ArticleJCI insight2020
Altered calcium handling produces reentry-promoting action potential alternans in atrial fibrillation-remodeled hearts.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 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
30 citing papers in PubMed, 63 citations in OpenAlex.
- Trial
- Colchicine initiated before radiofrequency-induced injury attenuates left atrial inflammation, fibrosis, and susceptibility to atrial fibrillation.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
- The clinical pathophysiology of atrial fibrillation: outstanding questions from bedside to bench and back.Physiological reviews · 2026Review
- Versatile hiPSC Models and Bioengineering Platforms for Investigation of Atrial Fibrosis and Fibrillation.Cells · 2026Review
- Calcium Homeostatic Feedback Control Predicts Atrial Fibrillation Initiation, Remodeling, and Progression.JACC. Clinical electrophysiology · 2025Article
- Electrophysiological Mechanisms and Therapeutic Potential of Calcium Channels in Atrial Fibrillation.Reviews in cardiovascular medicine · 2025Review
- Remodeling of the cardiac striatin interactome and its dynamics in the diabetic heart.Scientific reports · 2025Article
- Enhanced prevention on postoperative atrial fibrillation by using anti-inflammatory biodegradable drug patch.Regenerative biomaterials · 2025Article
- "Pharmacological" analysis of atrial fibrillation maintenance mechanism: reentry, wavelets, or focal?Frontiers in cardiovascular medicine · 2025Review
- Assaying sarcoplasmic reticulum CaBiophysics reports · 2024Article
- Atrial Fibrillation and Underlying Structural and Electrophysiological Heterogeneity.International journal of molecular sciences · 2024Review
- Article
- Brain-to-heart cholinergic synapse-calcium signaling mediates ischemic stroke-induced atrial fibrillation.Theranostics · 2024Article
- RyR2 inhibition with dantrolene is antiarrhythmic, prevents further pathological remodeling, and improves cardiac function in chronic ischemic heart disease.Journal of molecular and cellular cardiology · 2023Article
- Advances in basic and translational research in atrial fibrillation.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- IncreasedInternational journal of cardiology. Heart & vasculature · 2023Article
- Increased β1-adrenergic receptor antibody confers a vulnerable substrate for atrial fibrillation via mediating Ca2+ mishandling and atrial fibrosis in active immunization rabbit models.Clinical science (London, England : 1979) · 2023Article
- Targeted Atrial Fibrillation Therapy and Risk Stratification Using Atrial Alternans.Journal of cardiovascular development and disease · 2023Review
- Cardiac Alternans: From Bedside to Bench and Back.Circulation research · 2023Review
- Predictive value of TRPV2 expression from peripheral blood mononuclear cells on the early recurrence of atrial fibrillation after radiofrequency catheter ablation.BMC cardiovascular disorders · 2022Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 4 countries.
Funding
Abstract
Atrial fibrillation (AF) alters atrial cardiomyocyte (ACM) Ca2+ handling, promoting ectopic beat formation. We examined the effects of AF-associated remodeling on Ca2+-related action potential dynamics and consequences for AF susceptibility. AF was maintained electrically in dogs by right atrial (RA) tachypacing. ACMs isolated from AF dogs showed increased Ca2+ release refractoriness, spontaneous Ca2+ spark frequency, and cycle length (CL) threshold for Ca2+ and action potential duration (APD) alternans versus controls. AF increased the in situ CL threshold for Ca2+/APD alternans and spatial dispersion in Ca2+ release recovery kinetics, leading to spatially discordant alternans associated with reentrant rotor formation and susceptibility to AF induction/maintenance. The clinically available agent dantrolene reduced Ca2+ leak and CL threshold for Ca2+/APD alternans in ACMs and AF dog right atrium, while suppressing AF susceptibility; caffeine increased Ca2+ leak and CL threshold for Ca2+/APD alternans in control dog ACMs and RA tissues. In vivo, the atrial repolarization alternans CL threshold was increased in AF versus control, as was AF vulnerability. Intravenous dantrolene restored repolarization alternans threshold and reduced AF vulnerability. Immunoblots showed reduced expression of total and phosphorylated ryanodine receptors and calsequestrin in AF and unchanged phospholamban/SERCA expression. Thus, along with promoting spontaneous ectopy, AF-induced Ca2+ handling abnormalities favor AF by enhancing vulnerability to repolarization alternans, promoting initiation and maintenance of reentrant activity; dantrolene provides a lead molecule to target this mechanism.
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Registered trials
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.