ArticleBritish journal of pharmacology2010
Robust anti-arrhythmic efficacy of verapamil and flunarizine against dofetilide-induced TdP arrhythmias is based upon a shared and a different mode of action.
Article in British journal of pharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 38 citations in OpenAlex.
- Arrhythmia Inducibility in the CAVB Dog Model, A Critical Analysis on Underlying Factors.Cardiovascular toxicology · 2025Article
- The canine chronic atrioventricular block model in cardiovascular preclinical drug research.British journal of pharmacology · 2022Review
- The Increment of Short-term Variability of Repolarisation Determines the Severity of the Imminent Arrhythmic Outcome.Arrhythmia & electrophysiology review · 2019Review
- Selective late sodium current inhibitor GS-458967 suppresses Torsades de Pointes by mostly affecting perpetuation but not initiation of the arrhythmia.British journal of pharmacology · 2018Article
- Risk of QT prolongation and torsade de pointes associated with exposure to hydroxyzine: re-evaluation of an established drug.Pharmacology research & perspectives · 2017Article
- Short-term Variability of Repolarization Is Superior to Other Repolarization Parameters in the Evaluation of Diverse Antiarrhythmic Interventions in the Chronic Atrioventricular Block Dog.Journal of cardiovascular pharmacology · 2017Review
- The high frequency relationship: implications for torsadogenic hERG blockers.British journal of pharmacology · 2016Article
- Short-term variability in QT interval and ventricular arrhythmias induced by dofetilide are dependent on high-frequency autonomic oscillations.British journal of pharmacology · 2015Article
- Verapamil increases the bactericidal activity of bedaquiline against Mycobacterium tuberculosis in a mouse model.Antimicrobial agents and chemotherapy · 2015Article
- The electromechanical window is no better than QT prolongation to assess risk of Torsade de Pointes in the complete atrioventricular block model in dogs.British journal of pharmacology · 2014Article
- Ions, equations and electrons: the evolving role of computer simulations in cardiac electrophysiology safety evaluations.British journal of pharmacology · 2012Article
- Verapamil as an antiarrhythmic agent in congestive heart failure: hopping from rabbit to human?British journal of pharmacology · 2012Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeThe high predisposition to Torsade de Pointes (TdP) in dogs with chronic AV-block (CAVB) is well documented. The anti-arrhythmic efficacy and mode of action of Ca(2+) channel antagonists, flunarizine and verapamil against TdP were investigated. EXPERIMENTAL APPROACH: Mongrel dogs with CAVB were selected based on the inducibility of TdP with dofetilide. The effects of flunarizine and verapamil were assessed after TdP and in different experiments to prevent dofetilide-induced TdP. Electrocardiogram and ventricular monophasic action potentials were recorded. Electrophysiological parameters and short-term variability of repolarization (STV) were determined. In vitro, flunarizine and verapamil were added to determine their effect on (i) dofetilide-induced early after depolarizations (EADs) in canine ventricular myocytes (VM); (ii) diastolic Ca(2+) sparks in RyR2(R4496+/+) mouse myocytes; and (iii) peak and late I(Na) in SCN5A-HEK 293 cells. KEY
resultsDofetilide increased STV prior to TdP and in VM prior to EADs. Both flunarizine and verapamil completely suppressed TdP and reversed STV to baseline values. Complete prevention of TdP was achieved with both drugs, accompanied by the prevention of an increase in STV. Suppression of EADs was confirmed after flunarizine. Only flunarizine blocked late I(Na). Ca(2+) sparks were reduced with verapamil. CONCLUSIONS AND IMPLICATIONS: Robust anti-arrhythmic efficacy was seen with both Ca(2+) channel antagonists. Their divergent electrophysiological actions may be related to different additional effects of the two drugs.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.