| Carvedilol Analogue Inhibits Triggered Activities Evoked by Both Early and Delayed Afterdepolarizations. | |
| | |
MedLine Citation:
|
PMID: 22982970 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
BACKGROUND: Carvedilol and its analogues suppress delayed afterdepolarizations (DADs) and catecholaminergic polymorphic ventricular tachycardias by direct action on the cardiac ryanodine receptor (RyR2). OBJECTIVE: We tested a hypothesis that carvedilol analogue may also prevent triggered activities (TAs) through the suppression of early afterdepolarizations (EADs). METHODS: Intracellular Ca(2+) and membrane voltage were simultaneously recorded using optical mapping technique in Langendorff-perfused mouse and rabbit hearts to study the effect of carvedilol analogue, VK-II-36 that does not have significant beta-blocking effects. RESULTS: Spontaneous intracellular Ca(2+) elevations (SCaEs) during diastole was induced by rapid ventricular pacing and isoproterenol infusion in intact rabbit ventricles. Systolic and diastolic SCaEs were simultaneously noted in Langendorff-perfused RyR2 R4496(+/-) mouse hearts after creating atrioventricular block. VK-II-36 effectively suppressed SCaEs and eliminated TAs observed in both mouse and rabbit ventricles. We tested the effect of VK-II-36 on EADs using a rabbit model of acquired long QT syndrome in which phase-2 and phase-3 EADs were observed in association with systolic SCaEs. VK-II-36 abolished the systolic SCaEs and phase-2 EADs, and greatly decreased the dispersion of repolarization and the amplitude of phase-3 EADs. VK-II-36 completely prevented EAD-mediated TAs in all ventricles studied. CONCLUSION: A carvedilol analogue, VK-II-36 inhibits ventricular tachyarrhythmias in intact mouse and rabbit ventricles by suppression of SCaEs, independent of beta-blocking activity. The RyR2 may be a potential target for treating focal ventricular arrhythmias triggered by either EADs or DADs. |
| | |
Authors:
|
Mitsunori Maruyama; Jianmin Xiao; Qiang Zhou; Kannan Vembaiyan; Su-Kiat Chua; Michael Rubart-von der Lohe; Shien-Fong Lin; Thomas G Back; Sr Wayne Chen; Peng-Sheng Chen |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2012-9-13 |
Journal Detail:
|
Title: Heart rhythm : the official journal of the Heart Rhythm Society Volume: - ISSN: 1556-3871 ISO Abbreviation: Heart Rhythm Publication Date: 2012 Sep |
Date Detail:
|
Created Date: 2012-9-17 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 101200317 Medline TA: Heart Rhythm Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
|
Copyright © 2012. Published by Elsevier Inc. |
Affiliation:
|
Krannert Institute of Cardiology and the Division of Cardiology, Department of Medicine,Indiana University School of Medicine, Indianapolis, Indiana, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Transforming Growth Factor ß1 Level and Outcome after Catheter Ablation for Non-paroxysmal Atrial F...
Next Document: Progressive and accelerated disability onset by race/ethnicity and education among late midlife and ...