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https://www.readbyqxmd.com/read/29598867/role-of-stress-kinase-jnk-in-binge-alcohol-evoked-atrial-arrhythmia
#1
Jiajie Yan, Justin K Thomson, Weiwei Zhao, Xianlong Gao, Fei Huang, Biyi Chen, Qingrong Liang, Long-Sheng Song, Michael Fill, Xun Ai
BACKGROUND: Excessive binge alcohol drinking has acute cardiac arrhythmogenic effects, including promotion of atrial fibrillation (AF), which underlies "Holiday Heart Syndrome." The mechanism that couples binge alcohol abuse with AF susceptibility remains unclear. We previously reported stress-activated c-Jun N-terminal kinase (JNK) signaling contributes to AF development. This is interesting because JNK is implicated in alcohol-caused organ malfunction beyond the heart. OBJECTIVES: The purpose of this study was to detail how JNK promotes binge alcohol-evoked susceptibility to AF...
April 3, 2018: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/29354781/suppression-of-arrhythmia-by-enhancing-mitochondrial-ca-2-uptake-in-catecholaminergic-ventricular-tachycardia-models
#2
Maria K Schweitzer, Fabiola Wilting, Simon Sedej, Lisa Dreizehnter, Nathan J Dupper, Qinghai Tian, Alessandra Moretti, Ilaria My, Ohyun Kwon, Silvia G Priori, Karl-Ludwig Laugwitz, Ursula Storch, Peter Lipp, Andreas Breit, Michael Mederos Y Schnitzler, Thomas Gudermann, Johann Schredelseker
Cardiovascular disease-related deaths frequently arise from arrhythmias, but treatment options are limited due to perilous side effects of commonly used antiarrhythmic drugs. Cardiac rhythmicity strongly depends on cardiomyocyte Ca2+ handling and prevalent cardiac diseases are causally associated with perturbations in intracellular Ca2+ handling. Therefore, intracellular Ca2+ transporters are lead candidate structures for novel and safer antiarrhythmic therapies. Mitochondria and mitochondrial Ca2+ transport proteins are important regulators of cardiac Ca2+ handling...
December 2017: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/29352041/stress-signaling-jnk2-crosstalk-with-camkii-underlies-enhanced-atrial-arrhythmogenesis
#3
Jiajie Yan, Weiwei Zhao, Justin K Thomson, Xianlong Gao, Dominic M DeMarco, Elena Carrillo, Biyi Chen, Xiaomin Wu, Kenneth S Ginsburg, Mamdouh Bakhos, Donald M Bers, Mark E Anderson, Long-Sheng Song, Michael Fill, Xun Ai
<u>Rationale:</u> Atrial fibrillation (AF) is the most common arrhythmia and advanced age is an inevitable and predominant AF risk factor. However, the mechanisms that couple aging and AF propensity remain unclear, making targeted therapeutic interventions unattainable. <u>Objective:</u> To explore the functional role of an important stress-response c-Jun N-terminal kinase (JNK) in sarcoplasmic reticulum (SR) Ca2+ handling and consequently Ca2+ -mediated atrial arrhythmias. <u>Methods and Results:</u> We employed a series of cutting-edge electrophysiological and molecular techniques, exploited the power of transgenic mouse models to detail the molecular mechanism, and verified its clinical applicability in parallel studies on donor human hearts...
January 19, 2018: Circulation Research
https://www.readbyqxmd.com/read/29282211/late-ca-2-sparks-and-ripples-during-the-systolic-ca-2-transient-in-heart-muscle-cells
#4
Ewan D Fowler, Cherrie H T Kong, Jules C Hancox, Mark B Cannell
RATIONALE: The development of a refractory period for Ca2+ spark initiation after Ca2+ release in cardiac myocytes should inhibit further Ca2+ release during the action potential plateau. However, Ca2+ release sites that did not initially activate or which have prematurely recovered from refractoriness might release Ca2+ later during the action potential and alter the cell-wide Ca2+ transient. OBJECTIVE: To investigate the possibility of late Ca2+ spark (LCS) activity in intact isolated cardiac myocytes using fast confocal line scanning with improved confocality and signal to noise...
February 2, 2018: Circulation Research
https://www.readbyqxmd.com/read/29217432/transverse-tubular-network-structures-in-the-genesis-of-intracellular-calcium-alternans-and-triggered-activity-in-cardiac-cells
#5
Zhen Song, Michael B Liu, Zhilin Qu
RATIONALE: The major role of a transverse-tubular (TT) network in a cardiac cell is to facilitate effective excitation-contraction coupling and signaling. The TT network structures are heterogeneous within a single cell, and vary between different types of cells and species. They are also remodeled in cardiac diseases. However, how different TT network structures predispose cardiac cells to arrhythmogenesis remains to be revealed. OBJECTIVE: To systematically investigate the roles of TT network structure and the underlying mechanisms in the genesis of intracellular calcium (Ca2+ ) alternans and triggered activity (TA)...
January 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29216239/effects-of-early-afterdepolarizations-on-excitation-patterns-in-an-accurate-model-of-the-human-ventricles
#6
Enid Van Nieuwenhuyse, Gunnar Seemann, Alexander V Panfilov, Nele Vandersickel
Early Afterdepolarizations, EADs, are defined as the reversal of the action potential before completion of the repolarization phase, which can result in ectopic beats. However, the series of mechanisms of EADs leading to these ectopic beats and related cardiac arrhythmias are not well understood. Therefore, we aimed to investigate the influence of this single cell behavior on the whole heart level. For this study we used a modified version of the Ten Tusscher-Panfilov model of human ventricular cells (TP06) which we implemented in a 3D ventricle model including realistic fiber orientations...
2017: PloS One
https://www.readbyqxmd.com/read/29145393/estimating-the-probabilities-of-rare-arrhythmic-events-in-multiscale-computational-models-of-cardiac-cells-and-tissue
#7
Mark A Walker, Viatcheslav Gurev, John J Rice, Joseph L Greenstein, Raimond L Winslow
Ectopic heartbeats can trigger reentrant arrhythmias, leading to ventricular fibrillation and sudden cardiac death. Such events have been attributed to perturbed Ca2+ handling in cardiac myocytes leading to spontaneous Ca2+ release and delayed afterdepolarizations (DADs). However, the ways in which perturbation of specific molecular mechanisms alters the probability of ectopic beats is not understood. We present a multiscale model of cardiac tissue incorporating a biophysically detailed three-dimensional model of the ventricular myocyte...
November 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/29016724/triggered-intracellular-calcium-waves-in-dog-and-human-left-atrial-myocytes-from-normal-and-failing-hearts
#8
Gary L Aistrup, Rishi Arora, Søren Grubb, Shin Yoo, Benjamin Toren, Manvinder Kumar, Aaron Kunamalla, William Marszalec, Tej Motiwala, Shannon Tai, Sean Yamakawa, Satya Yerrabolu, Francisco J Alvarado, Hector H Valdivia, Jonathan M Cordeiro, Yohannes Shiferaw, John Andrew Wasserstrom
Aims: Abnormal intracellular Ca2+ cycling contributes to triggered activity and arrhythmias in the heart. We investigated the properties and underlying mechanisms for systolic triggered Ca2+ waves in left atria from normal and failing dog hearts. Methods and results: Intracellular Ca2+ cycling was studied using confocal microscopy during rapid pacing of atrial myocytes (36 °C) isolated from normal and failing canine hearts (ventricular tachypacing model). In normal atrial myocytes (NAMs), Ca2+ waves developed during rapid pacing at rates ≥ 3...
November 1, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28870222/general-anesthetics-protects-against-cardiac-arrest-induced-brain-injury-by-inhibiting-calcium-wave-propagation-in-zebrafish
#9
Dao-Jie Xu, Bin Wang, Xuan Zhao, Yi Zheng, Jiu-Lin Du, Ying-Wei Wang
Cardiac arrest is a leading cause of death and disability worldwide. Although many victims are initially resuscitated, they often suffer from serious brain injury, even leading to a "persistent vegetative state". Therefore, it is need to explore therapies which restore and protect brain function after cardiac arrest. In the present study, using Tg (HuC:GCaMP5) zebrafish as a model, we found the zebrafish brain generated a burst of Ca(2+) wave after cardiac arrest by in vivo time-lapse confocal imaging. The Ca(2+) wave was firstly initiated at hindbrain and then sequentially propagated to midbrain and telencephalon, the neuron displayed Ca(2+) overload after Ca(2+) wave propagation...
September 4, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28864150/standard-and-strain-measurements-by-echocardiography-detect-early-overloaded-right-ventricular-dysfunction-validation-against-hemodynamic-and-myocyte-contractility-changes-in-a-large-animal-model
#10
Amir Hodzic, Pierre Bobin, Delphine Mika, Mohamed Ly, Florence Lefebvre, Patrick Lechêne, Emmanuel Le Bret, Elodie Gouadon, Mathieu Coblence, Grégoire Vandecasteele, André Capderou, Jérôme Leroy, Catherine Rucker-Martin, Virginie Lambert
BACKGROUND: Early detection of right ventricular (RV) failure is required to improve the management of patients with congenital heart diseases. The aim of this study was to validate echocardiography for the early detection of overloaded RV dysfunction, compared with hemodynamic and myocyte contractility assessment. METHODS: Using a porcine model reproducing repaired tetralogy of Fallot, RV function was evaluated over 4 months using standard echocardiography and speckle-tracking compared with hemodynamic parameters (conductance catheter)...
August 29, 2017: Journal of the American Society of Echocardiography
https://www.readbyqxmd.com/read/28859293/impaired-calcium-homeostasis-is-associated-with-sudden-cardiac-death-and-arrhythmias-in-a-genetic-equivalent-mouse-model-of-the-human-hrc-ser96ala-variant
#11
Christos Tzimas, Daniel M Johnson, Demetrio J Santiago, Elizabeth Vafiadaki, Demetrios A Arvanitis, Constantinos H Davos, Aimilia Varela, Nikolaos C Athanasiadis, Constantinos Dimitriou, Michalis Katsimpoulas, Stephan Sonntag, Mariya Kryzhanovska, Doron Shmerling, Stephan E Lehnart, Karin R Sipido, Evangelia G Kranias, Despina Sanoudou
Aims: The histidine-rich calcium-binding protein (HRC) Ser96Ala variant has previously been identified as a potential biomarker for ventricular arrhythmias and sudden cardiac death in patients with idiopathic dilated cardiomyopathy. Herein, the role of this variant in cardiac pathophysiology is delineated through a novel mouse model, carrying the human mutation in the homologous mouse position. Methods and results: The mouse HRC serine 81, homologous to human HRC serine 96, was mutated to alanine, using knock-in gene targeting...
September 1, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28683095/computer-algorithms-for-automated-detection-and-analysis-of-local-ca2-releases-in-spontaneously-beating-cardiac-pacemaker-cells
#12
Alexander V Maltsev, Sean P Parsons, Mary S Kim, Kenta Tsutsui, Michael D Stern, Edward G Lakatta, Victor A Maltsev, Oliver Monfredi
Local Ca2+ Releases (LCRs) are crucial events involved in cardiac pacemaker cell function. However, specific algorithms for automatic LCR detection and analysis have not been developed in live, spontaneously beating pacemaker cells. In the present study we measured LCRs using a high-speed 2D-camera in spontaneously contracting sinoatrial (SA) node cells isolated from rabbit and guinea pig and developed a new algorithm capable of detecting and analyzing the LCRs spatially in two-dimensions, and in time. Our algorithm tracks points along the midline of the contracting cell...
2017: PloS One
https://www.readbyqxmd.com/read/28268302/role-of-cytosolic-calcium-diffusion-in-cardiac-purkinje-cells
#13
Bijay Limbu, Kushal Shah, Makarand Deo
The Cardiac Purkinje cells (PCs) exhibit distinct calcium (Ca2+) homeostasis than that in ventricular myocytes (VMs). Due to lack of t-tubules in PCs, the Ca2+ ions entering the cell have to diffuse through the cytoplasm to reach the sarcoplasmic reticulum (SR) before triggering Ca2+-induced-Ca2+-release (CICR). In recent experimental studies PCs have been shown to be more susceptible to action potential (AP) abnormalities than the VMs, however the exact mechanisms are poorly understood. In this study, we utilize morphologically realistic detailed biophysical mathematical model of a murine PC to systematically examine the role intracellular Ca2+ diffusion in the APs of PCs...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28164461/flexible-polygon-mirror-based-laser-scanning-microscope-platform-for-multiphoton-in-vivo-imaging
#14
Y X Li, V Gautam, A Brüstle, I A Cockburn, V R Daria, C Gillespie, K Gaus, C Alt, W M Lee
Commercial microscopy systems make use of tandem scanning i.e. either slow or fast scanning. We constructed, for the first time, an advanced control system capable of delivering a dynamic line scanning speed ranging from 2.7 kHz to 27 kHz and achieve variable frame rates from 5 Hz to 50 Hz (512 × 512). The dynamic scanning ability is digitally controlled by a new customized open-source software named PScan1.0. This permits manipulation of scanning rates either to gain higher fluorescence signal at slow frame rate without increasing laser power or increase frame rates to capture high speed events...
February 6, 2017: Journal of Biophotonics
https://www.readbyqxmd.com/read/28056022/l-type-calcium-channel-inhibition-contributes-to-the-proarrhythmic-effects-of-aconitine-in-human-cardiomyocytes
#15
Jianjun Wu, Xiangchong Wang, Ying Ying Chung, Cai Hong Koh, Zhenfeng Liu, Huicai Guo, Qiang Yuan, Chuan Wang, Suwen Su, Heming Wei
Aconitine (ACO) is well-known for causing lethal ventricular tachyarrhythmias. While cardiac Na+ channel opening during repolarization has long been documented in animal cardiac myocytes, the cellular effects and mechanism of ACO in human remain unexplored. This study aimed to assess the proarrhythmic effects of ACO in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). ACO concentration-dependently (0.3 ~ 3.0 μM) shortened the action potentials (AP) durations (APD) in ventricular-like hiPSC-CMs by > 40% and induced delayed after-depolarization...
2017: PloS One
https://www.readbyqxmd.com/read/27739779/nonlinear-onset-of-calcium-wave-propagation-in-cardiac-cells
#16
Yohannes Shiferaw
Spontaneous calcium (Ca) waves in cardiac myocytes are known to underlie a wide range of cardiac arrhythmias. However, it is not understood which physiological parameters determine the onset of waves. In this study, we explore the relationship between Ca signaling between ion channels and the nucleation of Ca waves. In particular, we apply a master equation approach to analyze the stochastic interaction between neighboring clusters of ryanodine receptor (RyR) channels. Using this analysis, we show that signaling between clusters can be described as a barrier hopping process with exponential sensitivity to system parameters...
September 2016: Physical Review. E
https://www.readbyqxmd.com/read/27730696/new-insights-into-the-elucidation-of-angiotensin-1-7-in-vivo-antiarrhythmic-effects-and-its-related-cellular-mechanisms
#17
Julliane Vasconcelos Joviano-Santos, Artur Santos-Miranda, Humberto Cavalcante Joca, Jader Santos Cruz, Anderson José Ferreira
What is the central question of this study? Recently, there have been many studies exploring the biological effects of angiotensin-(1-7), which has been proved to have cardioprotective actions. However, the effects of this peptide on cardiac arrhythmias in vivo and details regarding its mechanism of action are still undetermined. What is the main finding and its importance? We investigated protective effects of angiotensin-(1-7) on cardiac arrhythmias in vivo, which were not properly explored in terms of cellular mechanisms...
December 1, 2016: Experimental Physiology
https://www.readbyqxmd.com/read/27207297/calcium-wave-propagation-triggered-by-local-mechanical-stimulation-as-a-method-for-studying-gap-junctions-and-hemichannels
#18
Jegan Iyyathurai, Bernard Himpens, Geert Bultynck, Catheleyne D'hondt
Intercellular communication is essential for the coordination and synchronization of cellular processes. Gap junction channels play an important role to communicate between cells and organs, including the brain, lung, liver, lens, retina, and heart. Gap junctions enable a direct route for ions like calcium and potassium, and low molecular weight compounds, such as inositol 1,4,5-trisphosphate, cyclic adenosine monophosphate, and various kinds of metabolites to pass between cells. Intercellular calcium wave propagation evoked by a local mechanical stimulus is one of the gap junction assays to study intercellular communication...
2016: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27096943/beta-adrenoceptor-stimulation-reveals-ca2-waves-and-sarcoplasmic-reticulum-ca2-depletion-in-left-ventricular-cardiomyocytes-from-post-infarction-rats-with-and-without-heart-failure
#19
Mani Sadredini, Tore Kristian Danielsen, Jan Magnus Aronsen, Ravinea Manotheepan, Karina Hougen, Ivar Sjaastad, Mathis Korseberg Stokke
Abnormal cellular Ca2+ handling contributes to both contractile dysfunction and arrhythmias in heart failure. Reduced Ca2+ transient amplitude due to decreased sarcoplasmic reticulum Ca2+ content is a common finding in heart failure models. However, heart failure models also show increased propensity for diastolic Ca2+ release events which occur when sarcoplasmic reticulum Ca2+ content exceeds a certain threshold level. Such Ca2+ release events can initiate arrhythmias. In this study we aimed to investigate if both of these aspects of altered Ca2+ homeostasis could be found in left ventricular cardiomyocytes from rats with different states of cardiac function six weeks after myocardial infarction when compared to sham-operated controls...
2016: PloS One
https://www.readbyqxmd.com/read/26851245/calmodulin-kinase-ii-inhibition-limits-the-pro-arrhythmic-ca2-waves-induced-by-camp-phosphodiesterase-inhibitors
#20
Pierre Bobin, Audrey Varin, Florence Lefebvre, Rodolphe Fischmeister, Grégoire Vandecasteele, Jérôme Leroy
AIMS: A major concern of using phosphodiesterase (PDE) inhibitors in heart failure is their potential to increase mortality by inducing arrhythmias. By diminishing cyclic adenosine monophosphate (cAMP) hydrolysis, they promote protein kinase A (PKA) activity under β-adrenergic receptor (β-AR) stimulation, hence enhancing Ca(2+) cycling and contraction. Yet, cAMP also activates CaMKII via PKA or the exchange protein Epac, but it remains unknown whether these pathways are involved in the pro-arrhythmic effect of PDE inhibitors...
May 1, 2016: Cardiovascular Research
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