| Cytosolic calcium accumulation and delayed repolarization associated with ventricular arrhythmias in a guinea pig model of Andersen-Tawil syndrome. | |
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MedLine Citation:
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PMID: 20380896 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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BACKGROUND: Andersen-Tawil syndrome (ATS1)-associated ventricular arrhythmias are initiated by frequent, hypokalemia-exacerbated, triggered activity. Previous ex vivo studies in drug-induced Andersen-Tawil syndrome (DI-ATS1) models have proposed that arrhythmia propensity in DI-ATS1 derives from cytosolic Ca(2+) ([Ca(2+)](i)) accumulation leading to increased triggered activity. OBJECTIVE: The purpose of this study was to test the hypothesis that elevated [Ca(2+)](i) with concomitant APD prolongation, rather than APD dispersion, underlies arrhythmia propensity during DI-ATS1. METHODS: DI-ATS1 was induced in isolated guinea pig ventricles by perfusion of 2 mM KCl Tyrode solution containing 10 μM BaCl(2). APD and [Ca(2+)](i) from the anterior epicardium were quantified by ratiometric optical voltage (di-4-ANEPPS) or Ca(2+) (Indo-1) mapping during right ventricular pacing with or without the ATP-sensitive potassium channel opener pinacidil (15 μM). RESULTS: APD gradients under all conditions were insufficient for arrhythmia induction by programmed stimulation. However, 38% of DI-ATS1 preparations experienced ventricular tachycardias (VTs), and all preparations experienced a high incidence of premature ventricular complexes (PVCs). Pinacidil decreased APD and APD dispersion and reduced VTs (to 6%), and PVC frequency (by 79.5%). However, PVC frequency remained significantly greater relative to control (0.5% ± 0.3% of DI-ATS1). Importantly, increased arrhythmia propensity during DI-ATS1 was associated with diastolic [Ca(2+)](i) accumulation and increased [Ca(2+)](i) transient amplitudes. Pinacidil partially attenuated the former but did not alter the latter. CONCLUSION: The study data suggest that arrhythmias during DI-ATS1 may be a result of triggered activity secondary to prolonged APD and altered [Ca(2+)](i) cycling and less likely dependent on large epicardial APD gradients forming the substrate for reentry. Therefore, therapies aimed at reducing [Ca(2+)](i) rather than APD gradients may prove effective in treatment of ATS1. |
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Authors:
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Przemysław B Radwański; Rengasayee Veeraraghavan; Steven Poelzing |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-04-07 |
Journal Detail:
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Title: Heart rhythm : the official journal of the Heart Rhythm Society Volume: 7 ISSN: 1556-3871 ISO Abbreviation: Heart Rhythm Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-09-27 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101200317 Medline TA: Heart Rhythm Country: United States |
Other Details:
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Languages: eng Pagination: 1428-1435.e1 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved. |
Affiliation:
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Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, Utah 84112-5000, USA. |
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Descriptor/Qualifier:
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| Grant Support | |
ID/Acronym/Agency:
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R21 HL094828-01A1/HL/NHLBI NIH HHS |
| Comments/Corrections | |
Comment In:
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Heart Rhythm. 2010 Oct;7(10):1436-7
[PMID:
20430114
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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