Document Detail


Nicorandil normalizes prolonged repolarisation in the first transgenic rabbit model with Long-QT syndrome 1 both in vitro and in vivo.
MedLine Citation:
PMID:  20959120     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Transgenic rabbits expressing loss-of-function pore mutants of the human gene KCNQ1 (K(v)LQT1-Y315S) have a Long QT-Syndrome 1 (LQT1) phenotype. We evaluated for the first time the effect of nicorandil, an opener of ATP-sensitive potassium channels, and of isoproterenol on cardiac action potential duration and heart rate dependent dispersion of repolarisation in transgenic LQT1 rabbits. In vivo LQT1 and littermate control were subjected to transvenous electrophysiological studies; in vitro monophasic action potentials were recorded from explanted Langendorff-perfused hearts. In vivo ventricular effective refractory periods (VERP) at the right ventricular base were significantly prolonged in LQT1 as compared to littermate control, resulting in a more pronounced VERP dispersion in LQT1. This difference in VERP dispersion between LQT1 and littermate control disappeared after infusion of nicorandil. In vitro, mean action potential durations (APD(75) and APD(90)) of LQT1 were significantly prolonged compared to littermate control at baseline. Nicorandil decreased APD(75) and APD(90) in LQT1 and littermate control at all stimulated heart rates. After adding nicorandil, the APD(90) at all hearts rates and the APD(75) at high heart rates were no longer different. Dispersion of repolarisation (∆APD(75) and ∆APD(90)) was heart rate dependently decreased after nicorandil at all tested stimulation cycle lengths only in LQT1. We demonstrated phenotypic differences of LQT1 and littermate control in vivo and in vitro. Nicorandil 20μmol/l improved repolarisation abnormalities and heterogeneities in transgenic LQT1 rabbits.
Authors:
Jürgen Biermann; Kezhong Wu; Katja E Odening; Stefan Asbach; Gideon Koren; Xuwen Peng; Manfred Zehender; Christoph Bode; Michael Brunner
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-10-17
Journal Detail:
Title:  European journal of pharmacology     Volume:  650     ISSN:  1879-0712     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2010-12-06     Completed Date:  2011-03-24     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  309-16     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier B.V. All rights reserved.
Affiliation:
Department of Cardiology and Angiology, University Hospital of Freiburg, Freiburg, Germany.
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MeSH Terms
Descriptor/Qualifier:
Action Potentials / drug effects*
Animals
Animals, Genetically Modified
Disease Models, Animal
Female
Heart / drug effects,  physiopathology
Humans
Male
Nicorandil / pharmacology*
Perfusion
Rabbits
Romano-Ward Syndrome / physiopathology*
Time Factors
Grant Support
ID/Acronym/Agency:
R01 HL046005/HL/NHLBI NIH HHS; R01 HL046005-18A1/HL/NHLBI NIH HHS; R01 HL046005-19/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
65141-46-0/Nicorandil
Comments/Corrections

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