Calcium transient dynamics and the mechanisms of ventricular vulnerability to single premature electrical stimulation in Langendorff-perfused rabbit ventricles

Hayashi, Hideki; Kamanu, Santosh; Ono, Norihiko; Kawase, Ayaka; Chou, Chung Chuan; Weiss, James N.; Karagueuzian, Hrayr S.; Lin, Shien Fong; Chen, Peng Sheng

doi:10.1016/j.hrthm.2007.08.020

Cited by 10 publications

(7 citation statements)

References 15 publications

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“…Hearts were stimulated using a ramp pacing protocol [ 42 , 47 ] starting from the basic cycle length (CL) of 350 ms to shorter CL with 10-ms steps until either loss of 1:1 capture or VF induction. Ryanodine (2 μM) was perfused for 30 minutes, and the standard stimulation protocol was repeated.…”

Section: Methodsmentioning

confidence: 99%

Spatially Discordant Alternans and Arrhythmias in Tachypacing-Induced Cardiac Myopathy in Transgenic LQT1 Rabbits: The Importance of IKs and Ca2+ Cycling

et al. 2015

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BackgroundRemodeling of cardiac repolarizing currents, such as the downregulation of slowly activating K+ channels (IKs), could underlie ventricular fibrillation (VF) in heart failure (HF). We evaluated the role of I ks remodeling in VF susceptibility using a tachypacing HF model of transgenic rabbits with Long QT Type 1 (LQT1) syndrome.Methods and ResultsLQT1 and littermate control (LMC) rabbits underwent three weeks of tachypacing to induce cardiac myopathy (TICM). In vivo telemetry demonstrated steepening of the QT/RR slope in LQT1 with TICM (LQT1-TICM; pre: 0.26±0.04, post: 0.52±0.01, P<0.05). In vivo electrophysiology showed that LQT1-TICM had higher incidence of VF than LMC-TICM (6 of 11 vs. 3 of 11, respectively). Optical mapping revealed larger APD dispersion (16±4 vs. 38±6 ms, p<0.05) and steep APD restitution in LQT1-TICM compared to LQT1-sham (0.53±0.12 vs. 1.17±0.13, p<0.05). LQT1-TICM developed spatially discordant alternans (DA), which caused conduction block and higher-frequency VF (15±1 Hz in LQT1-TICM vs. 13±1 Hz in LMC-TICM, p<0.05). Ca2+ DA was highly dynamic and preceded voltage DA in LQT1-TICM. Ryanodine abolished DA in 5 out of 8 LQT1-TICM rabbits, demonstrating the importance of Ca2+ in complex DA formation. Computer simulations suggested that HF remodeling caused Ca2+-driven alternans, which was further potentiated in LQT1-TICM due to the lack of IKs.ConclusionsCompared with LMC-TICM, LQT1-TICM rabbits exhibit steepened APD restitution and complex DA modulated by Ca2+. Our results strongly support the contention that the downregulation of IKs in HF increases Ca2+ dependent alternans and thereby the risk of VF.

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Section: Methodsmentioning

confidence: 99%

Spatially Discordant Alternans and Arrhythmias in Tachypacing-Induced Cardiac Myopathy in Transgenic LQT1 Rabbits: The Importance of IKs and Ca2+ Cycling

et al. 2015

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“…The method has been used to track the sequences of electrical activation and force generation as well as cardiac repolarization and relaxation as a function of rate and sympathetic activity and during electrically induced ventricular fibrillation (VF) and defibrillation. Dual optical mapping has been playing an important role in elucidating arrhythmia mechanisms in models of heart failure (London et al, ), long QT syndrome (Choi et al, ), and ischemia/reperfusion (Choi and Salama, ; Lakireddy et al, ; Choi et al, ,b; Lakireddy et al, ), and in genetically altered animal models of human cardiac diseases (Katra et al, ; Katra and Laurita, ; Lan et al, ; London et al, ; Roell et al, ; Hayashi et al, ; Laurita and Rosenbaum, ; Saba et al, ).…”

Section: Introductionmentioning

confidence: 99%

Simultaneous Optical Mapping of Intracellular Free Calcium and Action Potentials from Langendorff Perfused Hearts

Salama

Hwang

2009

CP Cytometry

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The cardiac action potential (AP) controls the rise and fall of intracellular free Ca2+ (Cai), and thus the amplitude and kinetics of force generation. Besides excitation‐contraction coupling, the reverse process where Cai influences the AP through Cai‐dependent ionic currents has been implicated as the mechanism underlying QT alternans and cardiac arrhythmias in heart failure, ischemia/reperfusion, cardiac myopathy, myocardial infarction, congenital and drug‐induced long QT syndrome, and ventricular fibrillation. The development of dual optical mapping at high spatial and temporal resolution provides a powerful tool to investigate the role of Cai anomalies in eliciting cardiac arrhythmias. This unit describes experimental protocols to map APs and Cai transients from perfused hearts by labeling the heart with two fluorescent dyes, one to measure transmembrane potential (Vm), the other Cai transients. High spatial and temporal resolution is achieved by selecting Vm and Cai probes with the same excitation but different emission wavelengths, to avoid cross‐talk and mechanical components. Curr. Protoc. Cytom. 49:12.17.1‐12.17.32. © 2009 by John Wiley & Sons, Inc.

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“…Based on the results of the present study, it is reasonable to hypothesize that these postshock virtual electrodes can cause differential Ca i transients, with virtual anode sites generating larger Ca i transients than at the virtual cathode sites. 13, 27 Hwang et al 8 subsequently confirmed that there is postshock Ca i heterogeneity after near-threshold defibrillation shocks. The first beat of postshock activation always occurs from the Ca i sinkhole.…”

Section: Discussionmentioning

confidence: 94%

Intracellular Calcium and the Mechanism of Anodal Supernormal Excitability in Langendorff Perfused Rabbit Ventricles

Joung

Park

Maruyama

et al. 2011

Circ J

Self Cite

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Background Anodal stimulation hyperpolarizes cell membrane and increases intracellular Ca2+ (Cai) transient. This study tested the hypothesis that The maximum slope of Cai decline (–(dCai/dt)max) corresponds to the timing of anodal dip on the strength-interval curve and the initiation of repetitive responses and ventricular fibrillation (VF) after a premature stimulus (S2). Methods and Results We simultaneously mapped membrane potential (Vm) and Cai in 23 rabbit ventricles. A dip was observed on the anodal strength-interval curve. During the anodal dip, ventricles were captured by anodal break excitation directly under the S2 electrode. The Cai following anodal stimuli is larger than that following cathodal stimuli. The S1-S2 intervals of the anodal dip (203 ± 10 ms) coincided with the -(dCai/dt)max (199 ± 10 ms, p=NS). BAPTA-AM (n=3), INCX inhibition by low extracellular Na+ (n=3), and combined ryanodine and thapsigargin infusion (n=2) eliminated the anodal supernormality. Strong S2 during the relative refractory period (n=5) induced 29 repetitive responses and 10 VF episodes. The interval between S2 and the first non-driven beat was coincidental with the time of -(dCai/dt)max. Conclusions Larger Cai transient and INCX activation induced by anodal stimulation produces anodal supernormality. Time of maximum INCX activation is coincidental to the induction of non- driven beats from the Cai sinkhole after a strong premature stimulation.

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Calcium transient dynamics and the mechanisms of ventricular vulnerability to single premature electrical stimulation in Langendorff-perfused rabbit ventricles

Cited by 10 publications

References 15 publications

Spatially Discordant Alternans and Arrhythmias in Tachypacing-Induced Cardiac Myopathy in Transgenic LQT1 Rabbits: The Importance of IKs and Ca2+ Cycling

Spatially Discordant Alternans and Arrhythmias in Tachypacing-Induced Cardiac Myopathy in Transgenic LQT1 Rabbits: The Importance of IKs and Ca2+ Cycling

Simultaneous Optical Mapping of Intracellular Free Calcium and Action Potentials from Langendorff Perfused Hearts

Intracellular Calcium and the Mechanism of Anodal Supernormal Excitability in Langendorff Perfused Rabbit Ventricles

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