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Paradoxical effects of KB-R7943 on arrhythmogenicity in a chronic myocardial infarction rabbit model.
MedLine Citation:
PMID:  25241015     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND: Na(+)/Ca(2+) exchanger blockade has been reported to be anti-arrhythmic in different models. The effects of KB-R7943, a Na(+)/Ca(2+) exchanger blocker, on arrhythmogenesis in hearts with chronic myocardial infarction (MI) remain unclear.
METHODS: Dual voltage and intracellular Ca(2+) (Cai) optical mapping was performed in nine rabbit hearts with chronic MI and four control hearts. Electrophysiology studies including inducibility of ventricular tachyarrhythmias, ventricular fibrillation dominant frequency, action potential, Cai alternans, Cai decay, and conduction velocity were performed. The same protocol was repeated in the presence of KB-R7943 (0.5, 1, and 5μM) after the baseline studies.
RESULTS: KB-R7943 was effective in suppressing afterdepolarizations and spontaneous ventricular tachyarrhythmias in hearts with chronic MI. Surprisingly, KB-R7943 increased the inducibility of ventricular tachyarrhythmias in a dose-dependent manner (11%, 11%, 22%, and 56% at baseline and with 0.5, 1, and 5μM KB-R7943, respectively, p=0.02). Optical mapping analysis revealed that the underlying mechanisms of the induced ventricular tachyarrhythmias were probably spatially discordant alternans with wave breaks and rotors. Further analysis showed that KB-R7943 significantly enhanced both action potential (p=0.033) and Cai (p=0.001) alternans, prolonged Cai decay (tau value) in a dose-dependent manner (p=0.004), and caused heterogeneous conduction delay especially at peri-infarct zones during rapid burst pacing. In contrast, KB-R7943 had insignificant effects in control hearts.
CONCLUSIONS: In this chronic MI rabbit model, KB-R7943 has contrasting effects on arrhythmogenesis, suppressing afterdepolarizations and spontaneous ventricular tachyarrhythmias, but enhancing the inducibility of tachyarrhythmias. The mechanism is probably the enhanced spatially discordant alternans because of prolonged Cai decay and heterogeneous conduction delay.
Authors:
Po-Cheng Chang; Hung-Ta Wo; Hui-Ling Lee; Ming-Shien Wen; Chung-Chuan Chou
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-9-15
Journal Detail:
Title:  Journal of cardiology     Volume:  -     ISSN:  1876-4738     ISO Abbreviation:  J Cardiol     Publication Date:  2014 Sep 
Date Detail:
Created Date:  2014-9-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8804703     Medline TA:  J Cardiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014. Published by Elsevier Ltd.
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