Document Detail


ST segment elevation by current-to-load mismatch: an experimental and computational study.
MedLine Citation:
PMID:  20870038     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
BACKGROUND: Recently, we demonstrated that ajmaline caused ST segment elevation in the heart of an SCN5A mutation carrier by excitation failure in structurally discontinuous myocardium. In patients with Brugada syndrome, ST segment elevation is modulated by cardiac sodium (I(Na)), transient outward (I(to)), and L-type calcium currents (I(CaL)).
OBJECTIVE: To establish experimentally whether excitation failure by current-to-load mismatch causes ST segment elevation and is modulated by I(to) and I(CaL).
METHODS: In porcine epicardial shavings, isthmuses of 0.9, 1.1, or 1.3 mm in width were created parallel to the fiber orientation. Local activation was recorded electrically or optically (di-4-ANEPPS) simultaneously with a pseudo-electrocardiogram (ECG) before and after ajmaline application. Intra- and extracellular potentials and ECGs were simulated in a computer model of the heart and thorax before and after introduction of right ventricular structural discontinuities and during varying levels of I(Na), I(to), and I(CaL).
RESULTS: In epicardial shavings, conduction blocked after ajmaline in a frequency-dependent manner in all preparations with isthmuses ≤ 1.1 mm width. Total conduction block occurred in three of four preparations with isthmuses of 0.9 mm versus one of seven with isthmuses ≥ 1.1 mm (P<.05). Excitation failure resulted in ST segment elevation on the pseudo-ECG. In computer simulations, subepicardial structural discontinuities caused local activation delay and made the success of conduction sensitive to I(Na), I(to), and I(CaL). Reduction of I(to) and increase of I(CaL) resulted in a higher excitatory current, overcame subepicardial excitation failure, and reduced the ST segment elevation.
CONCLUSIONS: Excitation failure by current-to-load mismatch causes ST segment elevation and, like ST segment elevation in Brugada patients, is modulated by I(to) and I(CaL).
Authors:
Mark G Hoogendijk; Mark Potse; Alain Vinet; Jacques M T de Bakker; Ruben Coronel
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-10-30
Journal Detail:
Title:  Heart rhythm : the official journal of the Heart Rhythm Society     Volume:  8     ISSN:  1556-3871     ISO Abbreviation:  Heart Rhythm     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2010-12-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101200317     Medline TA:  Heart Rhythm     Country:  United States    
Other Details:
Languages:  eng     Pagination:  111-8     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Heart Rhythm Society. All rights reserved.
Affiliation:
Department of Experimental Cardiology, Heart Failure Research Center, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. m.g.hoogendijk@amc.uva.nl
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Comment In:
Heart Rhythm. 2011 Jan;8(1):119-20   [PMID:  20920601 ]

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