The Experts below are selected from a list of 273 Experts worldwide ranked by ideXlab platform
Luiz Belardinelli - One of the best experts on this subject based on the ideXlab platform.
-
late ina blocker gs967 supresses polymorphic ventricular tachycardia in a transgenic rabbit model of long qt type 2
Circulation-arrhythmia and Electrophysiology, 2020Co-Authors: Luiz Belardinelli, Jungmin Hwang, Tae Yun Kim, Dmitry Terentyev, Mingwang Zhong, Anatoli Y Kabakov, Peter Bronk, Karuppiah Arunachalam, Sridharan RajamaniAbstract:Background: Long QT syndrome has been associated with sudden cardiac death likely caused by early Afterdepolarizations (EADs) and polymorphic ventricular tachycardias (PVTs). Suppressing the late s...
-
an increase of late sodium current induces delayed Afterdepolarizations and sustained triggered activity in atrial myocytes
American Journal of Physiology-heart and Circulatory Physiology, 2008Co-Authors: Yejia Song, John C Shryock, Luiz BelardinelliAbstract:This study determined the role of a slowly inactivating component of sodium current (INa), late INa, to induce delayed Afterdepolarizations (DADs) and triggered activity. We hypothesized that an in...
-
ATP promotes development of Afterdepolarizations and triggered activity in cardiac myocytes.
American Journal of Physiology-Heart and Circulatory Physiology, 1994Co-Authors: Yejia Song, Luiz BelardinelliAbstract:The effect of extracellular ATP on transient inward current (Iti), delayed Afterdepolarization (DAD), early Afterdepolarization (EAD), and triggered activity were investigated in guinea pig isolated ventricular myocytes. ATP alone did not induce Afterdepolarizations nor did it significantly alter the resting membrane potentials and action potentials. However, when it was applied with drugs known to increase intracellular Ca2+, ATP facilitated the induction of Afterdepolarizations and triggered activity in approximately 60% of the cells. In the presence of isoproterenol, ATP increased the amplitude of Iti and DADs by 55 and 206%, respectively, and caused increases in the amplitude of L-type Ca2+ current (ICa) and EADs, which occasionally led to triggered activity. Similarly, addition of ATP increased the amplitude of Iti and DADs induced by elevated extracellular Ca2+ by 110 and 83%, respectively. Ryanodine inhibited the ATP-induced increase in Iti but not the increase in ICa. In the presence of BAY K 8644 or quinidine, ATP not only further prolonged the action potential durations by 18 +/- 4 and 17 +/- 4%, respectively, but also increased the amplitude of EADs. The present results show a novel arrhythmogenic effect of extracellular ATP, which facilitates the genesis of triggered arrhythmias when Ca2+ influx is increased, probably by further increasing Ca2+ influx from extracellular medium and Ca2+ release from intracellular stores.
-
Adenosine-sensitive Afterdepolarizations and triggered activity in guinea pig ventricular myocytes.
Circulation research, 1992Co-Authors: Yejia Song, S. Thedford, Bruce B. Lerman, Luiz BelardinelliAbstract:This study examines the cellular basis and specificity of the effects of adenosine on early Afterdepolarizations (EADs), delayed Afterdepolarizations (DADs), and triggered activity (TA) induced by various drugs with different mechanisms of action. Membrane potential and currents were measured in isolated guinea pig ventricular myocytes. Adenosine (10-100 microM) significantly (p less than 0.05) reduced the amplitude of DADs and suppressed TA induced by isoproterenol (10-50 nM) and forskolin (1 microM) but not those induced by dibutyryl cAMP (1 microM), ouabain (1-5 microM), and 7.2 mM [Ca2+]o. Adenosine also abolished EADs and TA induced by isoproterenol. In contrast, adenosine failed to abolish EADs and TA induced by quinidine (3 microM) or those that occurred spontaneously (i.e., in the absence of drugs). Transient inward current (ITi) was induced on repolarization after 2-second-long single depolarizing voltage steps or after 12-second-long trains of 300-msec depolarizing pulses. Concomitant with the attenuation of DADs, adenosine suppressed ITi caused by isoproterenol and forskolin but not those induced by ouabain, dibutyryl cAMP, and elevated [Ca2+]o. The amplitude of ITi was dependent on the magnitude of the activating voltage step, but the suppression of ITi by adenosine was not. The selective A1-adenosine receptor antagonist N-0861 (9-methyladenine derivative) antagonized the effects of adenosine on Afterdepolarizations, ITi, and TA. In myocytes from guinea pigs treated with pertussis toxin, adenosine failed to attenuate DADs and ITi or abolish TA induced by isoproterenol or forskolin. In parallel experiments, isoproterenol (10 nM) raised cellular cAMP from 5.7 +/- 0.2 to 8.1 +/- 0.1 pmol and the selective A1 receptor agonist cyclopentyladenosine (5 microM) reduced it to 6.5 +/- 0.2 pmol (p less than 0.05). Thus, adenosine specifically attenuates Afterdepolarizations and abolishes TA by suppressing ITiS that are associated with stimulation of adenylate cyclase via a pertussis toxin-sensitive A1 receptor-mediated action. In conclusion, the response of TA to adenosine may identify a mechanism of Afterdepolarization related to stimulation of adenylate cyclase.
Yejia Song - One of the best experts on this subject based on the ideXlab platform.
-
an increase of late sodium current induces delayed Afterdepolarizations and sustained triggered activity in atrial myocytes
American Journal of Physiology-heart and Circulatory Physiology, 2008Co-Authors: Yejia Song, John C Shryock, Luiz BelardinelliAbstract:This study determined the role of a slowly inactivating component of sodium current (INa), late INa, to induce delayed Afterdepolarizations (DADs) and triggered activity. We hypothesized that an in...
-
ATP promotes development of Afterdepolarizations and triggered activity in cardiac myocytes.
American Journal of Physiology-Heart and Circulatory Physiology, 1994Co-Authors: Yejia Song, Luiz BelardinelliAbstract:The effect of extracellular ATP on transient inward current (Iti), delayed Afterdepolarization (DAD), early Afterdepolarization (EAD), and triggered activity were investigated in guinea pig isolated ventricular myocytes. ATP alone did not induce Afterdepolarizations nor did it significantly alter the resting membrane potentials and action potentials. However, when it was applied with drugs known to increase intracellular Ca2+, ATP facilitated the induction of Afterdepolarizations and triggered activity in approximately 60% of the cells. In the presence of isoproterenol, ATP increased the amplitude of Iti and DADs by 55 and 206%, respectively, and caused increases in the amplitude of L-type Ca2+ current (ICa) and EADs, which occasionally led to triggered activity. Similarly, addition of ATP increased the amplitude of Iti and DADs induced by elevated extracellular Ca2+ by 110 and 83%, respectively. Ryanodine inhibited the ATP-induced increase in Iti but not the increase in ICa. In the presence of BAY K 8644 or quinidine, ATP not only further prolonged the action potential durations by 18 +/- 4 and 17 +/- 4%, respectively, but also increased the amplitude of EADs. The present results show a novel arrhythmogenic effect of extracellular ATP, which facilitates the genesis of triggered arrhythmias when Ca2+ influx is increased, probably by further increasing Ca2+ influx from extracellular medium and Ca2+ release from intracellular stores.
-
Adenosine-sensitive Afterdepolarizations and triggered activity in guinea pig ventricular myocytes.
Circulation research, 1992Co-Authors: Yejia Song, S. Thedford, Bruce B. Lerman, Luiz BelardinelliAbstract:This study examines the cellular basis and specificity of the effects of adenosine on early Afterdepolarizations (EADs), delayed Afterdepolarizations (DADs), and triggered activity (TA) induced by various drugs with different mechanisms of action. Membrane potential and currents were measured in isolated guinea pig ventricular myocytes. Adenosine (10-100 microM) significantly (p less than 0.05) reduced the amplitude of DADs and suppressed TA induced by isoproterenol (10-50 nM) and forskolin (1 microM) but not those induced by dibutyryl cAMP (1 microM), ouabain (1-5 microM), and 7.2 mM [Ca2+]o. Adenosine also abolished EADs and TA induced by isoproterenol. In contrast, adenosine failed to abolish EADs and TA induced by quinidine (3 microM) or those that occurred spontaneously (i.e., in the absence of drugs). Transient inward current (ITi) was induced on repolarization after 2-second-long single depolarizing voltage steps or after 12-second-long trains of 300-msec depolarizing pulses. Concomitant with the attenuation of DADs, adenosine suppressed ITi caused by isoproterenol and forskolin but not those induced by ouabain, dibutyryl cAMP, and elevated [Ca2+]o. The amplitude of ITi was dependent on the magnitude of the activating voltage step, but the suppression of ITi by adenosine was not. The selective A1-adenosine receptor antagonist N-0861 (9-methyladenine derivative) antagonized the effects of adenosine on Afterdepolarizations, ITi, and TA. In myocytes from guinea pigs treated with pertussis toxin, adenosine failed to attenuate DADs and ITi or abolish TA induced by isoproterenol or forskolin. In parallel experiments, isoproterenol (10 nM) raised cellular cAMP from 5.7 +/- 0.2 to 8.1 +/- 0.1 pmol and the selective A1 receptor agonist cyclopentyladenosine (5 microM) reduced it to 6.5 +/- 0.2 pmol (p less than 0.05). Thus, adenosine specifically attenuates Afterdepolarizations and abolishes TA by suppressing ITiS that are associated with stimulation of adenylate cyclase via a pertussis toxin-sensitive A1 receptor-mediated action. In conclusion, the response of TA to adenosine may identify a mechanism of Afterdepolarization related to stimulation of adenylate cyclase.
James N Weiss - One of the best experts on this subject based on the ideXlab platform.
-
apamin sensitive calcium activated potassium currents in rabbit ventricles with chronic myocardial infarction
Journal of Cardiovascular Electrophysiology, 2013Co-Authors: Po-cheng Chang, Mitsunori Maruyama, Zhenhui Chen, Chiahsiang Hsueh, Hyung Wook Park, Kyoungsuk Rhee, Yucheng Hsieh, Changyu Shen, James N Weiss, Peng-sheng ChenAbstract:Small conductance calcium activated potassium (SK) currents are abundantly present in the neurons1, 2 and in atrial cardiomyocytes.3–6 However, little or no apamin-sensitive K currents are present in normal ventricles.3, 7, 8 These channels are activated by increases in intracellular Ca2+ (Cai) and are blocked by apamin.2 In the nervous system, activation of apamin-sensitive K+ current (IKAS) is responsible for slow afterhyperpolarizations, which help terminate neuronal action potential bursts.9 Similar to rapid neuronal discharges, ventricular fibrillation (VF) also causes Cai accumulation that may persist minutes after successful defibrillation.10 Cai accumulation and acute postshock action potential duration (APD) shortening facilitated the development of late phase 3 early Afterdepolarization (EAD)11 (also known as Cai transient triggered firing)12, 13 and electrical storm in that model. The acute postshock APD shortening in failing ventricles was shown to be due to IKAS activation.8 A more recent study by Chang et al14 showed that both the IKAS and the SK protein are increased in the native hearts of transplant recipients, and that apamin significantly prolongs the APD in failing human ventricular myocytes but not in normal control ventricular myocytes. These findings suggest that IKAS is important in ventricular repolarization and arrhythmogenesis in failing ventricles by shortening APD during Cai accumulation. However, the ability to accelerate the repolarization may also be antiarrhythmic. The redundancy in the complexities of myocardial repolarization (repolarization reserve)15 is important in maintaining normal and orderly ventricular repolarization, while reduced repolarization reserve underlies the mechanisms of Afterdepolarization and ventricular arrhythmias in congenital or acquired long-QT syndromes.16 Myocardial infarction (MI) is followed by significant arrhythmogenic ion-channel remodeling including downregulation of multiple K currents in the peri-infarct zone as well as in the subendocardial Purkinje fibers.17 These changes were thought to underlie the mechanisms of Afterdepolarizations and ventricular arrhythmias in MI ventricles. While K current remodeling after MI has been extensively studied, none of these studies included an evaluation of IKAS after MI. If there is an increased IKAS, it would counterbalance the downregulation of other K currents, hence maintaining repolarization reserve. Inhibition of IKAS by apamin would prolong the APD and reduce the repolarization reserve. The purpose of the present study was to perform optical mapping studies and patch clamp studies to test the hypothesis that IKAS is increased in rabbit ventricles with chronic MI and contributes significantly to ventricular repolarization in MI ventricles.
-
enhanced sensitivity of aged fibrotic hearts to angiotensin ii and hypokalemia induced early Afterdepolarization mediated ventricular arrhythmias
American Journal of Physiology-heart and Circulatory Physiology, 2012Co-Authors: Aneesh Bapat, James N Weiss, Thao P Nguyen, Jonghwan Lee, Ali A Sovari, Michael C Fishbein, Hrayr S KaragueuzianAbstract:Unlike young hearts, aged hearts are highly susceptible to early Afterdepolarization (EAD)-mediated ventricular fibrillation (VF). This differential may result from age-related structural remodelin...
-
Abstract 11220: Electrotonic Interactions Contribute to the Genesis of Phase-3 Early Afterdepolarizations and Triggered Activity in Acquired Long QT Syndrome
Circulation, 2010Co-Authors: Mitsunori Maruyama, Su-kiat Chua, Shien-fong Lin, Yuanfang Xie, Boyoung Joung, Seongwook Han, Tetsuji Shinohara, Mark J. Shen, James N WeissAbstract:Introduction: Both phase-2 and phase-3 early Afterdepolarizations (EADs) occur in long QT syndromes, with the latter proposed to be generated by spontaneous sarcoplasmic reticulum (SR) Ca release. ...
-
Tachycardia-induced early Afterdepolarizations: insights into potential ionic mechanisms from computer simulations.
Computers in biology and medicine, 2008Co-Authors: Ray B Huffaker, James N Weiss, Richard Samade, Boris KoganAbstract:Although early Afterdepolarizations (EADs) are classically thought to occur at slow heart rates, mounting evidence suggests that EADs may also occur at rapid heart rates produced by tachyarrhythmias, due to Ca overload of the sarcoplasmic reticulum (SR) leading to spontaneous SR Ca release. We hypothesized that the mechanism of tachycardia-induced EADs depends on the spatial and temporal morphology of spontaneous SR Ca release, and tested this hypothesis in computer simulations using a ventricular action potential mathematical model. Using two previously suggested spontaneous release morphologies, we found two distinct tachycardia-induced EAD mechanisms: one mechanistically similar to bradycardia-induced EADs, the other to delayed Afterdepolarizations (DADs).
-
Effects of early Afterdepolarizations on reentry in cardiac tissue: a simulation study
American journal of physiology. Heart and circulatory physiology, 2007Co-Authors: Ray B Huffaker, James N Weiss, Boris KoganAbstract:Early Afterdepolarizations (EADs) are classically generated at slow heart rates when repolarization reserve is reduced by genetic diseases or drugs. However, EADs may also occur at rapid heart rate...
Eric Schulze-bahr - One of the best experts on this subject based on the ideXlab platform.
-
Pauses after burst pacing provoke Afterdepolarizations and torsades de pointes in a patient with long QT syndrome.
Heart rhythm, 2004Co-Authors: Paulus Kirchhof, Stephan Zellerhoff, Gerold Mönnig, Eric Schulze-bahrAbstract:A patient with long QT syndrome and syncope underwent electrophysiological testing and recording of monophasic action potentials (MAP). Programmed ventricular stimulation using up to three premature stimuli did not provoke arrhythmias. Transient action potential prolongation and Afterdepolarizations were observed during pauses directly after high-rate fix frequent right ventricular burst pacing at 120–160 bpm. During the pause after burst pacing at 180 bpm, Afterdepolarizations at 16–19% amplitude of the MAP plateau persisted for several beats and preceded a short episode of torsades de pointes. High-rate burst pacing provoked Afterdepolarizations and triggered torsades de pointes in this patient with long QT syndrome.
Yue-hua Tan - One of the best experts on this subject based on the ideXlab platform.
-
Effects of berberine on delayed Afterdepolarizations in ventricular muscles in vitro and in vivo.
Journal of cardiovascular pharmacology, 1994Co-Authors: Yong-xiao Wang, Xiu Juan Yao, Yue-hua TanAbstract:The effects of berberine on delayed Afterdepolarizations in ventricular muscles in vitro and in vivo were investigated to help explain the mechanisms for its antiarrhythmic action. Berberine 3 mumol reduced the amplitude of delayed Afterdepolarizations induced by ouabain or posthypoxic reoxygenation and abolished subsequent triggered activity in isolated guinea pig right ventricular papillary muscles. At 30 mumol, it decreased the incidence of delayed Afterdepolarizations, associated with a further decrease in the amplitude of delayed Afterdepolarizations. In rabbit left ventricular (LV) muscles in vivo, berberine 1 mg/kg intravenously (i.v.) decreased the amplitude of delayed Afterdepolarizations evoked by ouabain and calcium gluconate from 9.6 +/- 1.9 to 6.8 +/- 0.8 mV and left stellate ganglion stimulation from 9.4 +/- 2.1 to 6.2 +/- 0.7 mV and blocked ventricular arrhythmias. After a 4-mg/kg i.v. bolus, the drug inhibited and even completely abolished development of delayed Afterdepolarizations, yet still reduced maximal velocity of depolarization in isolated and in vivo ventricular muscles. Therefore, one of the important mechanisms for antiarrhythmic action of berberine may be suppression of delayed Afterdepolarizations, which may be attributable in part to a decrease in Na+ influx.