ArticleBiophysical journal2012
In silico optimization of atrial fibrillation-selective sodium channel blocker pharmacodynamics.
Article in Biophysical journal, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed.
- Rational design, synthesis, and evaluation of novel polypharmacological compounds targeting NaThe Journal of biological chemistry · 2025Article
- Targeting the Substrate for Atrial Fibrillation: JACC Review Topic of the Week.Journal of the American College of Cardiology · 2024Review
- Why translation from basic discoveries to clinical applications is so difficult for atrial fibrillation and possible approaches to improving it.Cardiovascular research · 2021Review
- Rate-dependent effects of lidocaine on cardiac dynamics: Development and analysis of a low-dimensional drug-channel interaction model.PLoS computational biology · 2021Article
- Heart failure-induced atrial remodelling promotes electrical and conduction alternans.PLoS computational biology · 2020Article
- Understanding the Beat-to-Beat Variations of P-Waves Morphologies in AF Patients During Sinus Rhythm: A Scoping Review of the Atrial Simulation Studies.Frontiers in physiology · 2019Article
- Computational Modeling of Electrophysiology and Pharmacotherapy of Atrial Fibrillation: Recent Advances and Future Challenges.Frontiers in physiology · 2018Review
- Revealing kinetics and state-dependent binding properties of IChaos (Woodbury, N.Y.) · 2017Article
- Synergistic Anti-arrhythmic Effects in Human Atria with Combined Use of Sodium Blockers and Acacetin.Frontiers in physiology · 2017Article
- Anti-arrhythmic strategies for atrial fibrillation: The role of computational modeling in discovery, development, and optimization.Pharmacology & therapeutics · 2016Review
- Atrial-selective targeting of arrhythmogenic phase-3 early afterdepolarizations in human myocytes.Journal of molecular and cellular cardiology · 2016Article
- A Mathematical Model of Neonatal Rat Atrial Monolayers with Constitutively Active Acetylcholine-Mediated K+ Current.PLoS computational biology · 2016Article
- The value of basic research insights into atrial fibrillation mechanisms as a guide to therapeutic innovation: a critical analysis.Cardiovascular research · 2016Review
- The virtual heart as a platform for screening drug cardiotoxicity.British journal of pharmacology · 2015Review
- Comparison of Gating Properties and Use-Dependent Block of Nav1.5 and Nav1.7 Channels by Anti-Arrhythmics Mexiletine and Lidocaine.PloS one · 2015Article
- Pharmacology and Toxicology of Nav1.5-Class 1 anti-arrhythmic drugs.Cardiac electrophysiology clinics · 2014Article
- Mathematical approaches to understanding and imaging atrial fibrillation: significance for mechanisms and management.Circulation research · 2014Review
- Na(+) current expression in human atrial myofibroblasts: identity and functional roles.Frontiers in physiology · 2014Article
- Computational approaches to understand cardiac electrophysiology and arrhythmias.American journal of physiology. Heart and circulatory physiology · 2012Review
- Human atrial fibrillation: insights from computational electrophysiological models.Trends in cardiovascular medicine · 2011Review
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Atrial fibrillation (AF) is the most common type of clinical arrhythmia. Currently available anti-AF drugs are limited by only moderate efficacy and an unfavorable safety profile. Thus, there is a recognized need for improved antiarrhythmic agents with actions that are selective for the fibrillating atrium. State-dependent Na(+)-channel blockade potentially allows for the development of drugs with maximal actions on fibrillating atrial tissue and minimal actions on ventricular tissue at resting heart rates. In this study, we applied a mathematical model of state-dependent Na(+)-channel blocking (class I antiarrhythmic drug) action, along with mathematical models of canine atrial and ventricular cardiomyocyte action potentials, AF, and ventricular proarrhythmia, to determine the relationship between their pharmacodynamic properties and atrial-selectivity, AF-selectivity (atrial Na(+)-channel block at AF rates versus ventricular block at resting rates), AF-termination effectiveness, and ventricular proarrhythmic properties. We found that drugs that target inactivated channels are AF-selective, whereas drugs that target activated channels are not. The most AF-selective drugs were associated with minimal ventricular proarrhythmic potential and terminated AF in 33% of simulations; slightly fewer AF-selective agents achieved termination rates of 100% with low ventricular proarrhythmic potential. Our results define properties associated with AF-selective actions of class-I antiarrhythmic drugs and support the idea that it may be possible to develop class I antiarrhythmic agents with optimized pharmacodynamic properties for AF treatment.
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Registered trials
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