A new algorithm to diagnose atrial ectopic origin from multi lead ECG systems - insights from 3D virtual human atria and torso

Rapid atrial arrhythmias such as atrial fibrillation (AF) predispose to ventricular arrhythmias, sudden cardiac death and stroke. Identifying the origin of atrial ectopic activity from the electrocardiogram (ECG) can help to diagnose the early onset of AF in a cost-effective manner. The complex and rapid atrial electrical activity during AF makes it difficult to obtain detailed information on atrial activation using the standard 12-lead ECG alone. Compared to conventional 12-lead ECG, more detailed ECG lead configurations may provide further information about spatio-temporal dynamics of the body surface potential (BSP) during atrial excitation. We apply a recently developed 3D human atrial model to simulate electrical activity during normal sinus rhythm and ectopic pacing. The atrial model is placed into a newly developed torso model which considers the presence of the lungs, liver and spinal cord. A boundary element method is used to compute the BSP resulting from atrial excitation. Elements of the torso mesh corresponding to the locations of the placement of the electrodes in the standard 12-lead and a more detailed 64-lead ECG configuration were selected. The ectopic focal activity was simulated at various origins across all the different regions of the atria. Simulated BSP maps during normal atrial excitation (i.e. sinoatrial node excitation) were compared to those observed experimentally (obtained from the 64-lead ECG system), showing a strong agreement between the evolution in time of the simulated and experimental data in the P-wave morphology of the ECG and dipole evolution. An algorithm to obtain the location of the stimulus from a 64-lead ECG system was developed. The algorithm presented had a success rate of 93%, meaning that it correctly identified the origin of atrial focus in 75/80 simulations, and involved a general approach relevant to any multi-lead ECG system. This represents a significant improvement over previously developed algorithms

Detecting and Reducing Redundancy in Alarm Networks

Alarm systems are vital for the safe operation of almost all large-scale industrial and technical installations, such as chemical plants or power stations. The optimization of alarm systems has great potential to improve the safety of these installations, and also to increase their profitability through the reduction of automated shut-downs and suboptimal operation modes. In this work we present a new approach to alarm system optimization through the identification of redundant alarms. Our approach is based on a ranking of alarms by their connectivity in the alarm network. We also propose an overall redundancy measure for the alarm system which can be used to monitor performance improvements after redundant alarms have been removed. We present an example demonstrating that our ranking technique provides operational staff with useful information, allowing them to enhance the effectiveness of their existing alarm systems

Electrophysiological models for the heterogeneous canine atria:computational platform for studying rapid atrial arrhythmias

Heterogeneity in the electrical action potential (AP) properties can provide a substrate for atrial arrhythmias, especially at rapid pacing rates. In order to quantify such substrates, we develop a family of detailed AP models for canine atrial cells. An existing model for the canine right atrial (RA) myocyte was modified based on electrophysiological data from dog to create new models for the canine left atrium (LA), the interatrial Bachmann’s bundle (BB), and the pulmonary vein (PV). The heterogeneous AP models were incorporated into a tissue strand model to simulate the AP propagation, and used to quantify conditions for conduction abnormalities (primarily, conduction block at rapid pacing rated) in the canine atria

Optimal Iodine Staining of Cardiac Tissue for X-ray Computed Tomography

X-ray computed tomography (XCT) has been shown to be an effective imaging technique for a variety of materials. Due to the relatively low differential attenuation of X-rays in biological tissue, a high density contrast agent is often required to obtain optimal contrast. The contrast agent, iodine potassium iodide ([Formula: see text]), has been used in several biological studies to augment the use of XCT scanning. Recently I2KI was used in XCT scans of animal hearts to study cardiac structure and to generate 3D anatomical computer models. However, to date there has been no thorough study into the optimal use of I2KI as a contrast agent in cardiac muscle with respect to the staining times required, which has been shown to impact significantly upon the quality of results. In this study we address this issue by systematically scanning samples at various stages of the staining process. To achieve this, mouse hearts were stained for up to 58 hours and scanned at regular intervals of 6-7 hours throughout this process. Optimal staining was found to depend upon the thickness of the tissue; a simple empirical exponential relationship was derived to allow calculation of the required staining time for cardiac samples of an arbitrary size

An image-based model of atrial muscular architecture effects of structural anisotropy on electrical activation

Background— Computer models that capture key features of the heterogeneous myofiber architecture of right and left atria and interatrial septum provide a means of investigating the mechanisms responsible for atrial arrhythmia. The data necessary to implement such models have not previously been available. The aims of this study were to characterize surface geometry and myofiber architecture throughout the atrial chambers and to investigate the effects of this structure on atrial activation. Methods and Results— Atrial surface geometry and myofiber orientations were reconstructed in 3D at 50×50×50-μm 3 resolution from serial images acquired throughout the sheep atrial chambers. Myofiber orientations were determined by Eigen-analysis of the structure tensor. These data have been incorporated into an anatomic model that provides the first quantitative representation of myofiber architecture throughout the atrial chambers. By simulating activation on this 3D structure, we have confirmed the roles of specialized myofiber tracts such as the crista terminalis, pectinate muscles, and the Bachman bundle on the spread of activation from the sinus node. We also demonstrate how the complex myocyte arrangement in the posterior left atrium contributes to activation time dispersion adjacent to the pulmonary veins and increased vulnerability to rhythm disturbance generated by ectopic stimuli originating in the pulmonary vein sleeves. Conclusions— We have developed a structurally detailed, image-based model of atrial anatomy that provides deeper understanding of the role that myocyte architecture plays in normal and abnormal atrial electric function. </jats:sec

Imino sugars inhibit the formation and secretion of bovine viral diarrhea virus, a pestivirus model of hepatitis C virus: Implications for the development of broad spectrum anti-hepatitis virus agents

One function of N-linked glycans is to assist in the folding of glycoproteins by mediating interactions of the lectin-like chaperone proteins calnexin and calreticulin with nascent glycoproteins. These interactions can be prevented by inhibitors of the α-glucosidases, such as N-butyl-deoxynojirimycin (NB-DNJ) and N-nonyl-DNJ (NN-DNJ), and this causes some proteins to be misfolded and retained within the endoplasmic reticulum (ER). We have shown previously that the NN-DNJ-induced misfolding of one of the hepatitis B virus (HBV) envelope glycoproteins prevents the formation and secretion of virus in vitro and that this inhibitor alters glycosylation and reduces the viral levels in an animal model of chronic HBV infection. This led us to investigate the effect of glucosidase inhibitors on another ER-budding virus, bovine viral diarrhea virus, a tissue culture surrogate of human hepatitis C virus (HCV). Here we show that in MDBK cells α-glucosidase inhibitors prevented the formation and secretion of infectious bovine viral diarrhea virus. Data also are presented showing that NN-DNJ, compared with NB-DNJ, exhibits a prolonged retention in liver in vivo. Because viral secretion is selectively hypersensitive to glucosidase inhibition relative to the secretion of cellular proteins, the possibility that glucosidase inhibitors could be used as broad-based antiviral hepatitis agents is discussed. A single drug against HBV, HCV, and, possibly, HDV, which together chronically infect more than 400 million people worldwide, would be of great therapeutic value

Summary of controllable factors and their values used in the study.

<p>Summary of controllable factors and their values used in the study.</p