Document Detail


Effects of bepridil versus E-4031 on transmural ventricular repolarization and inducibility of ventricular tachyarrhythmias in the dog.
MedLine Citation:
PMID:  20487341     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Bepridil (a multiple channel blocker) may markedly prolong the QT interval and induce polymorphic ventricular tachyarrhythmias (VTA). We compared the transmural ventricular repolarization characteristics and inducibility of polymorphic VTA after administration of bepridil versus the pure I(Kr) blocker, E-4031, each administered to five open-chest dogs.
METHODS: We used plunge needle electrode to record transmural left ventricular (LV) repolarization and activation-recovery interval (ARI) to estimate local repolarization. The correlation between paced cycle length and ARI was separately examined in the LV endocardium, mid-myocardium (Mid), and epicardium. Attempts to induce VTA were made during bradycardia and sympathetic stimulation.
RESULTS: Bepridil and E-4031 prolonged QT interval and ARI in all LV layers, though the magnitude of prolongation was greatest in Mid, increasing the transmural ARI dispersion, particularly during bradycardia. Compared with E-4031, bepridil caused mild, reverse use-dependent changes in ventricular repolarization, and less ARI dispersion than E-4031 during slow ventricular pacing. Both drugs increased ARI(max) and cycle length at 50% of ARI(max), though the changes were smaller after bepridil than after E-4031 administration. Bradycardia after the administration of each drug induced no VTA; however, sympathetic stimulation induced sustained polymorphic VTA in two of five dogs treated with E-4031 versus no dog treated with bepridil.
CONCLUSIONS: Unlike the pure I(kr) blocker, E-4031, bepridil exhibited weak properties of reverse use-dependency and protected against sympathetic stimulation-induced VTA. It may be an effective supplemental treatment for recipients of implantable cardioverter defibrillator.
Authors:
Daisuke Izumi; Masaomi Chinushi; Kenichi Iijima; Shizue Ahara; Satoru Komura; Hiroshi Furushima; Yukio Hosaka; Akiko Sanada; Nobue Yagihara; Yoshifusa Aizawa
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-05-04
Journal Detail:
Title:  Pacing and clinical electrophysiology : PACE     Volume:  33     ISSN:  1540-8159     ISO Abbreviation:  Pacing Clin Electrophysiol     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-08-13     Completed Date:  2010-12-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7803944     Medline TA:  Pacing Clin Electrophysiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  950-9     Citation Subset:  IM    
Affiliation:
First Department of Internal Medicine, Niigata University School of Medicine, Niigata, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anti-Arrhythmia Agents / pharmacology*
Bepridil / pharmacology*
Blood Pressure
Calcium Channel Blockers / pharmacology*
Cerebral Revascularization
Dogs
Electrophysiologic Techniques, Cardiac
Heart Rate / drug effects
Piperidines / pharmacology*
Pyridines / pharmacology*
Tachycardia, Ventricular / physiopathology*
Ventricular Function, Left / drug effects*
Chemical
Reg. No./Substance:
0/Anti-Arrhythmia Agents; 0/Calcium Channel Blockers; 0/Piperidines; 0/Pyridines; 113558-89-7/E 4031; 64706-54-3/Bepridil

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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