The Virtual Ventricular Wall: A Tool for Exploring Cardiac Propagation and Arrhythmogenesis

Methods for the experimental and clinical investigation of cardiac arrhythmias are limited to inferring propagation within the myocardium, from surface measurements, or from electrodes at a few sites within the cardiac wall. Biophysically and anatomically detailed computational models of cardiac tissues offer a powerful way for studying the electrical propagation processes and arrhythmias within the virtual heart. We use virtual tissues to study and visualise the effects of patho- and physiological conditions, and pharmacological interventions on transmural propagation in the virtual ventricular walls. Class III drug actions are quantitatively explained by changes induced in the transmural dispersion of action potential duration. We illustrate the automated construction of a virtual anisotropic ventricle from Diffusion Tensor MRI for individual hearts, and use it to explore mechanisms leading to ventricular fibrillation. The virtual ventricular wall provides an effective tool for exploring, evaluating and visualising processes during the initiation and maintenance of ventricular arrhythmias.     

Cardiac channelopathies: Genetic and molecular mechanisms

Channelopathies are diseases caused by dysfunctional ion channels, due to either genetic or acquired pathological factors. Inherited cardiac arrhythmic syndromes are among the most studied human disorders involving ion channels. Since seminal observations made in 1995, thousands of mutations have been found in many of the different genes that code for cardiac ion channel subunits and proteins that regulate the cardiac ion channels. The main phenotypes observed in patients carrying these mutations are congenital long QT syndrome (LQTS), Brugada syndrome (BrS), catecholaminergic polymorphic ventricular tachycardia (CPVT), short QT syndrome (SQTS) and variable types of conduction defects (CD). The goal of this review is to present an update of the main genetic and molecular mechanisms, as well as the associated phenotypes of cardiac channelopathies as of 2012.     

Imaging mass spectrometry reveals characteristic changes in triglyceride and phospholipid species in regenerating mouse liver

After partial hepatectomy (PH), regenerating liver accumulates unknown lipid species. Here, we analyzed lipids in murine liver and adipose tissues following PH by thin-layer chromatography (TLC), imaging mass spectrometry (IMS), and real-time RT-PCR. In liver, IMS revealed that a single TLC band comprised major 19 TG species. Similarly, IMS showed a single phospholipid TLC band to be major 13 species. In adipose tissues, PH induced changes to expression of genes regulating lipid metabolism. Finally, IMS of phosphatidylcholine species demonstrated distribution gradients in lobules that resembled hepatic zonation. IMS is thus a novel and power tool for analyzing lipid species with high resolution.     

利用生物条形码技术对蓝舌病毒VP7蛋白进行微量检测

目的：建立高灵敏检测蓝舌病毒VP7蛋白的生物条形码检测方法。方法：制备VP7蛋白的多抗及特异DNA链标记的金纳米颗粒探针（NP）和VP7蛋白单抗标记的磁性微球探针（MMP）,形成MMP-VP7蛋白-NP三明治复合物后,再利用去杂交将NP探针上标记的DNA链释放出来,通过PCR或芯片检测方法鉴定释放的DNA链,确定VP7蛋白的存在。结果：建立了蓝舌病毒VP7蛋白的生物条形码检测体系,检测灵敏度可达10fg/mL,为常规ELISA检测的106倍。结论：为发展高灵敏度的蓝舌病毒生物条形码检测试剂盒鉴定了基础。     

Enhancement of rural domestic sewage treatment performance, and assessment of microbial community diversity and structure using tower vermifiltration

The performance of a novel three-stage vermifiltration (VF) system using the earthworm, Eisenia fetida, for rural domestic wastewater treatment was studied during a 131-day period. The average removal efficiencies of the tower VF planted with Penstemon campanulatus were as follows: chemical oxygen demand, 81.3%; ammonium, 98%; total nitrogen, 60.2%; total phosphorus, 98.4%; total nitrogen, mainly in the form of nitrate. Soils played an important role in removing the organic matter. The three-sectional design with increasing oxygen demand concentration in the effluents, and the distribution of certain oxides in the padding were likely beneficial for ammonium and phosphorus removal, respectively. The microbial community profiles revealed that band patterns varied more or less in various matrices of each stage at different sampling times, while the presence of earthworms intensified the bacterial diversity in soils. Retrieved sequences recovered from the media in VF primarily belonged to unknown bacterium and Bacilli of Firmicutes.     

Chaotic based reconstructed phase space features for detecting ventricular fibrillation

Among the variety of cardiac arrhythmias, ventricular fibrillation (VF) and ventricular tachycardia (VT) are life-threatening; thus, accurate classification of these arrhythmias is a crucial task for cardiologists. Nevertheless, VT and VF signals are very similar in the time domain and accurate distinguishing these signals with naked eyes in some cases is impossible. In this paper, a novel self-similarity image-based scheme is introduced to classify the underlying information of VT, VF and normal electrocardiogram (ECG) signals. In this study, VT, VF and normal ECG signals are selected from CCU of the Royal Infirmary of Edinburgh and MIT-BIH datasets. According to the time delay method, signal samples can be assigned to state variables and a trajectory can be achieved. To extract the proposed self-similarity feature, first, two different trajectories from each signal trial are drawn according to two different delay time values. The two-dimensional state space of each trial trajectory is considered as an image. Therefore, two trajectory images are produced for each signal. Number of visited pixels in the first image is determined and is subtracted from that of the second image as the self-similarity feature of that signal. Moreover, another scheme is proposed to have a better estimation of self-similarity in which the logical AND operator is applied to both images (matrices) of each ECG trial. The third proposed criterion is similar to box counting method by this difference that each pixel is assigned a weight according to the trajectory density at that point and finally visited weighted pixels are counted. To classify VF from VT and normal ECG, a threshold is determined through the cross validation phase under the Receiver Operating Characteristic (ROC) criterion. To assess the proposed methods, the mentioned signals are classified using the-state-of-art chaotic features such as correlation dimension, the largest Lyapunov exponent and Approximate Entropy (ApEn). Experimental results indicate superiority of the proposed method in classifying the VT, VF and normal ECG signals compared to present traditional schemes. In addition, computational complexity of the introduced methods is very low and can be implemented in real-time applications.     

Intramural conduction system gradients and electrogram regularity during ventricular fibrillation

Introduction

The His-Purkinje system has been shown to harbor triggers for ventricular fibrillation (VF) initiation. However, the substrate responsible for VF maintenance remains elusive. We hypothesized that standard, electrode-based, point-to-point mapping would yield meaningful insight into site-specific patterns and organization which may shed light on the critical substrate for maintenance of VF.

Functional dominant-negative mutation of sodium channel subunit gene SCN3B associated with atrial fibrillation in a Chinese GeneID population

Atrial fibrillation (AF) is the most common cardiac arrhythmia in the clinic, and accounts for more than 15% of strokes. Mutations in cardiac sodium channel α, β1 and β2 subunit genes (SCN5A, SCN1B, and SCN2B) have been identified in AF patients. We hypothesize that mutations in the sodium channel β3 subunit gene SCN3B are also associated with AF. To test this hypothesis, we carried out a large scale sequencing analysis of all coding exons and exon-intron boundaries of SCN3B in 477 AF patients (28.5% lone AF) from the GeneID Chinese Han population. A novel A130V mutation was identified in a 46-year-old patient with lone AF, and the mutation was absent in 500 controls. Mutation A130V dramatically decreased the cardiac sodium current density when expressed in HEK293/Na_v1.5 stable cell line, but did not have significant effect on kinetics of activation, inactivation, and channel recovery from inactivation. When co-expressed with wild type SCN3B, the A130V mutant SCN3B negated the function of wild type SCN3B, suggesting that A130V acts by a dominant negative mechanism. Western blot analysis with biotinylated plasma membrane protein extracts revealed that A130V did not affect cell surface expression of Na_v1.5 or SCN3B, suggesting that mutant A130V SCN3B may not inhibit sodium channel trafficking, instead may affect conduction of sodium ions due to its malfunction as an integral component of the channel complex. This study identifies the first AF-associated mutation in SCN3B, and suggests that mutations in SCN3B may be a new pathogenic cause of AF.     

Mechanisms Underlying the Antifibrillatory Action of Hyperkalemia in Guinea Pig Hearts

Hyperkalemia increases the organization of ventricular fibrillation (VF) and may also terminate it by mechanisms that remain unclear. We previously showed that the left-to-right heterogeneity of excitation and wave fragmentation present in fibrillating guinea pig hearts is mediated by chamber-specific outward conductance differences in the inward rectifier potassium current (I_K1). We hypothesized that hyperkalemia-mediated depolarization of the reversal potential of I_K1 (E_K1) would reduce excitability and thereby reduce VF excitation frequencies and left-to-right heterogeneity. We induced VF in Langendroff-perfused guinea pig hearts and increased the extracellular K⁺ concentration ([K⁺]_o) from control (4 mM) to 7 mM (n = 5) or 10 mM (n = 7). Optical mapping enabled spatial characterization of excitation dominant frequencies (DFs) and wavebreaks, and identification of sustained rotors (>4 cycles). During VF, hyperkalemia reduced the maximum DF of the left ventricle (LV) from 31.5 ± 4.7 Hz (control) to 23.0 ± 4.7 Hz (7.0 mM) or 19.5 ± 3.6 Hz (10.0 mM; p < 0.006), the left-to-right DF gradient from 14.7 ± 3.6 Hz (control) to 4.4 ± 1.3 Hz (7 mM) and 3.2 ± 1.4 Hz (10 mM), the number of DF domains, and the incidence of wavebreak in the LV and interventricular regions. During 10 mM [K⁺]_o, the rotation period and core area of sustained rotors in the LV increased, and VF often terminated. Two-dimensional computer simulations mimicking experimental VF predicted that clamping E_K1 to normokalemic values during simulated hyperkalemia prevented all of the hyperkalemia-induced VF changes. During hyperkalemia, despite the shortening of the action potential duration, depolarization of E_K1 increased refractoriness, leading to a slowing of VF, which effectively superseded the influence of I_K1 conductance differences on VF organization. This reduced the left-to-right excitation gradients and heterogeneous wavebreak formation. Overall, these results provide, to our knowledge, the first direct mechanistic insight into the organization and/or termination of VF by hyperkalemia.