Linked Life Data

10517739

Source:http://linkedlifedata.com/resource/pubmed/id/10517739

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
1999-11-4
pubmed:abstractText
BACKGROUND: The Brugada syndrome is characterized by marked ST-segment elevation in the right precordial ECG leads and is associated with a high incidence of sudden and unexpected arrhythmic death. Our study examines the cellular basis for this syndrome. METHODS AND RESULTS: Using arterially perfused wedges of canine right ventricle (RV), we simultaneously recorded transmembrane action potentials from 2 epicardial and 1 endocardial sites, together with unipolar electrograms and a transmural ECG. Loss of the action potential dome in epicardium but not endocardium after exposure to pinacidil (2 to 5 micromol/L), a K(+) channel opener, or the combination of a Na(+) channel blocker (flecainide, 7 micromol/L) and acetylcholine (ACh, 2 to 3 micromol/L) resulted in an abbreviation of epicardial response and a transmural dispersion of repolarization, which caused an ST-segment elevation in the ECG. ACh facilitated loss of the action potential dome, whereas isoproterenol (0.1 to 1 micromol/L) restored the epicardial dome, thus reducing or eliminating the ST-segment elevation. Heterogeneous loss of the dome caused a marked dispersion of repolarization within the epicardium and transmurally, thus giving rise to phase 2 reentrant extrasystole, which precipitated ventricular tachycardia (VT) and ventricular fibrillation (VF). Transient outward current (I(to)) block with 4-aminopyridine (1 to 2 mmol/L) or quinidine (5 micromol/L) restored the dome, normalized the ST segment, and prevented VT/VF. Conclusions-Depression or loss of the action potential dome in RV epicardium creates a transmural voltage gradient that may be responsible for the ST-segment elevation observed in the Brugada syndrome and other syndromes exhibiting similar ECG manifestations. Our results also demonstrate that extrasystolic activity due to phase 2 reentry can arise in the intact wall of the canine RV and serve as the trigger for VT/VF. Our data point to I(to) block (4-aminopyridine, quinidine) as an effective pharmacological treatment.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1524-4539
pubmed:author
pubmed:issnType
Electronic
pubmed:day
12
pubmed:volume
100
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1660-6
pubmed:dateRevised
2011-7-22
pubmed:meshHeading
pubmed-meshheading:10517739-Acetylcholine, pubmed-meshheading:10517739-Action Potentials, pubmed-meshheading:10517739-Adrenergic alpha-Agonists, pubmed-meshheading:10517739-Adrenergic beta-Agonists, pubmed-meshheading:10517739-Animals, pubmed-meshheading:10517739-Cardiac Complexes, Premature, pubmed-meshheading:10517739-Death, Sudden, Cardiac, pubmed-meshheading:10517739-Dogs, pubmed-meshheading:10517739-Electrocardiography, pubmed-meshheading:10517739-Genetic Heterogeneity, pubmed-meshheading:10517739-Heart Conduction System, pubmed-meshheading:10517739-Heart Ventricles, pubmed-meshheading:10517739-Humans, pubmed-meshheading:10517739-Isoproterenol, pubmed-meshheading:10517739-Quinidine, pubmed-meshheading:10517739-Sodium Channels, pubmed-meshheading:10517739-Syndrome, pubmed-meshheading:10517739-Ventricular Fibrillation
pubmed:year
1999
pubmed:articleTitle
Cellular basis for the Brugada syndrome and other mechanisms of arrhythmogenesis associated with ST-segment elevation.
pubmed:affiliation
Masonic Medical Research Laboratory, Utica, NY, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't