ArticleCirculation. Arrhythmia and electrophysiology2012
Rate-dependent effects of vernakalant in the isolated non-remodeled canine left atria are primarily due to block of the sodium channel: comparison with ranolazine and dl-sotalol.
Article in Circulation. Arrhythmia and electrophysiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 47 citations in OpenAlex.
- Vernakalant is superior to ibutilide for achieving sinus rhythm in patients with recent-onset atrial fibrillation: a randomized controlled trial at the emergency department.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2017Trial
- Open channel block of Kv1.5 channels by HMQ1611.Frontiers in pharmacology · 2022Article
- Peptide Inhibitors of Kv1.5: An Option for the Treatment of Atrial Fibrillation.Pharmaceuticals (Basel, Switzerland) · 2021Review
- New Strategies for the Treatment of Atrial Fibrillation.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Effects of Ranolazine and its Combination with Amiodarone on Rapid Pacing-induced Reentrant Atrial Tachycardia in Rabbits.The Journal of innovations in cardiac rhythm management · 2021Article
- Investigational Anti-Atrial Fibrillation Pharmacology and Mechanisms by Which Antiarrhythmics Terminate the Arrhythmia: Where Are We in 2020?Journal of cardiovascular pharmacology · 2020Review
- The Small Conductance Calcium-Activated Potassium Channel Inhibitors NS8593 and UCL1684 Prevent the Development of Atrial Fibrillation Through Atrial-Selective Inhibition of Sodium Channel Activity.Journal of cardiovascular pharmacology · 2020Article
- Atrial Heterogeneity Generates Re-entrant Substrate during Atrial Fibrillation and Anti-arrhythmic Drug Action: Mechanistic Insights from Canine Atrial Models.PLoS computational biology · 2016Article
- Mechanisms underlying atrial-selective block of sodium channels by Wenxin Keli: Experimental and theoretical analysis.International journal of cardiology · 2016Article
- Role of Calcium-activated Potassium Channels in Atrial Fibrillation Pathophysiology and Therapy.Journal of cardiovascular pharmacology · 2015Review
- The vernakalant story: how did it come to approval in Europe and what is the delay in the U.S.A?Current cardiology reviews · 2014Review
- Vernakalant for the conversion of atrial fibrillation: the new kid on the block?Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc · 2014Review
- Antiarrhythmic drugs 2013: state of the art.Current cardiology reports · 2013Review
- Atrial selectivity of antiarrhythmic drugs.The Journal of physiology · 2013Review
- Role of late sodium channel current block in the management of atrial fibrillation.Cardiovascular drugs and therapy · 2013Review
- Safety and efficacy of vernakalant for acute cardioversion of atrial fibrillation: an update.Vascular health and risk management · 2013Review
- Atrial-selective prolongation of refractory period with AVE0118 is due principally to inhibition of sodium channel activity.Journal of cardiovascular pharmacology · 2012Article
- Vernakalant versus ibutilide for immediate conversion of recent-onset atrial fibrillation.HippokratiaArticle
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundSeveral clinical trials have shown that vernakalant is effective in terminating recent onset atrial fibrillation (AF). The electrophysiological actions of vernakalant are not fully understood. METHODS AND
resultsHere we report the results of a blinded study comparing the in vitro canine atrial electrophysiological effects of vernakalant, ranolazine, and dl-sotalol. Action potential durations (APD(50,75,90)), effective refractory period (ERP), post repolarization refractoriness (PRR), maximum rate of rise of the action potential (AP) upstroke (V(max)), diastolic threshold of excitation (DTE), conduction time (CT), and the shortest S(1)-S(1) permitting 1:1 activation (S(1)-S(1)) were measured using standard stimulation and microelectrode recording techniques in isolated normal, non-remodeled canine arterially perfused left atrial preparations. Vernakalant caused variable but slight prolongation of APD(90) (P=not significant), but significant prolongation of APD(50) at 30 μmol/L and rapid rates. In contrast, ranolazine and dl-sotalol produced consistent concentration- and reverse rate-dependent prolongation of APD(90). Vernakalant and ranolazine caused rate-dependent, whereas dl-sotalol caused reverse rate-dependent, prolongation of ERP. Significant rate-dependent PRR developed with vernakalant and ranolazine, but not with dl-sotalol. Other sodium channel-mediated parameters (ie, V(max), CT, DTE, and S(1)-S(1)) also were depressed significantly by vernakalant and ranolazine, but not by dl-sotalol. Only vernakalant elevated AP plateau voltage, consistent with blockade of ultrarapid delayed rectified potassium current and transient outward potassium current.
conclusionsIn isolated canine left atria, the effects of vernakalant and ranolazine were characterized by use-dependent inhibition of sodium channel-mediated parameters, and those of dl-sotalol by reverse rate-dependent prolongation of APD(90) and ERP. This suggests that during the rapid activation rates of AF, the I(Na) blocking action of the mixed ion channel blocker vernakalant takes prominence. This mechanism may explain vernakalant's anti-AF efficacy.
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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.