ArticlePflugers Archiv : European journal of physiology2011
Refractory dispersion promotes conduction disturbance and arrhythmias in a Scn5a (+/-) mouse model.
Article in Pflugers Archiv : European journal of physiology, 2011. 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, 25 citations in OpenAlex.
- Cardiac arrhythmogenesis: roles of ion channels and their functional modification.Frontiers in physiology · 2024Review
- Prognostic value of right ventricular refractory period heterogeneity in Brugada syndrome. Independent predictor or part of something more complex? Author's reply.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 · 2023Article
- Prognostic value of right ventricular refractory period heterogeneity in Type-1 Brugada electrocardiographic pattern.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 · 2023Article
- Brugada Syndrome: Different Experimental Models and the Role of Human Cardiomyocytes From Induced Pluripotent Stem Cells.Journal of the American Heart Association · 2022Review
- Reduced cardiomyocyte NaJournal of cellular physiology · 2019Article
- Ventricular pro-arrhythmic phenotype, arrhythmic substrate, ageing and mitochondrial dysfunction in peroxisome proliferator activated receptor-γ coactivator-1β deficient (Pgc-1βMechanisms of ageing and development · 2018Article
- Multiple targets for flecainide action: implications for cardiac arrhythmogenesis.British journal of pharmacology · 2018Review
- Epac-induced ryanodine receptor type 2 activation inhibits sodium currents in atrial and ventricular murine cardiomyocytes.Clinical and experimental pharmacology & physiology · 2018Article
- Cardiomyocyte ionic currents in intact young and aged murine Pgc-1βMechanisms of ageing and development · 2018Article
- Determination of action potential wavelength restitution inJournal of geriatric cardiology : JGC · 2017Article
- An infrared optical pacing system for screening cardiac electrophysiology in human cardiomyocytes.PloS one · 2017Article
- Murine Electrophysiological Models of Cardiac Arrhythmogenesis.Physiological reviews · 2017Review
- Variability in local action potential durations, dispersion of repolarization and wavelength restitution in aged wild-type and Scn5aJournal of geriatric cardiology : JGC · 2016Article
- The RyR2-P2328S mutation downregulates Nav1.5 producing arrhythmic substrate in murine ventricles.Pflugers Archiv : European journal of physiology · 2016Article
- Electrophysiological Mechanisms of Brugada Syndrome: Insights from Pre-clinical and Clinical Studies.Frontiers in physiology · 2016Review
- Optogenetic determination of the myocardial requirements for extrasystoles by cell type-specific targeting of ChannelRhodopsin-2.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Flecainide exerts paradoxical effects on sodium currents and atrial arrhythmia in murine RyR2-P2328S hearts.Acta physiologica (Oxford, England) · 2015Article
- Mouse Models of SCN5A-Related Cardiac Arrhythmias.Frontiers in physiology · 2012Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Accentuated right ventricular (RV) gradients in action potential duration (APD) have been implicated in the arrhythmogenicity observed in Brugada syndrome in studies assuming that ventricular effective refractory periods (VERPs) vary in concert with APDs. The present experiments use a genetically modified mouse model to explore spatial heterogeneities in VERP that in turn might affect conduction velocity, thereby causing arrhythmias. Activation latencies, APDs and VERPs recorded during programmed S1S2 protocols were compared in RV and left ventricular (LV) epicardia and endocardia of Langendorff-perfused wild-type (WT) and Scn5a (+/-) hearts. Scn5a (+/-) and WT hearts showed similar patterns of shorter VERPs in RV than LV epicardia, and in epicardia than endocardia. However, Scn5a (+/-) hearts showed longer VERPs, despite shorter APD(90)s, than WT in all regions examined. The pro- and anti-arrhythmic agents flecainide and quinidine increased regional VERPs despite respectively decreasing and increasing the corresponding APD(90)s particularly in Scn5a (+/-) RV epicardia. In contrast, Scn5a (+/-) hearts showed greater VERP gradients between neighbouring regions, particularly RV transmural gradients, than WT (9.1 ± 1.1 vs. 5.7 ± 0.5 ms, p < 0.05, n = 12). Flecainide increased (to 21 ± 0.9 ms, p < 0.05, n = 6) but quinidine decreased (to 4.5 ± 0.5 ms, p < 0.05, n = 6) these gradients, particularly across the Scn5a (+/-) RV. Finally, Scn5a (+/-) hearts showed greater conduction slowing than WT following S2 stimuli, particularly with flecainide administration. Rather than arrhythmogenesis resulting from increased transmural repolarization gradients in an early, phase 2, reentrant excitation mechanism, the present findings implicate RV VERP gradients in potential reentrant mechanisms involving impulse conduction slowed by partial refractoriness.
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