ArticleHeart rhythm2015
Delayed afterdepolarizations generate both triggers and a vulnerable substrate promoting reentry in cardiac tissue.
Article in Heart rhythm, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed.
- Associations between specific non-sustained ventricular tachycardia characteristics and sudden cardiac death in hypertrophic cardiomyopathy.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 · 2026Article
- T-World Virtual Human Cardiomyocyte. I. Development, Validation, and Cell Arrhythmogenesis.Circulation research · 2026Article
- Ephaptic coupling and the source-sink effect of cardiac conduction.The Journal of physiology · 2026Article
- Occupational stress, cardiovascular vulnerability and sudden cardiac death in police officers: mechanisms and the protective role of structured exercise.Frontiers in public health · 2026Review
- Abnormal calcium release and delayed afterdepolarizations: A comparison of two mathematical models for human ventricular myocytes.PloS one · 2026Article
- Methadone Blockade of Inward Rectifier Potassium Current Promotes Both Early and Delayed Repolarization Arrhythmias: Mechanistic Insights From Computational Modeling.Journal of the American Heart Association · 2025Article
- Disruption of ventricular activation by subthreshold delayed afterdepolarizations in RyR2-R420Q catecholaminergic polymorphic ventricular tachycardia.Journal of molecular and cellular cardiology plus · 2025Article
- Finding the right balance of RyR2 phosphorylation for arrhythmia prevention.Nature cardiovascular research · 2025Article
- COMPUTATIONAL ANALYSIS OF THE NOVEL LQT3 MUTATIONS G1481V AND Q1491H IN MYOCARDIAL AND PURKINJE CELLS.Annual Modeling and Simulation Conference (ANNSIM). Annual Modeling and Simulation Conference (Online) · 2025Article
- T-World: A highly general computational model of a human ventricular myocyte.bioRxiv : the preprint server for biology · 2025Article
- An hiPSC-CM approach for electrophysiological phenotyping of a patient-specific case of short-coupled TdP.Stem cell research & therapy · 2024Article
- Mechanistic Relevance of Ventricular Arrhythmias in Heart Failure with Preserved Ejection Fraction.International journal of molecular sciences · 2024Review
- RyR cooperativity and mobile buffers: functional clues to the resolution of the cardiac calcium wave problem?The Journal of physiology · 2024Article
- Cell-to-cell heterogeneity in ion channel conductance impacts substrate vulnerability to arrhythmia.American journal of physiology. Heart and circulatory physiology · 2024Article
- Curvature-mediated source and sink effects on the genesis of premature ventricular complexes in long QT syndrome.American journal of physiology. Heart and circulatory physiology · 2024Article
- Isolated Cardiac Ryanodine Receptor Function Varies Between Mammals.The Journal of membrane biology · 2024Article
- Genetic and Molecular Underpinnings of Atrial Fibrillation.NPJ cardiovascular health · 2024Article
- Identification and characterization of two novel KCNH2 mutations contributing to long QT syndrome.PloS one · 2024Article
- Mechanisms of pulmonary arterial hypertension-induced atrial fibrillation: insights from multi-scale models of the human atria.Interface focus · 2023Article
- Patchy fibrosis promotes trigger-substrate interactions that both generate and maintain atrial fibrillation.Interface focus · 2023Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
backgroundDelayed afterdepolarizations (DADs) have been well characterized as arrhythmia triggers, but their role in generating a tissue substrate vulnerable to reentry is not well understood.
objectiveThe purpose of this study was to test the hypothesis that random DADs can self-organize to generate both an arrhythmia trigger and a vulnerable substrate simultaneously in cardiac tissue as a result of gap junction coupling.
methodsComputer simulations in 1-dimensional cable and 2-dimensional tissue models were performed. The cellular DAD amplitude was varied by changing the strength of sarcoplasmic reticulum calcium release. Random DAD latency and amplitude in different cells were simulated using gaussian distributions.
resultsDepending on the strength of spontaneous sarcoplasmic reticulum calcium release and other conditions, random DADs in cardiac tissue resulted in the following behaviors: (1) triggered activity (TA); (2) a vulnerable tissue substrate causing unidirectional conduction block and reentry by inactivating sodium channels; (3) both triggers and a vulnerable substrate simultaneously by generating TA in regions next to regions with subthreshold DADs susceptible to unidirectional conduction block and reentry. The probability of the latter 2 behaviors was enhanced by reduced sodium channel availability, reduced gap junction coupling, increased tissue heterogeneity, and less synchronous DAD latency.
conclusionDADs can self-organize in tissue to generate arrhythmia triggers, a vulnerable tissue substrate, and both simultaneously. Reduced sodium channel availability and gap junction coupling potentiate this mechanism of arrhythmias, which are relevant to a variety of heart disease conditions.
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