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Cardiac electrophysiology

Hung X Nguyen, Robert D Kirkton, Nenad Bursac
The ability to directly enhance electrical excitability of human cells is hampered by the lack of methods to efficiently overexpress large mammalian voltage-gated sodium channels (VGSC). Here we describe the use of small prokaryotic sodium channels (BacNav) to create de novo excitable human tissues and augment impaired action potential conduction in vitro. Lentiviral co-expression of specific BacNav orthologues, an inward-rectifying potassium channel, and connexin-43 in primary human fibroblasts from the heart, skin or brain yields actively conducting cells with customizable electrophysiological phenotypes...
October 18, 2016: Nature Communications
Mukund A Prabhu, B V Srinivas Prasad, Anees Thajudeen, Narayanan Namboodiri
INTRODUCTION: Bundle branch reentry as a mechanism of ventricular tachycardia (VT) in endomyocardial fibrosis (EMF) is not described. CASE REPORT: A 52-year-old woman with left ventricular (LV) EMF had VT needing cardioversion. She had mitral regurgitation and left bundle branch block, but no LV dilation or heart failure. During electrophysiological study, clinical VT could be easily induced, and it was confirmed to be bundle branch reentrant VT (BBRVT). She was treated with ablation of the right bundle branch...
September 2016: Indian Heart Journal
Richard A Gray, Pras Pathmanathan
Elucidating the underlying mechanisms of fatal cardiac arrhythmias requires a tight integration of electrophysiological experiments, models, and theory. Existing models of transmembrane action potential (AP) are complex (resulting in over parameterization) and varied (leading to dissimilar predictions). Thus, simpler models are needed to elucidate the "minimal physiological requirements" to reproduce significant observable phenomena using as few parameters as possible. Moreover, models have been derived from experimental studies from a variety of species under a range of environmental conditions (for example, all existing rabbit AP models incorporate a formulation of the rapid sodium current, INa, based on 30 year old data from chick embryo cell aggregates)...
October 2016: PLoS Computational Biology
Natalie Weber, Kristin Schwanke, Stephan Greten, Meike Wendland, Bogdan Iorga, Martin Fischer, Cornelia Geers-Knörr, Jan Hegermann, Christoph Wrede, Jan Fiedler, Henning Kempf, Annika Franke, Birgit Piep, Angelika Pfanne, Thomas Thum, Ulrich Martin, Bernhard Brenner, Robert Zweigerdt, Theresia Kraft
Human pluripotent stem cell (hPSC)-derived cardiomyocytes hold great potential for in vitro modeling of diseases like cardiomyopathies. Yet, knowledge about expression and functional impact of sarcomeric protein isoforms like the myosin heavy chain (MyHC) in hPSC-cardiomyocytes is scarce. We hypothesized that ventricular β-MyHC expression alters contraction and calcium kinetics and drives morphological and electrophysiological differentiation towards ventricular-like cardiomyocytes. To address this, we (1) generated human embryonic stem cell-derived cardiomyocytes (hESC-CMs) that switched towards exclusive β-MyHC, and (2) functionally and morphologically characterized these hESC-CMs at the single-cell level...
November 2016: Basic Research in Cardiology
Torsten Konrad, Sebastian Sonnenschein, Frank Patrick Schmidt, Hanke Mollnau, Karsten Bock, Blanca Quesada Ocete, Thomas Münzel, Cathrin Theis, Thomas Rostock
AIMS: Different cardiac arrhythmias have been suggested to be associated with Danon disease, e.g. Wolff-Parkinson-White syndrome. However, a systematic electrophysiological investigation of patients with Danon disease is lacking thus far. METHODS AND RESULTS: Seven patients with Danon disease (4 males, 35.8 ± 10.8 years; 3 females, 51.3 ± 19.9 years) from 3 different families were studied. In all patients, the presence of Danon disease was confirmed by western blot of biopsy material or genetic testing...
October 14, 2016: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
Ursula Ravens, Katja E Odening
Despite the epidemiological scale of atrial fibrillation, current treatment strategies are of limited efficacy and safety. Ideally, novel drugs should specifically correct the pathophysiological mechanisms responsible for atrial fibrillation with no other cardiac or extracardiac actions. Atrial-selective drugs are directed toward cellular targets with sufficiently different characteristics in atria and ventricles to modify only atrial function. Several potassium (K(+)) channels with either predominant expression in atria or distinct electrophysiological properties in atria and ventricles can serve as atrial-selective drug targets...
October 12, 2016: Pharmacology & Therapeutics
Douglas Wildes, Warren Lee, Bruno Haider, Scott Cogan, Krishnakumar Sundaresan, David Mills, Christopher Yetter, Patrick Hart, Christopher Haun, Mikael Concepcion, Johan Kirkhorn, Marc Bitoun
We developed a 2.5 x 6.6 mm 2D array transducer with integrated transmit/receive ASIC for 4D ICE (real-time 3D IntraCardiac Echocardiography) applications. The ASIC and transducer design were optimized so that the high voltage transmit, low-voltage TGC (time-gain control) and preamp, subaperture beamformer, and digital control circuits for each transducer element all fit within the 0.019 mm2 area of the element. The transducer assembly was deployed in a 10 Fr (3.3 mm diameter) catheter, integrated with a GE Vivid1 E9 ultrasound imaging system, and evaluated in three pre-clinical studies...
October 12, 2016: IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control
Maria Cecilia Gonzalez Corcia, Juan Sieira, Andrea Sarkozy, Carlo de Asmundis, Gian-Battista Chierchia, Jaime Hernandez Ojeda, Gudrun Pappaert, Pedro Brugada
AIMS: To investigate the clinical characteristics, prognoses, and presence of risk factors in young patients with Brugada syndrome (BS). METHODS AND RESULTS: A consecutive cohort of 128 young BS patients (≤25 years old at diagnosis) was analysed. Eighty-eight patients (69%) were asymptomatic, whereas 40 (31%) presented with clinical manifestations of BS. Markers of prognosis and risk were identified upon comparison of these two groups. A history of malignant syncope was strong predictors of ventricular arrhythmic events...
October 13, 2016: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
Takumi Yamada, Harish Doppalapudi, Silvio H Litovsky, H Thomas McElderry, G Neal Kay
BACKGROUND: Radiofrequency catheter ablation (RFCA) of idiopathic ventricular arrhythmias (VAs) originating from the basal portion of the left ventricular (LV) summit, which is divided from the apical LV (A-LV) summit by the great cardiac vein (GCV), is challenging. This study investigated the efficacy of RFCA and electrocardiographic and electrophysiological characteristics of these VAs. METHODS AND RESULTS: Forty-five consecutive patients with symptomatic idiopathic LV summit VAs were studied...
October 2016: Circulation. Arrhythmia and Electrophysiology
Sean D Boothe, Jackson D Myers, Seokwon Pok, Junping Sun, Yutao Xi, Raymond M Nieto, Jie Cheng, Jeffrey G Jacot
The stiffness of myocardial tissue changes significantly at birth and during neonatal development, concurrent with significant changes in contractile and electrical maturation of cardiomyocytes. Previous studies by our group have shown that cardiomyocytes generate maximum contractile force when cultured on a substrate with a stiffness approximating native cardiac tissue. However, effects of substrate stiffness on the electrophysiology and ion currents in cardiomyocytes have not been fully characterized. In this study, neonatal rat ventricular myocytes were cultured on the surface of flat polyacrylamide hydrogels with elastic moduli ranging from 1 to 25 kPa...
October 8, 2016: Cell Biochemistry and Biophysics
Cai-Ying Li, Bu-Lang Gao, Tong Pan, Cheng Xiang, Xue-Jing Zhang, Xiao-Wei Liu, Qiong-Ying Fan
PURPOSE: To quantitatively measure the morphology parameters of the right auricle with 256-slice multidetector computed tomography angiography (MDCTA) in healthy people. MATERIALS AND METHODS: A retrospective analysis of 200 patients who had undergone coronary MDCTA with negative findings was performed. The raw imaging data were reconstructed and the right auricular volume, right atrial volume, right auricle height, base long and short axes, base perimeter and area, normal angle, and distance were quantitatively measured...
October 7, 2016: Surgical and Radiologic Anatomy: SRA
Małgorzata Kowalska, Krzysztof Kocot
Results of epidemiological studies suggest a significant impact of ambient particulate matter air pollution (PM10 and PM2,5) on the health of the population. Increased level of these pollutants is connected with increased rate of daily mortality and hospitalizations due to cardiovascular diseases. Among analyzed health effects, heart arrhythmias and stroke are mentioned most frequently. The aim of the study was to present the current knowledge of potential influence of the exposure to fine particulate matter on the presence of arrhythmias and strokes...
September 28, 2016: Postȩpy Higieny i Medycyny Doświadczalnej
Zhaoye Zhou, Qi Jin, Long Yu, Liqun Wu, Bin He
BACKGROUND: Knowledge of atrial electrophysiological properties is crucial for clinical intervention of atrial arrhythmias and the investigation of the underlying mechanism. This study aims to evaluate the feasibility of a novel noninvasive cardiac electrical imaging technique in imaging bi-atrial activation sequences from body surface potential maps (BSPMs). METHODS: The study includes 7 subjects, with 3 atrial flutter patients, and 4 healthy subjects with normal atrial activations...
2016: PloS One
Pietro Enea Lazzerini, Pier Leopoldo Capecchi, Iacopo Bertolozzi, Gabriella Morozzi, Sauro Lorenzini, Antonella Simpatico, Enrico Selvi, Maria Romana Bacarelli, Maurizio Acampa, Deana Lazaro, Nabil El-Sherif, Mohamed Boutjdir, Franco Laghi-Pasini
Mounting evidence indicates that in chronic inflammatory arthritis (CIA), QTc prolongation is frequent and correlates with systemic inflammatory activation. Notably, basic studies demonstrated that inflammatory cytokines induce profound changes in potassium and calcium channels resulting in a prolonging effect on cardiomyocyte action potential duration, thus on the QT interval on the electrocardiogram. Moreover, it has been demonstrated that in rheumatoid arthritis (RA) patients, the risk of sudden cardiac death is significantly increased when compared to non-RA subjects...
2016: Frontiers in Cardiovascular Medicine
Steven E Williams, Nick W F Linton, Steven Niederer, Mark D O'Neill
AIMS: Complex ablation procedures are supported by accurate representation of an increasing variety of electrophysiological and imaging data within electroanatomic mapping systems (EMS). This study aims to develop a novel method for representing multiple complementary datasets on a single cardiac chamber model. Validation of the system and its application to both atrial and ventricular arrhythmias is examined. METHODS AND RESULTS: Dot mapping was conceived to display multiple datasets by utilizing quantitative surface shading to represent one dataset and finely spaced dots to represent others...
October 4, 2016: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
Gary Tse, Bryan P Yan
Sudden cardiac death, frequently due to ventricular arrhythmias, is a significant problem globally. Most affected individuals do not arrive at hospital in time for medical treatment. Therefore, there is an urgent need to identify the most-at-risk patients for insertion of prophylactic implantable cardioverter defibrillators. Clinical risk markers derived from electrocardiography are important for this purpose. They can be based on repolarization, including corrected QT (QTc) interval, QT dispersion (QTD), interval from the peak to the end of the T-wave (Tpeak - Tend), (Tpeak - Tend)/QT, T-wave alternans (TWA), and microvolt TWA...
October 4, 2016: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
Aditi Khandekar, Steven Springer, Wei Wang, Stephanie Hicks, Carla J Weinheimer, Ramon Diaz-Trelles, Jeanne M Nerbonne, Stacey Rentschler
RATIONALE: Ventricular arrhythmias often arise from the Purkinje-myocyte junction and are a leading cause of sudden cardiac death. Notch activation reprograms cardiac myocytes to an "induced Purkinje-like" state characterized by prolonged action potential duration and expression of Purkinje enriched genes. OBJECTIVE: To understand the mechanism by which canonical Notch signaling causes action potential prolongation. METHODS AND RESULTS: We find that endogenous Purkinje cells have reduced peak K(+) current, Ito and IK,slow when compared with ventricular myocytes...
October 3, 2016: Circulation Research
James Winter, Alexandra R Cook, Dawn H Patient, Stevan R Emmett, John Tattersall, Michael J Shattock
Pre-treatment with reversible acetylcholinesterase (AChE) inhibitors is an effective strategy for reducing lethality following organophosphate nerve agent exposure. AChE inhibition may have unwanted cardiac side effects, which could be negated by adjunctive anti-cholinergic therapy. The aims of the present study were to examine the concentration-dependent effects of physostigmine on cardiac responses to vagus nerve stimulation (VNS), to test whether adjunctive treatment with hyoscine can reverse these effects and to assess the functional interaction and electrophysiological consequences of a combined pre-treatment...
September 28, 2016: Neurotoxicology
Justin Judd, Jonathan Lovas, Guo N Huang
Cultured cardiomyocytes can be used to study cardiomyocyte biology using techniques that are complementary to in vivo systems. For example, the purity and accessibility of in vitro culture enables fine control over biochemical analyses, live imaging, and electrophysiology. Long-term culture of cardiomyocytes offers access to additional experimental approaches that cannot be completed in short term cultures. For example, the in vitro investigation of dedifferentiation, cell cycle re-entry, and cell division has thus far largely been restricted to rat cardiomyocytes, which appear to be more robust in long-term culture...
2016: Journal of Visualized Experiments: JoVE
Beom Seok Kim, Chang-Hee Lee, Gyeong-Eon Chang, Eunji Cheong, Injae Shin
Sirtuin 1 (SIRT1) is known to suppress differentiation of pluripotent/multipotent cells and neural progenitor cells into neurons by blocking activation of transcription factors critical for neurogenesis. EX-527 is a highly selective and potent inhibitor against SIRT1 and has been used as a chemical probe that modulates SIRT1-associated biological processes. However, the effect of EX-527 on neuronal differentiation in pluripotent cells has not been well elucidated. Here, we report an examination of EX-527 effects on neurogenesis of pluripotent P19 cells...
September 29, 2016: Scientific Reports
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