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Ventricular depolarization

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https://www.readbyqxmd.com/read/28202194/study-of-factors-affecting-the-progression-and-termination-of-drug-induced-torsade-de-pointes-in-two-dimensional-cardiac-tissue
#1
Ponnuraj Kirthi Priya, M Ramasubba Reddy
INTRODUCTION: To study the conditions leading to the initiation and termination of drug induced Torsade de pointes (TdP) along with QT prolongation. METHODS: A 2D anisotropic transmural section of the ventricular myocardium is modeled using the TP06 equations and the cells are interconnected with gap junction conductances (GJC). The tissue is remodeled by reducing the repolarization reserve (by increasing calcium current (ICaL)) of all cells thus making them vulnerable to development of early after depolarizations (EADs)...
February 2, 2017: Journal of Electrocardiology
https://www.readbyqxmd.com/read/28184198/local-left-ventricular-epicardial-j-waves-and-late-potentials-in-brugada-syndrome-patients-with-inferolateral-early-repolarization-pattern
#2
Satoshi Nagase, Masamichi Tanaka, Hiroshi Morita, Koji Nakagawa, Tadashi Wada, Masato Murakami, Nobuhiro Nishii, Kazufumi Nakamura, Hiroshi Ito, Tohru Ohe, Kengo F Kusano
Background: Brugada syndrome (BrS) is characterized by J-point or ST-segment elevation on electrocardiograms (ECGs) and increased risk of ventricular fibrillation (VF). In BrS, epicardial depolarization abnormality with delayed potential on the right ventricular outflow tract is reportedly the predominant mechanism underlying VF. Yet VF occurrence is also associated with early repolarization (ER) pattern in the inferolateral ECG leads, which may represent the inferior and/or left lateral ventricular myocardium...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28182562/in-silico-modeling-of-the-functional-role-of-reduced-sialylation-in-sodium-and-potassium-channel-gating-of-mouse-ventricular-myocytes
#3
Dongping Du, Hui Yang, Andrew R Ednie, Eric S Bennett
Cardiac ion channels are highly glycosylated membrane proteins, with up to 30% of the protein's mass containing glycans. Heart diseases often accompany individuals with congenital disorders of glycosylation (CDG). However, cardiac dysfunction among CDG patients is not yet fully understood. There is an urgent need to study how aberrant glycosylation impacts cardiac electrical signaling. Our previous works reported that congenitally reduced sialylation achieved through deletion of the sialyltransferase gene, ST3Gal4, leads to altered gating of voltage-gated Na+ and K+ channels (Nav and Kv, respectively)...
February 6, 2017: IEEE Journal of Biomedical and Health Informatics
https://www.readbyqxmd.com/read/28170198/differential-mechanisms-of-myocardial-conduction-slowing-by-adipose-tissue-derived-stromal-cells-derived-from-different-species
#4
Judith N Ten Sande, Nicoline W Smit, Mojtaba Parvizi, Shirley C M van Amersfoorth, Josée A Plantinga, Pascal F H M van Dessel, Jacques M T de Bakker, Marco C Harmsen, Ruben Coronel
Stem cell therapy is a promising therapeutic option to treat patients after myocardial infarction. However, the intramyocardial administration of large amounts of stem cells might generate a proarrhythmic substrate. Proarrhythmic effects can be explained by electrotonic and/or paracrine mechanisms. The narrow therapeutic time window for cell therapy and the presence of comorbidities limit the application of autologous cell therapy. The use of allogeneic or xenogeneic stem cells is a potential alternative to autologous cells, but differences in the proarrhythmic effects of adipose-derived stromal cells (ADSCs) across species are unknown...
January 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28140304/electrical-approach-to-improve-left-ventricular-activation-during-right-ventricle-stimulation
#5
María Paula Bonomini, Daniel F Ortega, Luis D Barja, Nicolasa Mangani, Analía Paolucci, Emilio Logarzo
Coronary sinus mapping is commonly used to evaluate left atrial activation. Herein, we propose to use it to assess which right ventricular pacing modality produces the shortest left ventricular activation times (R-LVtime) and the narrowest QRS widths. Three study groups were defined: 54 controls without intraventricular conduction disturbances; 15 patients with left bundle branch block, and other 15 with right bundle branch block. Left ventricular activation times and QRS widths were evaluated among groups under sinus rhythm, right ventricular apex, right ventricular outflow tract and high output septal zone (SEPHO)...
2017: Medicina
https://www.readbyqxmd.com/read/28097316/evaluation-of-structural-progression-in-arrhythmogenic-right-ventricular-dysplasia-cardiomyopathy
#6
Thomas P Mast, Cynthia A James, Hugh Calkins, Arco J Teske, Crystal Tichnell, Brittney Murray, Peter Loh, Stuart D Russell, Birgitta K Velthuis, Daniel P Judge, Dennis Dooijes, Ryan J Tedford, Jeroen F van der Heijden, Harikrishna Tandri, Richard N Hauer, Theodore P Abraham, Pieter A Doevendans, Anneline S J M Te Riele, Maarten J Cramer
Importance: Considerable research has described the arrhythmic course of arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C). However, objective data characterizing structural progression, such as ventricular enlargement and cardiac dysfunction, in ARVD/C are relatively scarce. Objectives: To define the extent of structural progression, identify determinants of structural progression, and determine the association between structural progression and electrocardiographic (ECG) changes in patients with ARVD/C...
January 11, 2017: JAMA Cardiology
https://www.readbyqxmd.com/read/28077437/sensitized-signalling-between-l-type-ca2-channels-and-ryanodine-receptors-in-the-absence-or-inhibition-of-fkbp12-6-in-cardiomyocytes
#7
Yan-Ting Zhao, Yun-Bo Guo, Lei Gu, Xue-Xin Fan, Hua-Qian Yang, Zheng Chen, Peng Zhou, Qi Yuan, Guang-Ju Ji, Shi-Qiang Wang
AIMS: The heart contraction is controlled by the Ca(2+)-induced Ca(2+ )release (CICR) between L-type Ca(2+ )channels and ryanodine receptors (RyRs). The FK506-binding protein FKBP12.6 binds to RyR subunits, but its role in stabilizing RyR function has been debated for long. Recent reports of high-resolution RyR structure show that the HD2 domain that binds to the SPRY2 domain of neighbouring subunit in FKBP-bound RyR1 is detached and invisible in FKBP-null RyR2. The present study was to test the consequence of FKBP12...
January 10, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28066827/optimized-left-ventricular-endocardial-stimulation%C3%A2-is-superior-to-optimized-epicardial%C3%A2-stimulation-in-ischemic-patients-with%C3%A2-poor-response-to-cardiac-resynchronization%C3%A2-therapy-a%C3%A2-combined-magnetic-resonance-imaging-electroanatomic%C3%A2-contact-mapping-and-hemodynamic
#8
Jonathan M Behar, Tom Jackson, Eoin Hyde, Simon Claridge, Jaswinder Gill, Julian Bostock, Manav Sohal, Bradley Porter, Mark O'Neill, Reza Razavi, Steve Niederer, Christopher Aldo Rinaldi
OBJECTIVES: The purpose of this study was to identify the optimal pacing site for the left ventricular (LV) lead in ischemic patients with poor response to cardiac resynchronization therapy (CRT). BACKGROUND: LV endocardial pacing may offer benefit over conventional CRT in ischemic patients. METHODS: We performed cardiac magnetic resonance, invasive electroanatomic mapping (EAM), and measured the acute hemodynamic response (AHR) in patients with existing CRT systems...
December 2016: JACC. Clinical Electrophysiology
https://www.readbyqxmd.com/read/28058479/electrocardiographic-rr-and-qt-interval-variability-in-patients-with-atrial-septal-defect-and-healthy-children
#9
Yoshihiko Eryu, Tadayoshi Hata, Arisa Nagatani, Yuri Funamoto, Hidetoshi Uchida, Masayuki Fujino, Hiroko Boda, Masafumi Miyata, Tetsushi Yoshikawa
Atrial septal defect is a common congenital heart disease. In patients with atrial septal defect, left-to-right shunting increases the right atrial and right ventricular preload. This pathological change affects sinus node automaticity and myocardial depolarization and repolarization, and has the potential to evoke arrhythmogenic substrates. We examined the effect of atrial septal defect on sinus node automaticity and myocardial repolarization by investigating the variability in the repolarization interval, namely the QT variability index (QTVI) and variability ratio (VR)...
January 5, 2017: Pediatric Cardiology
https://www.readbyqxmd.com/read/28056022/l-type-calcium-channel-inhibition-contributes-to-the-proarrhythmic-effects-of-aconitine-in-human-cardiomyocytes
#10
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/28049836/stochastic-initiation-and-termination-of-calcium-mediated-triggered-activity-in-cardiac-myocytes
#11
Zhen Song, Zhilin Qu, Alain Karma
Cardiac myocytes normally initiate action potentials in response to a current stimulus that depolarizes the membrane above an excitation threshold. Aberrant excitation can also occur due to spontaneous calcium (Ca(2+)) release (SCR) from intracellular stores after the end of a preceding action potential. SCR drives the Na(+)/Ca(2+) exchange current inducing a "delayed afterdepolarization" that can in turn trigger an action potential if the excitation threshold is reached. This "triggered activity" is known to cause arrhythmias, but how it is initiated and terminated is not understood...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28011703/optogenetic-termination-of-ventricular-arrhythmias-in-the-whole-heart-towards-biological-cardiac-rhythm-management
#12
Emile C A Nyns, Annemarie Kip, Cindy I Bart, Jaap J Plomp, Katja Zeppenfeld, Martin J Schalij, Antoine A F de Vries, Daniël A Pijnappels
AIMS: Current treatments of ventricular arrhythmias rely on modulation of cardiac electrical function through drugs, ablation or electroshocks, which are all non-biological and rather unspecific, irreversible or traumatizing interventions. Optogenetics, however, is a novel, biological technique allowing electrical modulation in a specific, reversible and trauma-free manner using light-gated ion channels. The aim of our study was to investigate optogenetic termination of ventricular arrhythmias in the whole heart...
December 23, 2016: European Heart Journal
https://www.readbyqxmd.com/read/27930354/simultaneous-non-invasive-epicardial-and-endocardial-mapping-in-patients-with-brugada-syndrome-new-insights-into-arrhythmia-mechanisms
#13
Boris Rudic, Maria Chaykovskaya, Alexey Tsyganov, Vitaly Kalinin, Erol Tülümen, Theano Papavassiliu, Christina Dösch, Volker Liebe, Jürgen Kuschyk, Susanne Röger, Ibrahim El-Battrawy, Ibrahim Akin, Marina Yakovleva, Elena Zaklyazminskaya, Anna Shestak, Stanislav Kim, Mikhail Chmelevsky, Martin Borggrefe
BACKGROUND: The underlying mechanisms of Brugada syndrome (BrS) are not completely understood. Recent studies provided evidence that the electrophysiological substrate, leading to electrocardiogram abnormalities and/or ventricular arrhythmias, is located in the right ventricular outflow tract (RVOT). The purpose of this study was to examine abnormalities of epicardial and endocardial local unipolar electrograms by simultaneous noninvasive mapping in patients with BrS. METHODS AND RESULTS: Local epicardial and endocardial unipolar electrograms were analyzed using a novel noninvasive epi- and endocardial electrophysiology system (NEEES) in 12 patients with BrS and 6 with right bundle branch block for comparison...
November 14, 2016: Journal of the American Heart Association
https://www.readbyqxmd.com/read/27926871/in%C3%A2-vivo-visualization-of-cardiomyocyte-apicobasal-polarity-reveals-epithelial-to-mesenchymal-like-transition-during-cardiac-trabeculation
#14
Vanesa Jiménez-Amilburu, S Javad Rasouli, David W Staudt, Hiroyuki Nakajima, Ayano Chiba, Naoki Mochizuki, Didier Y R Stainier
Despite great strides in understanding cardiac trabeculation, many mechanistic aspects remain unclear. To elucidate how cardiomyocyte shape changes are regulated during this process, we engineered transgenes to label their apical and basolateral membranes. Using these tools, we observed that compact-layer cardiomyocytes are clearly polarized while delaminating cardiomyocytes have lost their polarity. The apical transgene also enabled the imaging of cardiomyocyte apical constriction in real time. Furthermore, we found that Neuregulin signaling and blood flow/cardiac contractility are required for cardiomyocyte apical constriction and depolarization...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27926853/a-dynamical-threshold-for-cardiac-delayed-afterdepolarization-mediated-triggered-activity
#15
Michael B Liu, Christopher Y Ko, Zhen Song, Alan Garfinkel, James N Weiss, Zhilin Qu
Ventricular myocytes are excitable cells whose voltage threshold for action potential (AP) excitation is ∼-60 mV at which INa is activated to give rise to a fast upstroke. Therefore, for a short stimulus pulse to elicit an AP, a stronger stimulus is needed if the resting potential lies further away from the INa threshold, such as in hypokalemia. However, for an AP elicited by a long duration stimulus or a diastolic spontaneous calcium release, we observed that the stimulus needed was lower in hypokalemia than in normokalemia in both computer simulations and experiments of rabbit ventricular myocytes...
December 6, 2016: Biophysical Journal
https://www.readbyqxmd.com/read/27923791/reduced-density-and-altered-regulation-of-rat-atrial-l-type-ca2-current-in-rat-heart-failure
#16
Richard C Bond, Simon M Bryant, Judy J Watson, Jules C Hancox, Clive H Orchard, Andrew F James
Atrial L-type Ca(2+) current (ICaL) downregulation in heart failure contributes to the pathogenesis of atrial fibrillation and is proposed to involve reduction in channel phosphorylation by PKA. The regulation of atrial ICaL was examined in heart failure. Anesthetized adult male Wistar rats underwent surgical coronary artery ligation (CAL, N=10) or equivalent sham-operation (Sham, N=12). Left atrial myocytes were isolated ~18 weeks post-surgery and whole-cell currents recorded (holding potential=-80 mV). ICaL activated by depolarizing pulses to voltages from -40 to +50 mV were normalized to cell capacitance and current density-voltage relations plotted...
December 6, 2016: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/27878490/cardiac-body-surface-potentials-in-rats-with-experimental-pulmonary-hypertension-during-ventricular-depolarization
#17
O V Suslonova, S L Smirnova, I M Roshchevskaya
The spatial and the amplitude-temporal parameters of cardiac body surface potentials were examined in female Wistar rats with experimental pulmonary hypertension during ventricular depolarization. The cardiac body surface potentials have been led from 64 subcutaneous electrodes evenly distributed across the chest surface prior to and 4 weeks after subcutaneous injection of a single dose of monocrotaline (60 mg/kg). Right ventricular hypertrophy and electrophysiological remodeling of the heart developed in rats with experimental pulmonary hypertension in 4 weeks after monocrotaline injection; these changes led to a significant increase in amplitude and temporal characteristics of the cardioelectric field on the body surface in comparison with the initial state...
November 2016: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/27833567/myofibroblasts-electrotonically-coupled-to-cardiomyocytes-alter-conduction-insights-at-the-cellular-level-from-a-detailed-in-silico-tissue-structure-model
#18
Florian Jousset, Ange Maguy, Stephan Rohr, Jan P Kucera
Fibrotic myocardial remodeling is typically accompanied by the appearance of myofibroblasts (MFBs). In vitro, MFBs were shown to slow conduction and precipitate ectopic activity following gap junctional coupling to cardiomyocytes (CMCs). To gain further mechanistic insights into this arrhythmogenic MFB-CMC crosstalk, we performed numerical simulations in cell-based high-resolution two-dimensional tissue models that replicated experimental conditions. Cell dimensions were determined using confocal microscopy of single and co-cultured neonatal rat ventricular CMCs and MFBs...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27815365/xanthohumol-modulates-calcium-signaling-in-rat-ventricular-myocytes-possible-antiarrhythmic-properties
#19
Juan Jose Arnaiz-Cot, Lars Cleemann, Martin Morad
Cardiac arrhythmia is a major cause of mortality in cardiovascular pathologies. A host of drugs targeted to sarcolemmal Na(+), Ca(2+), and K(+) channels has had limited success clinically. Recently, Ca(2+) signaling has been target of pharmacotherapy based on finding that leaky ryanodine receptors elevate local Ca(2+) concentrations causing membrane depolarizations that trigger arrhythmias. In this study, we report that xanthohumol, an antioxidant extracted from hops showing therapeutic effects in other pathologies, suppresses aberrant ryanodine receptor Ca(2+) release...
January 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27815173/stable-gastric-pentadecapeptide-bpc-157-and-bupivacaine
#20
Gordana Zivanovic-Posilovic, Diana Balenovic, Ivan Barisic, Dean Strinic, Vasilije Stambolija, Mario Udovicic, Sandra Uzun, Domagoj Drmic, Josipa Vlainic, Martina Lovric Bencic, Aleksandra Sindic, Sven Seiwerth, Predrag Sikiric
Bupivacaine toxicity following accidental overdose still lacks therapeutic solution. However, there are major arguments for testing BPC 157 against bupivacaine toxicity in vivo in rats, in particular, and then finally, in vitro. These are: the lack of any known BPC 157 toxicity, a lifesaving effect via the mitigation of arrhythmias in rats underwent hyperkalemia or digitalis toxicity, the elimination of hyperkalemia and arrhythmias in rats underwent succinylcholine toxicity and finally, the reduction of potassium-induced depolarization in vitro (in HEK293 cells) in severe hyperkalemia...
December 15, 2016: European Journal of Pharmacology
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