.

    Science.gov (United States)

    Stenzig, Justus; Hirt, Marc N; Löser, Alexandra; Bartholdt, Lena M; Hensel, Jan-Tobias; Werner, Tessa R; Riemenschneider, Mona; Indenbirken, Daniela; Guenther, Thomas; Müller, Christian; Hübner, Norbert; Stoll, Monika; Eschenhagen, Thomas

    2016-01-01

    DNA methylation affects transcriptional regulation and constitutes a drug target in cancer biology. In cardiac hypertrophy, DNA methylation may control the fetal gene program. We therefore investigated DNA methylation signatures and their dynamics in an in vitro model of cardiac hypertrophy based on engineered heart tissue (EHT). We exposed EHTs from neonatal rat cardiomyocytes to a 12-fold increased afterload (AE) or to phenylephrine (PE 20 µM) and compared DNA methylation signatures to control EHT by pull-down assay and DNA methylation microarray. A 7-day intervention sufficed to induce contractile dysfunction and significantly decrease promoter methylation of hypertrophy-associated upregulated genes such as Nppa (encoding ANP) and Acta1 (α-skeletal actin) in both intervention groups. To evaluate whether pathological consequences of AE are affected by inhibiting de novo DNA methylation we applied AE in the absence and presence of DNA methyltransferase (DNMT) inhibitors: 5-aza-2'-deoxycytidine (aza, 100 µM, nucleosidic inhibitor), RG108 (60 µM, non-nucleosidic) or methylene disalicylic acid (MDSA, 25 µM, non-nucleosidic). Aza had no effect on EHT function, but RG108 and MDSA partially prevented the detrimental consequences of AE on force, contraction and relaxation velocity. RG108 reduced AE-induced Atp2a2 (SERCA2a) promoter methylation. The results provide evidence for dynamic DNA methylation in cardiac hypertrophy and warrant further investigation of the potential of DNA methylation in the treatment of cardiac hypertrophy.

  2. Quantitative modeling of the accuracy in registering preoperative patient-specific anatomic models into left atrial cardiac ablation procedures

    Energy Technology Data Exchange (ETDEWEB)

    Rettmann, Maryam E., E-mail: rettmann.maryam@mayo.edu; Holmes, David R.; Camp, Jon J.; Cameron, Bruce M.; Robb, Richard A. [Biomedical Imaging Resource, Mayo Clinic College of Medicine, Rochester, Minnesota 55905 (United States); Kwartowitz, David M. [Department of Bioengineering, Clemson University, Clemson, South Carolina 29634 (United States); Gunawan, Mia [Department of Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington D.C. 20057 (United States); Johnson, Susan B.; Packer, Douglas L. [Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota 55905 (United States); Dalegrave, Charles [Clinical Cardiac Electrophysiology, Cardiology Division Hospital Sao Paulo, Federal University of Sao Paulo, 04024-002 Brazil (Brazil); Kolasa, Mark W. [David Grant Medical Center, Fairfield, California 94535 (United States)

    2014-02-15

    Purpose: In cardiac ablation therapy, accurate anatomic guidance is necessary to create effective tissue lesions for elimination of left atrial fibrillation. While fluoroscopy, ultrasound, and electroanatomic maps are important guidance tools, they lack information regarding detailed patient anatomy which can be obtained from high resolution imaging techniques. For this reason, there has been significant effort in incorporating detailed, patient-specific models generated from preoperative imaging datasets into the procedure. Both clinical and animal studies have investigated registration and targeting accuracy when using preoperative models; however, the effect of various error sources on registration accuracy has not been quantitatively evaluated. Methods: Data from phantom, canine, and patient studies are used to model and evaluate registration accuracy. In the phantom studies, data are collected using a magnetically tracked catheter on a static phantom model. Monte Carlo simulation studies were run to evaluate both baseline errors as well as the effect of different sources of error that would be present in a dynamicin vivo setting. Error is simulated by varying the variance parameters on the landmark fiducial, physical target, and surface point locations in the phantom simulation studies. In vivo validation studies were undertaken in six canines in which metal clips were placed in the left atrium to serve as ground truth points. A small clinical evaluation was completed in three patients. Landmark-based and combined landmark and surface-based registration algorithms were evaluated in all studies. In the phantom and canine studies, both target registration error and point-to-surface error are used to assess accuracy. In the patient studies, no ground truth is available and registration accuracy is quantified using point-to-surface error only. Results: The phantom simulation studies demonstrated that combined landmark and surface-based registration improved

  3. Software and Hardware Infrastructure for Research in Electrophysiology

    Directory of Open Access Journals (Sweden)

    Roman eMouček

    2014-03-01

    Full Text Available As in other areas of experimental science, operation of electrophysiological laboratory, design and performance of electrophysiological experiments, collection, storage and sharing of experimental data and metadata, analysis and interpretation of these data, and publication of results are time consuming activities. If these activities are well organized and supported by a suitable infrastructure, work efficiency of researchers increases significantly.This article deals with the main concepts, design, and development of software and hardware infrastructure for research in electrophysiology. The described infrastructure has been primarily developed for the needs of neuroinformatics laboratory at the University of West Bohemia, the Czech Republic. However, from the beginning it has been also designed and developed to be open and applicable in laboratories that do similar research.After introducing the laboratory and the whole architectural concept the individual parts of the infrastructure are described. The central element of the software infrastructure is a web-based portal that enables community researchers to store, share, download and search data and metadata from electrophysiological experiments. The data model, domain ontology and usage of semantic web languages and technologies are described. Current data publication policy used in the portal is briefly introduced. The registration of the portal within Neuroscience Information Framework is described. Then the methods used for processing of electrophysiological signals are presented. The specific modifications of these methods introduced by laboratory researches are summarized; the methods are organized into a laboratory workflow. Other parts of the software infrastructure include mobile and offline solutions for data/metadata storing and a hardware stimulator communicating with an EEG amplifier and recording software.

  4. Software and hardware infrastructure for research in electrophysiology.

    Science.gov (United States)

    Mouček, Roman; Ježek, Petr; Vařeka, Lukáš; Rondík, Tomáš; Brůha, Petr; Papež, Václav; Mautner, Pavel; Novotný, Jiří; Prokop, Tomáš; Stěbeták, Jan

    2014-01-01

    As in other areas of experimental science, operation of electrophysiological laboratory, design and performance of electrophysiological experiments, collection, storage and sharing of experimental data and metadata, analysis and interpretation of these data, and publication of results are time consuming activities. If these activities are well organized and supported by a suitable infrastructure, work efficiency of researchers increases significantly. This article deals with the main concepts, design, and development of software and hardware infrastructure for research in electrophysiology. The described infrastructure has been primarily developed for the needs of neuroinformatics laboratory at the University of West Bohemia, the Czech Republic. However, from the beginning it has been also designed and developed to be open and applicable in laboratories that do similar research. After introducing the laboratory and the whole architectural concept the individual parts of the infrastructure are described. The central element of the software infrastructure is a web-based portal that enables community researchers to store, share, download and search data and metadata from electrophysiological experiments. The data model, domain ontology and usage of semantic web languages and technologies are described. Current data publication policy used in the portal is briefly introduced. The registration of the portal within Neuroscience Information Framework is described. Then the methods used for processing of electrophysiological signals are presented. The specific modifications of these methods introduced by laboratory researches are summarized; the methods are organized into a laboratory workflow. Other parts of the software infrastructure include mobile and offline solutions for data/metadata storing and a hardware stimulator communicating with an EEG amplifier and recording software.

  5. When the clock strikes: Modeling the relation between circadian rhythms and cardiac arrhythmias

    CERN Document Server

    Seenivasan, Pavithraa; Sridhar, S; Sinha, Sitabhra

    2016-01-01

    It has recently been observed that the occurrence of sudden cardiac death has a close statistical relationship with the time of day, viz., ventricular fibrillation is most likely to occur between 12 am-6 am, with 6 pm-12 am being the next most likely period. Consequently there has been significant interest in understanding how cardiac activity is influenced by the circadian clock, i.e., temporal oscillations in physiological activity with a period close to 24 hours and synchronized with the day-night cycle. Although studies have identified the genetic basis of circadian rhythms at the intracellular level, the mechanisms by which they influence cardiac pathologies are not yet fully understood. Evidence has suggested that diurnal variations in the conductance properties of ion channel proteins that govern the excitation dynamics of cardiac cells may provide the crucial link. In this paper, we investigate the relationship between the circadian rhythm as manifested in modulations of ion channel properties and the...

  6. Electrophysiological effects of hydrogen sulfide on human atrial fibers

    Institute of Scientific and Technical Information of China (English)

    XU Meng; WU Yu-ming; LI Qian; LIU Su; HE Rui-rong

    2011-01-01

    Background It has been reported that endogenous or exogenous hydrogen sulfide (H2S) exerts physiological effects in the vertebrate cardiovascular system.We have also demonstrated that H2S acts as an important regulator of electrophysiological properties in guinea pig papillary muscles and on pacemaker cells in sinoatrial nodes of rabbits.This study was to observe the electrophysiological effects of H2S on human atrial fibers.Methods Human atrial samples were collected during cardiac surgery.Parameters of action potential in human atrial specialized fibers were recorded using a standard intracellular microelectrode technique.Results NaHS (H2S donor) (50,100 and 200 μmol/L) decreased the amplitude of action potential (APA),maximal rate of depolarization (Vmax),velocity of diastolic (phase 4) depolarization (VDD) and rate of pacemaker firing (RPF),and shortened the duration of 90% repolarization (APD90) in a concentration-dependent manner.ATP-sensitive K+ (KATP)channel blocker glibenclamide (Gli,20 μmol/L) partially blocked the effects of NaHS (100 μmol/L) on human atrial fiber cells.The L-type Ca2+ channel agonist Bay K8644 (0.5 μmol/L) also partially blocked the effects of NaHS (100 μmol/L).An inhibitor of cystathionine y-lyase (CSE),DL-propargylglycine (PPG,200 μmol/L),increased APA,Vmax,VDD and RPF,and prolonged APD90.Conclusions H2S exerts a negative chronotropic action and accelerates the repolarization of human atrial specialized fibers,possibly as a result of increases in potassium efflux through the opening of KATP channels and a concomitant decrease in calcium influx.Endogenous H2S may be generated by CSE and act as an important regulator of electrophysiological properties in human atrial fibers.

  7. A Novel Nonlinear Mathematical Model of Thoracic Wall Mechanics During Cardiopulmonary Resuscitation Based on a Porcine Model of Cardiac Arrest.

    Science.gov (United States)

    Jalali, Ali; Simpao, Allan F; Nadkarni, Vinay M; Berg, Robert A; Nataraj, C

    2017-02-01

    Cardiopulmonary resuscitation (CPR) is used widely to rescue cardiac arrest patients, yet some physiological aspects of the procedure remain poorly understood. We conducted this study to characterize the dynamic mechanical properties of the thorax during CPR in a swine model. This is an important step toward determining optimal CPR chest compression mechanics with the goals of improving the fidelity of CPR simulation manikins and ideally chest compression delivery in real-life resuscitations. This paper presents a novel nonlinear model of the thorax that captures the complex behavior of the chest during CPR. The proposed model consists of nonlinear elasticity and damping properties along with frequency dependent hysteresis. An optimization technique was used to estimate the model coefficients for force-compression using data collected from experiments conducted on swine. To track clinically relevant, time-dependent changes of the chest's properties, the data was divided into two time periods, from 1 to 10 min (early) and greater than 10 min (late) after starting CPR. The results showed excellent agreement between the actual and the estimated forces, and energy dissipation due to viscous damping in the late stages of CPR was higher when compared to the earlier stages. These findings provide insight into improving chest compression mechanics during CPR, and may provide the basis for developing CPR simulation manikins that more accurately represent the complex real world changes that occur in the chest during CPR.

  8. Role of Sodium Channel on Cardiac Action Potential

    Directory of Open Access Journals (Sweden)

    S. H. Sabzpoushan

    2012-06-01

    Full Text Available Sudden cardiac death is a major cause of death worldwide. In most cases, it's caused by abnormal action potential propagation that leads to cardiac arrhythmia. The aim of this article is to study the abnormal action potential propagation through sodium ion concentration variations. We use a new electrophysiological model that is both detailed and computationally efficient. This efficient model is based on the partial differential equation method. The central finite difference method is used for numerical solving of the two-dimensional (2D wave propagation equation. Simulations are implemented in two stages, as a single cardiac cell and as a two-dimensional grid of cells. In both stages, the normal action potential formation in case of a single cell and it's normal propagation in case of a two-dimensional grid of cells were simulated with nominal sodium ion conductance. Then, the effect of sodium ion concentration on the action potential signal was studied by reducing the sodium ion conductance. It is concluded that reducing the sodium ion conductance, decreases both passing ability and conduction velocity of the action potential wave front.

  9. High-order finite element methods for cardiac monodomain simulations

    Directory of Open Access Journals (Sweden)

    Kevin P Vincent

    2015-08-01

    Full Text Available Computational modeling of tissue-scale cardiac electrophysiology requires numerically converged solutions to avoid spurious artifacts. The steep gradients inherent to cardiac action potential propagation necessitate fine spatial scales and therefore a substantial computational burden. The use of high-order interpolation methods has previously been proposed for these simulations due to their theoretical convergence advantage. In this study, we compare the convergence behavior of linear Lagrange, cubic Hermite, and the newly proposed cubic Hermite-style serendipity interpolation methods for finite element simulations of the cardiac monodomain equation. The high-order methods reach converged solutions with fewer degrees of freedom and longer element edge lengths than traditional linear elements. Additionally, we propose a dimensionless number, the cell Thiele modulus, as a more useful metric for determining solution convergence than element size alone. Finally, we use the cell Thiele modulus to examine convergence criteria for obtaining clinically useful activation patterns for applications such as patient-specific modeling where the total activation time is known a priori.

  10. Effects of Intraosseous Tibial vs. Intravenous Vasopressin in a Hypovolemic Cardiac Arrest Model

    Directory of Open Access Journals (Sweden)

    Justin Fulkerson, MSN

    2016-03-01

    Full Text Available Introduction: This study compared the effects of vasopressin via tibial intraosseous (IO and intravenous (IV routes on maximum plasma concentration (Cmax, the time to maximum concentration (Tmax, return of spontaneous circulation (ROSC, and time to ROSC in a hypovolemic cardiac arrest model. Methods: This study was a randomized prospective, between-subjects experimental design. A computer program randomly assigned 28 Yorkshire swine to one of four groups: IV (n=7, IO tibia (n=7, cardiopulmonary resuscitation (CPR + defibrillation (n=7, and a control group that received just CPR (n=7. Ventricular fibrillation was induced, and subjects remained in arrest for two minutes. CPR was initiated and 40 units of vasopressin were administered via IO or IV routes. Blood samples were collected at 0.5, 1, 1.5, 2, 2.5, 3, and 4 minutes. CPR and defibrillation were initiated for 20 minutes or until ROSC was achieved. We measured vasopressin concentrations using highperformance liquid chromatography. Results: There was no significant difference between the IO and IV groups relative to achieving ROSC (p=1.0 but a significant difference between the IV compared to the CPR+ defibrillation group (p=0.031 and IV compared to the CPR-only group (p=0.001. There was a significant difference between the IO group compared to the CPR+ defibrillation group (p=0.031 and IO compared to the CPR-only group (p=0.001. There was no significant difference between the CPR + defibrillation group and the CPR group (p=0.127. There was no significant difference in Cmax between the IO and IV groups (p=0.079. The mean ± standard deviation of Cmax of the IO group was 58,709±25,463pg/mL compared to the IV group, which was 106,198±62,135pg/mL. There was no significant difference in mean Tmax between the groups (p=0.084. There were no significant differences in odds of ROSC between the tibial IO and IV groups. Conclusion: Prompt access to the vascular system using the IO route can circumvent

  11. Modelling far field pacing for terminating spiral waves pinned to ischaemic heterogeneities in cardiac tissue

    Science.gov (United States)

    Boccia, E.; Luther, S.; Parlitz, U.

    2017-05-01

    In cardiac tissue, electrical spiral waves pinned to a heterogeneity can be unpinned (and eventually terminated) using electric far field pulses and recruiting the heterogeneity as a virtual electrode. While for isotropic media the process of unpinning is much better understood, the case of an anisotropic substrate with different conductivities in different directions still needs intensive investigation. To study the impact of anisotropy on the unpinning process, we present numerical simulations based on the bidomain formulation of the phase I of the Luo and Rudy action potential model modified due to the occurrence of acute myocardial ischaemia. Simulating a rotating spiral wave pinned to an ischaemic heterogeneity, we compare the success of sequences of far field pulses in the isotropic and the anisotropic case for spirals still in transient or in steady rotation states. Our results clearly indicate that the range of pacing parameters resulting in successful termination of pinned spiral waves is larger in anisotropic tissue than in an isotropic medium. This article is part of the themed issue `Mathematical methods in medicine: neuroscience, cardiology and pathology'.

  12. Rapamycin Prolongs Cardiac Allograft Survival in a Mouse Model by Inducing Myeloid-Derived Suppressor Cells.

    Science.gov (United States)

    Nakamura, T; Nakao, T; Yoshimura, N; Ashihara, E

    2015-09-01

    Mammalian target of rapamycin (mTOR) inhibitors are the main immunosuppressive drugs for organ transplant recipients. Nevertheless, the mechanisms by which mTOR inhibitors induce immunosuppression is not fully understood. Myeloid-derived suppressor cells (MDSCs) maintain host immunity; however, the relationship between mTOR inhibitors and MDSCs is unclear. Here, the results from a murine cardiac transplantation model revealed that rapamycin treatment (3 mg/kg, intraperitoneally on postoperative days 0, 2, 4, and 6) led to the recruitment of MDSCs and increased their expression of inducible nitric oxide synthase (iNOS). Immunohistochemical analysis revealed that rapamycin induced the migration of iNOS-expressing MDSCs into the subintimal space within the allograft vessels, resulting in a significant prolongation of graft survival compared with that in the untreated group (67 days vs. 7 days, respectively). These effects were counterbalanced by the administration of an anti-Gr-1, which reduced allograft survival to 21 days. Moreover, adoptive transcoronary arterial transfer of MDSCs from rapamycin-treated recipients prolonged allograft survival; this increase was reversed by the anti-Gr-1 antibody. Finally, co-administration of rapamycin and a mitogen-activated protein kinase kinase (MEK) inhibitor trametinib reversed rapamycin-mediated MDSC recruitment. Thus, the mTOR and Raf/MEK/extracellular signal regulated kinase (ERK) signaling pathways appear to play an important role in MDSC expansion.

  13. Cardiac mitochondrial damage and biogenesis in a chronic model of type 1 diabetes.

    Science.gov (United States)

    Shen, Xia; Zheng, Shirong; Thongboonkerd, Visith; Xu, Ming; Pierce, William M; Klein, Jon B; Epstein, Paul N

    2004-11-01

    Diabetic cardiomyopathy is a common complication leading to heightened risk of heart failure and death. In the present report, we performed proteomic analysis on total cardiac proteins from the OVE26 mouse model of type 1 diabetes to identify protein changes that may contribute to diabetic cardiomyopathy. This analysis revealed that a surprising high proportion (12 of 20) of the altered proteins that could be identified by mass spectrometry were of mitochondrial origin. All but one of these proteins were upregulated by diabetes. Quantitative RT-PCR, performed for two of these proteins, indicated that part of the upregulation was attributed to increased messenger RNA levels. Morphological study of diabetic hearts showed significantly increased mitochondrial area and number as well as focal regions with severe damage to mitochondria. Diabetic mitochondria also showed reduced respiratory control ratio (9.63 +/- 0.20 vs. 6.13 +/- 0.41, P factor A and two mitochondrial encoded proteins. Taken together, these results show that mitochondria are a primary target in the diabetic heart, probably due to oxidative stress, and that this damage coincides with and may stimulate mitochondrial biogenesis.

  14. Fast implementation for compressive recovery of highly accelerated cardiac cine MRI using the balanced sparse model.

    Science.gov (United States)

    Ting, Samuel T; Ahmad, Rizwan; Jin, Ning; Craft, Jason; Serafim da Silveira, Juliana; Xue, Hui; Simonetti, Orlando P

    2017-04-01

    Sparsity-promoting regularizers can enable stable recovery of highly undersampled magnetic resonance imaging (MRI), promising to improve the clinical utility of challenging applications. However, lengthy computation time limits the clinical use of these methods, especially for dynamic MRI with its large corpus of spatiotemporal data. Here, we present a holistic framework that utilizes the balanced sparse model for compressive sensing and parallel computing to reduce the computation time of cardiac MRI recovery methods. We propose a fast, iterative soft-thresholding method to solve the resulting ℓ1-regularized least squares problem. In addition, our approach utilizes a parallel computing environment that is fully integrated with the MRI acquisition software. The methodology is applied to two formulations of the multichannel MRI problem: image-based recovery and k-space-based recovery. Using measured MRI data, we show that, for a 224 × 144 image series with 48 frames, the proposed k-space-based approach achieves a mean reconstruction time of 2.35 min, a 24-fold improvement compared a reconstruction time of 55.5 min for the nonlinear conjugate gradient method, and the proposed image-based approach achieves a mean reconstruction time of 13.8 s. Our approach can be utilized to achieve fast reconstruction of large MRI datasets, thereby increasing the clinical utility of reconstruction techniques based on compressed sensing. Magn Reson Med 77:1505-1515, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

  15. Testing a Longitudinal Integrated Self-Efficacy and Self-Determination Theory Model for Physical Activity Post-Cardiac Rehabilitation.

    Science.gov (United States)

    Sweet, Shane N; Fortier, Michelle S; Strachan, Shaelyn M; Blanchard, Chris M; Boulay, Pierre

    2014-01-13

    Self-determination theory and self-efficacy theory are prominent theories in the physical activity literature, and studies have begun integrating their concepts. Sweet, Fortier, Strachan and Blanchard (2012) have integrated these two theories in a cross-sectional study. Therefore, this study sought to test a longitudinal integrated model to predict physical activity at the end of a 4-month cardiac rehabilitation program based on theory, research and Sweet et al.'s cross-sectional model. Participants from two cardiac rehabilitation programs (N=109) answered validated self-report questionnaires at baseline, two and four months. Data were analyzed using Amos to assess the path analysis and model fit. Prior to integration, perceived competence and self-efficacy were combined, and labeled as confidence. After controlling for 2-month physical activity and cardiac rehabilitation site, no motivational variables significantly predicted residual change in 4-month physical activity. Although confidence at two months did not predict residual change in 4-month physical activity, it had a strong positive relationship with 2-month physical activity (β=0.30, Pself-efficacy theory were still partially supported. Because the model had good fit, this study demonstrated that theoretical integration is feasible.

  16. Monitoring of immune activation using biochemical changes in a porcine model of cardiac arrest

    Directory of Open Access Journals (Sweden)

    Anton Amann

    2001-01-01

    Full Text Available In animal models, immune activation is often difficult to assess because of the limited availability of specific assays to detect cytokine activities. In human monocytes/macrophages, interferon-γ induces increased production of neopterin and an enhanced activity of indoleamine 2,3-dioxygenase, which degrades tryptophan via the kynurenine pathway. Therefore, monitoring of neopterin concentrations and of tryptophan degradation can serve to detect the extent of T helper cell 1-type immune activation during cellular immune response in humans. In a porcine model of cardiac arrest, we examined the potential use of neopterin measurements and determination of the tryptophan degradation rate as a means of estimating the extent of immune activation. Urinary neopterin concentrations were measured with high-performance liquid chromatography (HPLC and radioimmunoassay (RIA (BRAHMS Diagnostica, Berlin, Germany. Serum and plasma tryptophan and kynurenine concentrations were also determined using HPLC. Serum and urine neopterin concentrations were not detectable with HPLC in these specimens, whereas RIA gave weakly (presumably false positive results. The mean serum tryptophan concentration was 39.0 Ī 6.2 μmol/l, and the mean kynurenine concentration was 0.85 Ī 0.33 μmol/l. The average kynurenine-per-tryptophan quotient in serum was 21.7Ī 8.4 nmol/μmol, and that in plasma was 20.7Ī 9.5 nmol/μmol (n = 7, which corresponds well to normal values in humans. This study provides preliminary data to support the monitoring of tryptophan degradation but not neopterin concentrations as a potential means of detecting immune activation in a porcine model. The kynurenine-per-tryptophan quotient may serve as a short-term measurement of immune activation and hence permit an estimate of the extent of immune activation.

  17. Watermarked cardiac CT image segmentation using deformable models and the Hermite transform

    Science.gov (United States)

    Gomez-Coronel, Sandra L.; Moya-Albor, Ernesto; Escalante-Ramírez, Boris; Brieva, Jorge

    2015-01-01

    Medical image watermarking is an open area for research and is a solution for the protection of copyright and intellectual property. One of the main challenges of this problem is that the marked images should not differ perceptually from the original images allowing a correct diagnosis and authentication. Furthermore, we also aim at obtaining watermarked images with very little numerical distortion so that computer vision tasks such as segmentation of important anatomical structures do not be impaired or affected. We propose a preliminary watermarking application in cardiac CT images based on a perceptive approach that includes a brightness model to generate a perceptive mask and identify the image regions where the watermark detection becomes a difficult task for the human eye. We propose a normalization scheme of the image in order to improve robustness against geometric attacks. We follow a spread spectrum technique to insert an alphanumeric code, such as patient's information, within the watermark. The watermark scheme is based on the Hermite transform as a bio-inspired image representation model. In order to evaluate the numerical integrity of the image data after watermarking, we perform a segmentation task based on deformable models. The segmentation technique is based on a vector-value level sets method such that, given a curve in a specific image, and subject to some constraints, the curve can evolve in order to detect objects. In order to stimulate the curve evolution we introduce simultaneously some image features like the gray level and the steered Hermite coefficients as texture descriptors. Segmentation performance was assessed by means of the Dice index and the Hausdorff distance. We tested different mark sizes and different insertion schemes on images that were later segmented either automatic or manual by physicians.

  18. Cardiac sodium channelopathies.

    Science.gov (United States)

    Amin, Ahmad S; Asghari-Roodsari, Alaleh; Tan, Hanno L

    2010-07-01

    Cardiac sodium channel are protein complexes that are expressed in the sarcolemma of cardiomyocytes to carry a large inward depolarizing current (INa) during phase 0 of the cardiac action potential. The importance of INa for normal cardiac electrical activity is reflected by the high incidence of arrhythmias in cardiac sodium channelopathies, i.e., arrhythmogenic diseases in patients with mutations in SCN5A, the gene responsible for the pore-forming ion-conducting alpha-subunit, or in genes that encode the ancillary beta-subunits or regulatory proteins of the cardiac sodium channel. While clinical and genetic studies have laid the foundation for our understanding of cardiac sodium channelopathies by establishing links between arrhythmogenic diseases and mutations in genes that encode various subunits of the cardiac sodium channel, biophysical studies (particularly in heterologous expression systems and transgenic mouse models) have provided insights into the mechanisms by which INa dysfunction causes disease in such channelopathies. It is now recognized that mutations that increase INa delay <