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APD alternans

Matthew Kennedy, Donald M Bers, Nipavan Chiamvimonvat, Daisuke Sato
KEY POINTS: A mathematical model of a small conductance Ca(2)(+) -activated potassium (SK) channel was developed and incorporated into a physiologically detailed ventricular myocyte model. Ca(2+) -sensitive K(+) currents promote negative intracellular Ca(2+) to membrane voltage (CAi(2+) → Vm ) coupling. Increase of Ca(2+) -sensitive K(+) currents can be responsible for electromechanically discordant alternans and quasiperiodic oscillations at the cellular level. At the tissue level, Turing-type instability can occur when Ca(2+) -sensitive K(+) currents are increased...
November 30, 2016: Journal of Physiology
Xiaowei Zhong, Bo Sun, Alexander Vallmitjana, Tao Mi, Wenting Guo, Mingke Ni, Ruiwu Wang, Ang Guo, Henry J Duff, Anne M Gillis, Long-Sheng Song, Leif Hove-Madsen, Raul Benitez, S R Wayne Wayne Chen
Beat-to-beat alternations in the amplitude of the cytosolic Ca(2+) transient (Ca(2+) alternans) are thought to be the primary cause of cardiac alternans that can lead to cardiac arrhythmias and sudden death. Despite its important role in arrhythmogenesis, the mechanism underlying Ca(2+) alternans remains poorly understood. Here we investigated the role of cardiac ryanodine receptor (RyR2), the major Ca(2+) release channel responsible for cytosolic Ca(2+) transients, in cardiac alternans. Using a unique mouse model harboring a suppression-of-function (SOF) RyR2 mutation (E4872Q), we assessed the effect of genetically suppressing RyR2 function on Ca(2+) and action potential duration (APD) alternans in intact hearts, and electrocardiogram (ECG) alternans in vivo...
August 31, 2016: Biochemical Journal
Seth H Weinberg
Cardiac electrical dynamics are governed by cellular-level properties, such as action potential duration (APD) restitution and intracellular calcium (Ca) handling, and tissue-level properties, including conduction velocity restitution and cell-cell coupling. Irregular dynamics at the cellular level can lead to instabilities in cardiac tissue, including alternans, a beat-to-beat alternation in the action potential and/or the intracellular Ca transient. In this study, we incorporate a detailed single cell coupled map model of Ca cycling and bidirectional APD-Ca coupling into a spatially extended tissue model to investigate the influence of sarcoplasmic reticulum (SR) Ca uptake and release properties on alternans and conduction block...
2016: Clinical Medicine Insights. Cardiology
Nele Vandersickel, Arne Defauw, Peter Dawyndt, Alexander V Panfilov
The main mechanism of formation of reentrant cardiac arrhythmias is via formation of waveblocks at heterogeneities of cardiac tissue. We report that heterogeneity and the area of waveblock can extend itself in space and can result formation of new additional sources, or termination of existing sources of arrhythmias. This effect is based on a new form of instability, which we coin as global alternans instability (GAI). GAI is closely related to the so-called (discordant) alternans instability, however its onset is determined by the global properties of the APD-restitution curve and not by its slope...
2016: Scientific Reports
Y Huang, D-N Wang, P Liu, Y Song, H-M Cui, J-Y Zhang, J Blackwell, D-N Liao
OBJECTIVE: To observe the effects of local radiofrequency denervation on ventricular effective refractory periods, electrical alternans and ventricular arrhythmia susceptibility post myocardial infarction. MATERIALS AND METHODS: Thirty-four mongrel dogs were randomly divided into the normal heart group (n = 16, 8 in sham and 8 in local sympathetic denervation - LSD) and the acute myocardial ischemia (AMI) group (n = 18, 9 in control and 9 in LSD). The left cardiac sympathetic nerve was denervated with irrigated catheter radiofrequency ablation...
June 2016: European Review for Medical and Pharmacological Sciences
Aditya V S Ponnaluri, Luigi E Perotti, Michael Liu, Zhilin Qu, James N Weiss, Daniel B Ennis, William S Klug, Alan Garfinkel
Heart failure is a leading cause of death, yet its underlying electrophysiological (EP) mechanisms are not well understood. In this study, we use a multiscale approach to analyze a model of heart failure and connect its results to features of the electrocardiogram (ECG). The heart failure model is derived by modifying a previously validated electrophysiology model for a healthy rabbit heart. Specifically, in accordance with the heart failure literature, we modified the cell EP by changing both membrane currents and calcium handling...
June 2016: PLoS Computational Biology
Justin Eastman, Julian Sass, Johnny M Gomes, Rodrigo Weber Dos Santos, Elizabeth M Cherry
Cardiac electrical alternans is a period-2 dynamical behavior with alternating long and short action potential durations (APD) that often precedes dangerous arrhythmias associated with cardiac arrest. Despite the importance of alternans, many current ordinary differential equations models of cardiac electrophysiology do not produce alternans, thereby limiting the use of these models for studying the mechanisms that underlie this condition. Because delay differential equations (DDEs) commonly induce complex dynamics in other biological systems, we investigate whether incorporating DDEs can lead to alternans development in cardiac models by studying the Fox et al...
September 7, 2016: Journal of Theoretical Biology
Gary Tse, Sheung Ting Wong, Vivian Tse, Jie Ming Yeo
Action potential duration (APD) and conduction velocity restitution explain the dependence of these parameters on the previous diastolic interval (DI). It is considered to be an adaptive mechanism for preserving diastole at fast heart rates. Hypokalaemia is known to induce ventricular arrhythmias that could be prevented by heptanol, the gap junction uncoupler, mediated through increases in ventricular refractory period (VERP) without alterations in APDs. The present study investigated alternans and restitution properties during normokalaemia, hypokalaemia alone or hypokalaemia with heptanol (0...
June 2016: Biomedical Reports
J D Bayer, G G Lalani, E J Vigmond, S M Narayan, N A Trayanova
BACKGROUND: Mechanisms of ventricular tachycardia (VT) and ventricular fibrillation (VF) in patients with heart failure (HF) are undefined. OBJECTIVE: The purpose of this study was to elucidate VT/VF mechanisms in HF by using a computational-clinical approach. METHODS: In 53 patients with HF and 18 control patients, we established the relationship between low-amplitude action potential voltage alternans (APV-ALT) during ventricular pacing at near-resting heart rates and VT/VF on long-term follow-up...
September 2016: Heart Rhythm: the Official Journal of the Heart Rhythm Society
Rupamanjari Majumder, Marc C Engels, Antoine A F de Vries, Alexander V Panfilov, Daniël A Pijnappels
Fibrosis and altered gap junctional coupling are key features of ventricular remodelling and are associated with abnormal electrical impulse generation and propagation. Such abnormalities predispose to reentrant electrical activity in the heart. In the absence of tissue heterogeneity, high-frequency impulse generation can also induce dynamic electrical instabilities leading to reentrant arrhythmias. However, because of the complexity and stochastic nature of such arrhythmias, the combined effects of tissue heterogeneity and dynamical instabilities in these arrhythmias have not been explored in detail...
2016: Scientific Reports
Wei-Chung Tsai, Yi-Hsin Chan, Chia-Hsiang Hsueh, Thomas H Everett, Po-Cheng Chang, Eue-Keun Choi, Michael A Olaopa, Shien-Fong Lin, Changyu Shen, Maria Aleksandra Kudela, Michael Rubart-von der Lohe, Zhenhui Chen, Pooja Jadiya, Dhanendra Tomar, Emily Luvison, Nicholas Anzalone, Vickas V Patel, Peng-Sheng Chen
BACKGROUND: The melanin synthesis enzyme dopachrome tautomerase (Dct) regulates intracellular Ca(2+) in melanocytes. Homozygous Dct knockout (Dct(-/-)) adult mice are vulnerable to atrial arrhythmias (AA). OBJECTIVE: The purpose of this study was to determine whether apamin-sensitive small conductance Ca(2+)-activated K(+) (SK) currents are upregulated in Dct(-/-) mice and contribute to AA. METHODS: Optical mapping was used to study the membrane potential of the right atrium in Langendorff perfused Dct(-/-) (n = 9) and Dct(+/-) (n = 9) mice...
July 2016: Heart Rhythm: the Official Journal of the Heart Rhythm Society
Amr Al Abed, Nigel H Lovell, Socrates Dokos
INTRODUCTION: This study aims to characterize the regional variability in rate-adaptation in the atria. METHODS AND RESULTS: Action potential (AP) responses to pulses with uniform as well as pseudo-random non-uniform pacing intervals were recorded from rabbit sino-atrial node, right and left atrial pectinate as well as pulmonary vein antrum tissue preparations using conventional intracellular glass microelectrodes. Steady-state restitution curves were reconstructed for various AP waveform metrics...
June 2016: Journal of Cardiovascular Electrophysiology
Dandan Wang, Tao Liu, Shaobo Shi, Ran Li, Yingguang Shan, Yan Huang, Dan Hu, Congxin Huang
Catestatin (CST), which is emerging as a novel cardiac modulator, can protect the heart against excessive sympathetic drive in hypertensive cardiomyopathy. The aim of this study is to investigate whether exogenous CST decreases excessive cardiac sympathetic drive and improves autonomic function and exerts cardioprotective effects in myocardial infarction (MI) rats. Rats were divided into a sham group, MI group, and MI plus CST (MI + CST) group. Four weeks later, the autonomic function of the animals was assessed by analyzing heart rate variability (HRV) and measuring plasma catecholamine...
January 27, 2016: Journal of Cardiovascular Pharmacology and Therapeutics
Kanchan Kulkarni, Elena G Tolkacheva
Cardiac restitution is the shortening of the action potential duration with an increase in the heart rate. A shorter action potential duration enables a longer diastolic interval which ensures that the heart gets adequate time to refill with blood. At higher rates however, restitution becomes steep and thus, can lead to unstable electrical activity (alternans) in the heart, leading to fatal cardiac rhythms. It has been proposed that maintaining a shallow slope of cardiac restitution could have potentially anti-arrhythmic effects...
2015: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
Shuenn-Nan Chiu, Chia-Ti Tsai, Lian-Yu Lin, Shu-Chien Huang, Yih-Sharng Chen, Jou-Kou Wang, Mei-Hwan Wu, Ling-Ping Lai, Jiunn-Lee Lin
BACKGROUND: Ventricular arrhythmia is an important cause of late death in patients with repaired tetralogy of Fallot (rTOF). By using an rTOF canine model, we investigated the role of repolarization alternans and its electrophysiological mechanisms. METHODS AND RESULTS: Six dogs received right ventricular outflow tract (RVOT) transannular patch, pulmonary valve destruction, and right bundle branch ablation to simulate rTOF. After 1 year, we performed high-resolution dual-voltage and calcium optical mapping to record action potentials and calcium transients on the excised right ventricular outflow tract wedges...
December 2015: Journal of the American Heart Association
James Winter, Michael J Shattock
The rate of repolarization (RRepol) and so the duration of the cardiac action potential are determined by the balance of inward and outward currents across the cardiac membrane (net ionic current). Plotting action potential duration (APD) as a function of the RRepol reveals an inverse non-linear relationship, arising from the geometric association between these two factors. From the RRepol-APD relationship, it can be observed that a longer action potential will exhibit a greater propensity to shorten, or prolong, for a given change in the RRepol (i...
March 2016: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
Yann Prudat, Roshni V Madhvani, Marina Angelini, Nils P Borgstom, Alan Garfinkel, Hrayr S Karagueuzian, James N Weiss, Enno de Lange, Riccardo Olcese, Jan P Kucera
KEY POINTS: Beat-to-beat alternation (alternans) of the cardiac action potential duration is known to precipitate life-threatening arrhythmias and can be driven by the kinetics of voltage-gated membrane currents or by instabilities in intracellular calcium fluxes. To prevent alternans and associated arrhythmias, suitable markers must be developed to quantify the susceptibility to alternans; previous theoretical studies showed that the eigenvalue of the alternating eigenmode represents an ideal marker of alternans...
May 1, 2016: Journal of Physiology
Seth H Weinberg
Alternans, a beat-to-beat alternation in the cardiac action potential duration (APD), is a dynamical instability linked with the initiation of arrhythmias and sudden cardiac death, and arises via a period-doubling bifurcation when myocytes are stimulated at fast rates. In this study, we analyze the stability of a propagating electrical wave in a one-dimensional cardiac myocyte model in response to an arrhythmogenic rhythm known as alternate pacing. Using a discrete-time kinematic model and complex frequency (Z) domain analysis, we derive analytical expressions to predict phase reversals and spatial discordance in the interbeat interval (IBI) and APD, which, importantly, cannot be predicted with a model that neglects the influence of cell coupling on repolarization...
October 2015: Chaos
Bing Huang, Lilei Yu, Bo He, Songyun Wang, Zhibing Lu, Kai Liao, Zhuo Wang, Xiaoya Zhou, Wenbo He, Hong Jiang
AIMS: We aimed to investigate whether sympathetic denervation of the heart and kidney had similar effects on ventricular effective refractory period (ERP) and action potential duration (APD) restitution properties in a canine model. METHODS AND RESULTS: Twenty-four anaesthetised open-chest dogs (17-20 kg) were assigned to a sham operation group (n=8), a cardiac sympathetic denervation group (CSD, n=8) or a renal sympathetic denervation group (RSD, n=8). CSD was performed by ablating the caudal half of the LSG and T2-T4 thoracic sympathetic ganglia, while RSD was performed by ablating four sites on the adventitial surface of each renal artery...
September 2015: EuroIntervention
Yi-Hsin Chan, Wei-Chung Tsai, Jum-Suk Ko, Dechun Yin, Po-Cheng Chang, Michael Rubart, James N Weiss, Thomas H Everett, Shien-Fong Lin, Peng-Sheng Chen
BACKGROUND: Hypokalemia increases the vulnerability to ventricular fibrillation. We hypothesize that the apamin-sensitive small-conductance calcium-activated potassium current (IKAS) is activated during hypokalemia and that IKAS blockade is proarrhythmic. METHODS AND RESULTS: Optical mapping was performed in 23 Langendorff-perfused rabbit ventricles with atrioventricular block and either right or left ventricular pacing during normokalemia or hypokalemia. Apamin prolonged the action potential duration (APD) measured to 80% repolarization (APD80) by 26 milliseconds (95% confidence interval [CI], 14-37) during normokalemia and by 54 milliseconds (95% CI, 40-68) during hypokalemia (P=0...
October 13, 2015: Circulation
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