ArticlePloS one2015
Spatially Discordant Alternans and Arrhythmias in Tachypacing-Induced Cardiac Myopathy in Transgenic LQT1 Rabbits: The Importance of IKs and Ca2+ Cycling.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 26 citations in OpenAlex.
- Spontaneous Repolarization Alternans Causes VT/VF Rearrest That Is Suppressed by Preserving Gap Junctions.JACC. Clinical electrophysiology · 2024Article
- Mechanistic insights into spontaneous transition from cellular alternans to ventricular fibrillation.Physiological reports · 2023Article
- Cardiac Alternans: From Bedside to Bench and Back.Circulation research · 2023Review
- Synchronization of spatially discordant voltage and calcium alternans in cardiac tissue.Physical review. E · 2022Article
- Mitochondrial depolarization promotes calcium alternans: Mechanistic insights from a ventricular myocyte model.PLoS computational biology · 2021Article
- Stability of spatially discordant repolarization alternans in cardiac tissue.Chaos (Woodbury, N.Y.) · 2020Article
- Delayed global feedback in the genesis and stability of spatiotemporal excitation patterns in paced biological excitable media.PLoS computational biology · 2020Article
- Spatially Discordant Repolarization Alternans in the Absence of Conduction Velocity Restitution.Biophysical journal · 2020Article
- Transgenic Rabbit Models in Proarrhythmia Research.Frontiers in pharmacology · 2020Review
- Cilantro leaf harbors a potent potassium channel-activating anticonvulsant.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Mechanisms linking T-wave alternans to spontaneous initiation of ventricular arrhythmias in rabbit models of long QT syndrome.The Journal of physiology · 2018Article
- SK channel enhancers attenuate Ca2+-dependent arrhythmia in hypertrophic hearts by regulating mito-ROS-dependent oxidation and activity of RyR.Cardiovascular research · 2017Article
- Alternans in atria: Mechanisms and clinical relevance.Medicina (Kaunas, Lithuania) · 2017Review
- Cardiac dynamics: Alternans and arrhythmogenesis.Journal of arrhythmia · 2016Review
- Article
Corrections and comments
- Erratum issuedCorrection: Spatially Discordant Alternans and Arrhythmias in Tachypacing-Induced Cardiac Myopathy in Transgenic LQT1 Rabbits: The Importance of IKs and Ca2+ Cycling.2015 · Zhen, Song [corrected to Song, Zhen]
Authors and funding
15 authors at 4 institutions in 1 country.
Funding
Abstract
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 Iks 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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