ArticleCardiovascular research2009
Re-evaluating the efficacy of beta-adrenergic agonists and antagonists in long QT-3 syndrome through computational modelling.
Article in Cardiovascular research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 27 citations in OpenAlex.
- Computational modeling of cardiac electrophysiology and arrhythmogenesis: toward clinical translation.Physiological reviews · 2024Review
- Exploring mutation specific beta blocker pharmacology of the pathogenic late sodium channel current from patient-specific pluripotent stem cell myocytes derived from long QT syndrome mutation carriers.Channels (Austin, Tex.) · 2022Article
- The Efficacy of Beta-Blockers in Patients With Long QT Syndrome 1-3 According to Individuals' Gender, Age, and QTc Intervals: A Network Meta-analysis.Frontiers in pharmacology · 2020Review
- R-From-T as a Common Mechanism of Arrhythmia Initiation in Long QT Syndromes.Circulation. Arrhythmia and electrophysiology · 2019Article
- Computational models in cardiology.Nature reviews. Cardiology · 2019Review
- A Heart for Diversity: Simulating Variability in Cardiac Arrhythmia Research.Frontiers in physiology · 2018Review
- Revealing the Concealed Nature of Long-QT Type 3 Syndrome.Circulation. Arrhythmia and electrophysiology · 2017Article
- Molecular Pathophysiology of Congenital Long QT Syndrome.Physiological reviews · 2017Review
- The Beta Adrenergic Receptor Blocker Propranolol Counteracts Retinal Dysfunction in a Mouse Model of Oxygen Induced Retinopathy: Restoring the Balance between Apoptosis and Autophagy.Frontiers in cellular neuroscience · 2017Article
- The virtual heart as a platform for screening drug cardiotoxicity.British journal of pharmacology · 2015Review
- Deranged sodium to sudden death.The Journal of physiology · 2015Review
- Computational Models for Predictive Cardiac Ion Channel Pharmacology.Drug discovery today. Disease models · 2014Article
- Interpreting genetic effects through models of cardiac electromechanics.American journal of physiology. Heart and circulatory physiology · 2012Review
- Computational approaches to understand cardiac electrophysiology and arrhythmias.American journal of physiology. Heart and circulatory physiology · 2012Review
- Cardiac myocytes and local signaling in nano-domains.Progress in biophysics and molecular biology · 2011Review
- Integrative systems models of cardiac excitation-contraction coupling.Circulation research · 2011Review
- Cardiac models in drug discovery and development: a review.Critical reviews in biomedical engineering · 2011Review
- Propranolol blocks cardiac and neuronal voltage-gated sodium channels.Frontiers in pharmacology · 2010Article
- Molecular determinants of local anesthetic action of beta-blocking drugs: Implications for therapeutic management of long QT syndrome variant 3.Journal of molecular and cellular cardiology · 2010Article
- Using computational modeling to predict arrhythmogenesis and antiarrhythmic therapy.Drug discovery today. Disease models · 2009Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
aimsLong QT syndrome (LQTS) is a heterogeneous collection of inherited cardiac ion channelopathies characterized by a prolonged electrocardiogram QT interval and increased risk of sudden cardiac death. Beta-adrenergic blockers are the mainstay of treatment for LQTS. While their efficacy has been demonstrated in LQTS patients harbouring potassium channel mutations, studies of beta-blockers in subtype 3 (LQT3), which is caused by sodium channel mutations, have produced ambiguous results. In this modelling study, we explore the effects of beta-adrenergic drugs on the LQT3 phenotype. METHODS AND
resultsIn order to investigate the effects of beta-adrenergic activity and to identify sources of ambiguity in earlier studies, we developed a computational model incorporating the effects of beta-agonists and beta-blockers into an LQT3 mutant guinea pig ventricular myocyte model. Beta-activation suppressed two arrhythmogenic phenomena, transmural dispersion of repolarization and early after depolarizations, in a dose-dependent manner. However, the ability of beta-activation to prevent cardiac conduction block was pacing-rate-dependent. Low-dose beta-blockade by propranolol reversed the beneficial effects of beta-activation, while high dose (which has off-target sodium channel effects) decreased arrhythmia susceptibility.
conclusionThese results demonstrate that beta-activation may be protective in LQT3 and help to reconcile seemingly conflicting results from different experimental models. They also highlight the need for well-controlled clinical investigations re-evaluating the use of beta-blockers in LQT3 patients.
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Registered trials
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