ArticleCardiovascular research2018
Normal interventricular differences in tissue architecture underlie right ventricular susceptibility to conduction abnormalities in a mouse model of Brugada syndrome.
Article in Cardiovascular research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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.
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Who cites it
24 citing papers in PubMed, 38 citations in OpenAlex.
- Consequences of Right Heart Disease for Cardiac Electrophysiology and Arrhythmias: Cellular and Structural Mechanisms.CJC open · 2025Review
- NMDA-Type Glutamate Receptor Activation Promotes Ischemic Arrhythmias by Targeting the AKT1-TBX3-Nav1.5 Axis.Acta physiologica (Oxford, England) · 2025Article
- Genetic background determines the severity of age-dependent cardiac structural abnormalities and arrhythmia susceptibility in Scn5a-1798insD mice.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 · 2024Article
- A comprehensive protocol combining in vivo and ex vivo electrophysiological experiments in an arrhythmogenic animal model.American journal of physiology. Heart and circulatory physiology · 2024Article
- Patient-specific iPSC-derived cardiomyocytes reveal aberrant activation of Wnt/β-catenin signaling in SCN5A-related Brugada syndrome.Stem cell research & therapy · 2023Article
- Brugada Syndrome: More than a Monogenic Channelopathy.Biomedicines · 2023Review
- Electrical and Structural Insights into Right Ventricular Outflow Tract Arrhythmogenesis.International journal of molecular sciences · 2023Review
- Transcription factor Meis1 act as a new regulator of ischemic arrhythmias in mice.Journal of advanced research · 2022Article
- Electrophysiology and Arrhythmogenesis in the Human Right Ventricular Outflow Tract.Circulation. Arrhythmia and electrophysiology · 2022Article
- Review
- ESC working group on cardiac cellular electrophysiology position paper: relevance, opportunities, and limitations of experimental models for cardiac electrophysiology research.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 · 2021Review
- Fibroblast Growth Factor 21 Ameliorates NaFrontiers in pharmacology · 2021Article
- Novel Optics-Based Approaches for Cardiac Electrophysiology: A Review.Frontiers in physiology · 2021Review
- Anisotropic Cardiac Conduction.Arrhythmia & electrophysiology review · 2020Review
- Incorporating Latent Variables Using Nonnegative Matrix Factorization Improves Risk Stratification in Brugada Syndrome.Journal of the American Heart Association · 2020Article
- An Appreciation of Anatomy in the Molecular World.Journal of cardiovascular development and disease · 2020Review
- Mechanisms of Arrhythmias in the Brugada Syndrome.International journal of molecular sciences · 2020Review
- Multiphoton intravital microscopy in small animals: motion artefact challenges and technical solutions.Journal of microscopy · 2020Review
- "Heart Oddity": Intrinsically Reduced Excitability in the Right Ventricle Requires Compensation by Regionally Specific Stress Kinase Function.Frontiers in physiology · 2020Review
- Experimental Models of Brugada syndrome.International journal of molecular sciences · 2019Review
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
Aims: Loss-of-function of the cardiac sodium channel NaV1.5 is a common feature of Brugada syndrome. Arrhythmias arise preferentially from the right ventricle (RV) despite equivalent NaV1.5 downregulation in the left ventricle (LV). The reasons for increased RV sensitivity to NaV1.5 loss-of-function mutations remain unclear. Because ventricular electrical activation occurs predominantly in the transmural axis, we compare RV and LV transmural electrophysiology to determine the underlying cause of the asymmetrical conduction abnormalities in Scn5a haploinsufficient mice (Scn5a+/-). Methods and results: Optical mapping and two-photon microscopy in isolated-perfused mouse hearts demonstrated equivalent depression of transmural conduction velocity (CV) in the LV and RV of Scn5a+/- vs. wild-type littermates. Only RV transmural conduction was further impaired when challenged with increased pacing frequencies. Epicardial dispersion of activation and beat-to-beat variation in activation time were increased only in the RV of Scn5a+/- hearts. Analysis of confocal and histological images revealed larger intramural clefts between cardiomyocyte layers in the RV vs. LV, independent of genotype. Acute sodium current inhibition in wild type hearts using tetrodotoxin reproduced beat-to-beat activation variability and frequency-dependent CV slowing in the RV only, with the LV unaffected. The influence of clefts on conduction was examined using a two-dimensional monodomain computational model. When peak sodium channel conductance was reduced to 50% of normal the presence of clefts between cardiomyocyte layers reproduced the activation variability and conduction phenotype observed experimentally. Conclusions: Normal structural heterogeneities present in the RV are responsible for increased vulnerability to conduction slowing in the presence of reduced sodium channel function. Heterogeneous conduction slowing seen in the RV will predispose to functional block and the initiation of re-entrant ventricular arrhythmias.
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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.