| Enhanced dispersion of repolarization and refractoriness in transgenic mouse hearts promotes reentrant ventricular tachycardia. | |
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MedLine Citation:
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PMID: 10700444 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The heterogeneous distribution of ion channels in ventricular muscle gives rise to spatial variations in action potential (AP) duration (APD) and contributes to the repolarization sequence in healthy hearts. It has been proposed that enhanced dispersion of repolarization may underlie arrhythmias in diseases with markedly different causes. We engineered dominant negative transgenic mice that have prolonged QT intervals and arrhythmias due to the loss of a slowly inactivating K(+) current. Optical techniques are now applied to map APs and investigate the mechanisms underlying these arrhythmias. Hearts from transgenic and control mice were isolated, perfused, stained with di-4-ANEPPS, and paced at multiple sites to optically map APs, activation, and repolarization sequences at baseline and during arrhythmias. Transgenic hearts exhibited a 2-fold prolongation of APD, less shortening (8% versus 40%) of APDs with decreasing cycle length, altered restitution kinetics, and greater gradients of refractoriness from apex to base compared with control hearts. A premature impulse applied at the apex of transgenic hearts produced sustained reentrant ventricular tachycardia (n=14 of 15 hearts) that did not occur with stimulation at the base (n=8) or at any location in control hearts (n=12). In transgenic hearts, premature impulses initiated reentry by encountering functional lines of conduction block caused by enhanced dispersion of refractoriness. Reentrant VT had stable (>30 minutes) alternating long/short APDs associated with long/short cycle lengths and T wave alternans. Thus, optical mapping of genetically engineered mice may help elucidate some electrophysiological mechanisms that underlie arrhythmias and sudden death in human cardiac disorders. |
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Authors:
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L C Baker; B London; B R Choi; G Koren; G Salama |
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Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Circulation research Volume: 86 ISSN: 1524-4571 ISO Abbreviation: Circ. Res. Publication Date: 2000 Mar |
Date Detail:
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Created Date: 2000-04-11 Completed Date: 2000-04-11 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0047103 Medline TA: Circ Res Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 396-407 Citation Subset: IM |
Affiliation:
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Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15261, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Action Potentials Animals Cardiac Pacing, Artificial / methods Electrophysiology Heart / physiopathology* Long QT Syndrome / genetics* Mice Mice, Transgenic / genetics* Neural Conduction Reaction Time Reference Values Refractory Period, Electrophysiological* Tachycardia, Ventricular / genetics*, physiopathology* |
| Grant Support | |
ID/Acronym/Agency:
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HL59614/HL/NHLBI NIH HHS; KO8-HL-02843/HL/NHLBI NIH HHS; R01-HL-57929/HL/NHLBI NIH HHS |
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