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APD alternans

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https://www.readbyqxmd.com/read/29753687/istaroxime-a-positive-inotropic-agent-devoid-of-proarrhythmic-properties-in-sensitive-chronic-atrioventricular-block-dogs
#1
Alexandre Bossu, Amée Kostense, Henriette D M Beekman, Marien J C Houtman, Marcel A G van der Heyden, Marc A Vos
Current inotropic agents in heart failure therapy associate with low benefit and significant adverse effects, including ventricular arrhythmias. Istaroxime, a novel Na+ /K+ -transporting ATPase inhibitor, also stimulates SERCA2a activity, which would confer improved inotropic and lusitropic properties with less proarrhythmic effects. We investigated hemodynamic, electrophysiological and potential proarrhythmic and antiarrhythmic effects of istaroxime in control and chronic atrioventricular block (CAVB) dogs sensitive to drug-induced Torsades de Pointes arrhythmias (TdP)...
May 10, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29621066/electrical-stimulation-based-renal-nerve-mapping-exacerbates-ventricular-arrhythmias-during-acute-myocardial-ischaemia
#2
Bing Huang, Xiaoya Zhou, Menglong Wang, Xuefei Li, Liping Zhou, Guannan Meng, Yuhong Wang, Zhuo Wang, Songyun Wang, Lilei Yu, Hong Jiang
OBJECTIVE: Blood pressure elevation in response to transient renal nerve stimulation (RNS) has been used to determine the ablation target and endpoint of renal denervation. This study aimed to evaluate the safety of transient RNS in canines with normal or ischaemic hearts. METHODS: In ten normal (Group 1) and six healed myocardial infarction (HMI) (Group 2) canines, a large-tip catheter was inserted into the left or right renal artery to perform transient RNS. The left stellate ganglion neural activity (LSGNA) and ventricular electrophysiological parameters were measured at baseline and during transient RNS...
April 4, 2018: Journal of Hypertension
https://www.readbyqxmd.com/read/29410631/sympathetic-nervous-regulation-of-calcium-and-action-potential-alternans-in-the-intact-heart
#3
James Winter, Martin J Bishop, Catherine D E Wilder, Christopher O'Shea, Davor Pavlovic, Michael J Shattock
Rationale: Arrhythmogenic cardiac alternans are thought to be an important determinant for the initiation of ventricular fibrillation. There is limited information on the effects of sympathetic nerve stimulation (SNS) on alternans in the intact heart and the conclusions of existing studies, focused on investigating electrical alternans, are conflicted. Meanwhile, several lines of evidence implicate instabilities in Ca handling, not electrical restitution, as the primary mechanism underpinning alternans. Despite this, there have been no studies on Ca alternans and SNS in the intact heart...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29377142/mechanisms-linking-t-wave-alternans-to-spontaneous-initiation-of-ventricular-arrhythmias-in-rabbit-models-of-long-qt-syndrome
#4
Weiqing Liu, Tae Yun Kim, Xiaodong Huang, Michael B Liu, Gideon Koren, Bum-Rak Choi, Zhilin Qu
KEY POINTS: T-wave alternans (TWA) and T-wave lability (TWL) are precursors of ventricular arrhythmias in long QT syndrome; however, the mechanistic link remains to be clarified. Computer simulations show that action potential duration (APD) prolongation and slowed heart rates promote APD alternans and chaos, manifesting as TWA and TWL, respectively. Regional APD alternans and chaos can exacerbate pre-existing or induce de novo APD dispersion, which combines with enhanced ICa,L to result in premature ventricular complexes (PVCs) originating from the APD gradient region...
April 15, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29356998/real-time-closed-loop-diastolic-interval-control-prevents-cardiac-alternans-in-isolated-whole-rabbit-hearts
#5
Kanchan Kulkarni, Steven W Lee, Ryan Kluck, Elena G Tolkacheva
Cardiac alternans, a beat-to-beat alternation in action potential duration (APD), can lead to fatal arrhythmias. During periodic pacing, changes in diastolic interval (DI) depend on subsequent changes in APD, thus enhancing cardiac instabilities through a 'feedback' mechanism. Recently, an anti-arrhythmic Constant DI pacing protocol was proposed and shown to be effective in suppressing alternans in 0D and 1D in silico studies. However, previous experimental validation of Constant DI pacing in the heart has been unsuccessful due to the spatio-temporal complexity of 2D cardiac tissue and the technical challenges in its real-time implementation...
April 2018: Annals of Biomedical Engineering
https://www.readbyqxmd.com/read/29338006/a-model-for-cooperative-gating-of-l-type-ca2-channels-and-its-effects-on-cardiac-alternans-dynamics
#6
Daisuke Sato, Rose E Dixon, Luis F Santana, Manuel F Navedo
In ventricular myocytes, membrane depolarization during the action potential (AP) causes synchronous activation of multiple L-type CaV1.2 channels (LTCCs), which trigger the release of calcium (Ca2+) from the sarcoplasmic reticulum (SR). This results in an increase in intracellular Ca2+ (Cai) that initiates contraction. During pulsus alternans, cardiac contraction is unstable, going from weak to strong in successive beats despite a constant heart rate. These cardiac alternans can be caused by the instability of membrane potential (Vm) due to steep AP duration (APD) restitution (Vm-driven alternans), instability of Cai cycling (Ca2+-driven alternans), or both, and may be modulated by functional coupling between clustered CaV1...
January 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29337261/heart-rate-variability-alters-cardiac-repolarization-and-electromechanical-dynamics
#7
Vrishti M Phadumdeo, Seth H Weinberg
Heart rate continuously varies due to autonomic regulation, stochasticity in pacemaking, and circadian rhythm, collectively termed heart rate variability (HRV), during normal physiological conditions. Low HRV is clinically associated with an elevated risk of cardiac arrhythmias. Alternans, a beat-to-beat alternation in action potential duration (APD) and/or intracellular calcium (Ca) transient, is a well-known risk factor associated with cardiac arrhythmias that is typically studied under conditions of a constant pacing rate, i...
April 7, 2018: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/29104543/simultaneous-quantification-of-spatially-discordant-alternans-in-voltage-and-intracellular-calcium-in-langendorff-perfused-rabbit-hearts-and-inconsistencies-with-models-of-cardiac-action-potentials-and-ca-transients
#8
Ilija Uzelac, Yanyan C Ji, Daniel Hornung, Johannes Schröder-Scheteling, Stefan Luther, Richard A Gray, Elizabeth M Cherry, Flavio H Fenton
Rationale: Discordant alternans, a phenomenon in which the action potential duration (APDs) and/or intracellular calcium transient durations (CaDs) in different spatial regions of cardiac tissue are out of phase, present a dynamical instability for complex spatial dispersion that can be associated with long-QT syndrome (LQTS) and the initiation of reentrant arrhythmias. Because the use of numerical simulations to investigate arrhythmic effects, such as acquired LQTS by drugs is beginning to be studied by the FDA, it is crucial to validate mathematical models that may be used during this process...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29073179/restitution-characteristics-of-his-bundle-and-working-myocardium-in-isolated-rabbit-hearts
#9
Shangwei Huang, Liqun Wu, Jian Huang, Nuttanont Panitchob, Nan Hu, Ravi Ranjan, Derek J Dosdall
The Purkinje system (PS) and the His bundle have been recently implicated as an important driver of the rapid activation rate after 1-2 minutes of ventricular fibrillation (VF). It is unknown whether activations during VF propagate through the His-Purkinje system to other portions of the the working myocardium (WM). Little is known about restitution characteristic differences between the His bundle and working myocardium at short cycle lengths. In this study, rabbit hearts (n = 9) were isolated, Langendorff-perfused, and electromechanically uncoupled with blebbistatin (10 μM)...
2017: PloS One
https://www.readbyqxmd.com/read/28989116/complex-restitution-behavior-and-reentry-in-a-cardiac-tissue-model-for-neonatal-mice
#10
Andreas Mayer, Philip Bittihn, Stefan Luther
Spatiotemporal dynamics in cardiac tissue emerging from the coupling of individual cardiomyocytes underlie the heart's normal rhythm as well as undesired and possibly life-threatening arrhythmias. While single cells and their transmembrane currents have been studied extensively, systematically investigating spatiotemporal dynamics is complicated by the nontrivial relationship between single-cell and emergent tissue properties. Mathematical models have been employed to bridge this gap and contribute to a deepened understanding of the onset, development, and termination of arrhythmias...
October 2017: Physiological Reports
https://www.readbyqxmd.com/read/28964159/distinguishing-mechanisms-for-alternans-in-cardiac-cells-using-constant-diastolic-interval-pacing
#11
Elizabeth M Cherry
Alternans, a proarrhythmic dynamical state in which cardiac action potentials alternate between long and short durations despite a constant pacing period, traditionally has been explained at the cellular level using nonlinear dynamics principles under the assumption that the action potential duration (APD) is determined solely by the time elapsed since the end of the previous action potential, called the diastolic interval (DI). In this scenario, APDs at a steady state should be the same provided that the preceding DIs are the same...
September 2017: Chaos
https://www.readbyqxmd.com/read/28964144/constant-di-pacing-suppresses-cardiac-alternans-formation-in-numerical-cable-models
#12
S Zlochiver, C Johnson, E G Tolkacheva
Cardiac repolarization alternans describe the sequential alternation of the action potential duration (APD) and can develop during rapid pacing. In the ventricles, such alternans may rapidly turn into life risking arrhythmias under conditions of spatial heterogeneity. Thus, suppression of alternans by artificial pacing protocols, or alternans control, has been the subject of numerous theoretical, numerical, and experimental studies. Yet, previous attempts that were inspired by chaos control theories were successful only for a short spatial extent (<2 cm) from the pacing electrode...
September 2017: Chaos
https://www.readbyqxmd.com/read/28964143/memory-in-a-fractional-order-cardiomyocyte-model-alters-properties-of-alternans-and-spontaneous-activity
#13
T Comlekoglu, S H Weinberg
Cardiac memory is the dependence of electrical activity on the prior history of one or more system state variables, including transmembrane potential (Vm), ionic current gating, and ion concentrations. While prior work has represented memory either phenomenologically or with biophysical detail, in this study, we consider an intermediate approach of a minimal three-variable cardiomyocyte model, modified with fractional-order dynamics, i.e., a differential equation of order between 0 and 1, to account for history-dependence...
September 2017: Chaos
https://www.readbyqxmd.com/read/28964128/theory-of-the-development-of-alternans-in-the-heart-during-controlled-diastolic-interval-pacing
#14
Niels F Otani
The beat-to-beat alternation in action potential durations (APDs) in the heart, called APD alternans, has been linked to the development of serious cardiac rhythm disorders, including ventricular tachycardia and fibrillation. The length of the period between action potentials, called the diastolic interval (DI), is a key dynamical variable in the standard theory of alternans development. Thus, methods that control the DI may be useful in preventing dangerous cardiac rhythms. In this study, we examine the dynamics of alternans during controlled-DI pacing using a series of single-cell and one-dimensional (1D) fiber models of alternans dynamics...
September 2017: Chaos
https://www.readbyqxmd.com/read/28894423/%C3%AE-adrenergic-inhibition-prevents-action-potential-and-calcium-handling-changes-during-regional-myocardial-ischemia
#15
Shannon R Murphy, Lianguo Wang, Zhen Wang, Philip Domondon, Di Lang, Beth A Habecker, Rachel C Myles, Crystal M Ripplinger
β-adrenergic receptor (β-AR) blockers may be administered during acute myocardial infarction (MI), as they reduce energy demand through negative chronotropic and inotropic effects and prevent ischemia-induced arrhythmogenesis. However, the direct effects of β-AR blockers on ventricular electrophysiology and intracellular Ca(2+) handling during ischemia remain unknown. Using optical mapping of transmembrane potential (with RH237) and sarcoplasmic reticulum (SR) Ca(2+) (with the low-affinity indicator Fluo-5N AM), the effects of 15 min of regional ischemia were assessed in isolated rabbit hearts (n = 19)...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28842915/roles-of-impaired-intracellular-calcium-cycling-in-arrhythmogenicity-of-diabetic-mouse-model
#16
Chung-Chuan Chou, Chien-Te Ho, Hui-Ling Lee, Yen Chu, Tzung-Hai Yen, Ming-Shien Wen, Shien-Fong Lin, Cheng-Hung Lee, Po-Cheng Chang
BACKGROUND: Diabetes mellitus is associated an increased risk of ventricular arrhythmias (VAs), but the underlying electrophysiological mechanisms are not fully explored. This study was aimed to test whether dynamic factors and Cai handling play roles in arrhythmogenesis of a diabetic animal model. METHODS: We used 26 db/db type 2 diabetes mice and 28 control mice in this study. VA inducibility was evaluated in vivo under isoflurane general anesthesia. The intracellular Ca(2+) (Cai ) and membrane voltage (Vm ) signals of the Langendorff-perfused mouse hearts were simultaneously recorded using the optical mapping technique...
August 26, 2017: Pacing and Clinical Electrophysiology: PACE
https://www.readbyqxmd.com/read/28821956/effects-of-ageing-on-pro-arrhythmic-ventricular-phenotypes-in-incrementally-paced-murine-pgc-1%C3%AE-hearts
#17
Shiraz Ahmad, Haseeb Valli, Charlotte E Edling, Andrew A Grace, Kamalan Jeevaratnam, Christopher L-H Huang
A range of chronic clinical conditions accompany cardiomyocyte energetic dysfunction and constitute independent risk factors for cardiac arrhythmia. We investigated pro-arrhythmic and arrhythmic phenotypes in energetically deficient C57BL mice with genetic ablation of the mitochondrial promoter peroxisome proliferator-activated receptor-γ coactivator-1β (Pgc-1β), a known model of ventricular arrhythmia. Pro-arrhythmic and cellular action potential (AP) characteristics were compared in intact Langendorff-perfused hearts from young (12-16 week) and aged (> 52 week), wild-type (WT) and Pgc-1β-/- mice...
December 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28662005/camkii-activation-promotes-cardiac-electrical-remodeling-and-increases-the-susceptibility-to-arrhythmia-induction-in-high-fat-diet-fed-mice-with-hyperlipidemia-conditions
#18
Peng Zhong, Dajun Quan, Yan Huang, He Huang
BACKGROUND: Obesity/hyperlipidemia is closely related to both atrial and ventricular arrhythmias. CaMKII, a multifunctional serine/threonine kinase, has been involved in cardiac arrhythmias of different etiologies. However, its role in obesity/hyperlipidemia-related cardiac arrhythmia is unexplored. The aim of this was to determine the involvement of CaMKII in the process. METHODS: Adult male APOE mice were fed a high-fat diet (HFD), administrated with KN93 (10 mg·kg·2d), a specific inhibitor of CaMKII...
October 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28290788/-the-myocardial-sleeves-of-the-pulmonary-veins-potential-implications-for-atrial-fibrillation
#19
Y V Egorov, L V Rozenshtrauh
Pulmonary veins (PVs) are thought to play an important role in the initiation of atrial fibrillation. However, systematic microelectrode studies from different regions of the left atria and PV myocardium remain limited. METHODS AND RESULTS: A 2-microelectrode technique was used to characterize electrophysiological properties of rat left atrial and PV myocardium, at baseline and during electrical stimulation. PV myocardium was characterized by prolonged action potential duration (APD) (74+/-2 ms in the PV mouth vs...
February 2017: Kardiologiia
https://www.readbyqxmd.com/read/28268303/effects-and-underlying-mechanisms-of-refractory-period-pacing-on-repolarization-dynamics-in-the-human-heart
#20
Diogo Santos, Michele Orini, Xin Zhou, Alfonso Bueno-Orovio, Ben Hanson, Peter Taggart, Martin Hayward, Blanca Rodriguez, Pier Lambiase
Repolarization alternans is related to the initiation of life threatening cardiac arrhythmias. Experimental and computational studies suggest that the abolishment of alternans using dynamic pacing protocols may prevent abnormal heart rhythms. In a recent animal study, refractory period pacing (RPP) on every other beat has shown promising results in alternans reduction. However, the cellular mechanisms underlying this therapy and its efficiency in human patients remain unclear. In this study, in vivo unipolar electrograms acquired during RPP from 240 epicardial sites from one patient were analysed...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
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