ArticleCirculation. Arrhythmia and electrophysiology2015
Synchronous systolic subcellular Ca2+-elevations underlie ventricular arrhythmia in drug-induced long QT type 2.
Article in Circulation. Arrhythmia and electrophysiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 21 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
21 citing papers in PubMed, 35 citations in OpenAlex.
- 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
- Advancements in understanding cardiotoxicity of EGFR- TKIs in non-small cell lung cancer treatment and beyond.Frontiers in pharmacology · 2024Review
- Initiation of ventricular arrhythmia in the acquired long QT syndrome.Cardiovascular research · 2023Article
- Activation of small conductance CaThe Journal of physiology · 2023Article
- Directed graph mapping shows rotors maintain non-terminating and focal sources maintain self-terminating Torsade de Pointes in canine model.Frontiers in physiology · 2023Article
- R-on-T and the initiation of reentry revisited: Integrating old and new concepts.Heart rhythm · 2022Article
- PDE5 Inhibition Suppresses Ventricular Arrhythmias by Reducing SR CaCirculation research · 2021Article
- Canard analysis reveals why a large Ca2+ window current promotes early afterdepolarizations in cardiac myocytes.PLoS computational biology · 2020Article
- Balance Between Rapid Delayed Rectifier KCirculation. Arrhythmia and electrophysiology · 2020Article
- In silico investigation of the mechanisms underlying atrial fibrillation due to impaired Pitx2.PLoS computational biology · 2020Article
- R-From-T as a Common Mechanism of Arrhythmia Initiation in Long QT Syndromes.Circulation. Arrhythmia and electrophysiology · 2019Article
- Multiple Dynamical Mechanisms of Phase-2 Early Afterdepolarizations in a Human Ventricular Myocyte Model:Frontiers in physiology · 2019Article
- Autonomic conflict exacerbates long QT associated ventricular arrhythmias.Journal of molecular and cellular cardiology · 2018Article
- Genomic upregulation of cardiac Cav1.2α and NCX1 by estrogen in women.Biology of sex differences · 2017Article
- Global Optimization of Ventricular Myocyte Model to Multi-Variable Objective Improves Predictions of Drug-Induced Torsades de Pointes.Frontiers in physiology · 2017Article
- Spontaneous initiation of premature ventricular complexes and arrhythmias in type 2 long QT syndrome.American journal of physiology. Heart and circulatory physiology · 2016Article
- Improved Prediction of Drug-Induced Torsades de Pointes Through Simulations of Dynamics and Machine Learning Algorithms.Clinical pharmacology and therapeutics · 2016Article
- The link between abnormal calcium handling and electrical instability in acquired long QT syndrome--Does calcium precipitate arrhythmic storms?Progress in biophysics and molecular biology · 2016Review
- QT Adaptation and Intrinsic QT Variability in Congenital Long QT Syndrome.Journal of the American Heart Association · 2015Article
- Dual Vm/Ca imaging of premature ventricular contractions: bridging the gap of anatomical scales.Circulation. Arrhythmia and electrophysiology · 2015Article
Corrections and comments
- Commented on by
- Erratum issuedCorrection.2015
Authors and funding
4 authors at 1 institution in 2 countries.
Funding
Abstract
backgroundRepolarization delay is a common clinical problem, which can promote ventricular arrhythmias. In myocytes, abnormal sarcoplasmic reticulum Ca(2+)-release is proposed as the mechanism that causes early afterdepolarizations, the cellular equivalent of ectopic-activity in drug-induced long-QT syndrome. A crucial missing link is how such a stochastic process can overcome the source-sink mismatch to depolarize sufficient ventricular tissue to initiate arrhythmias. METHODS AND
resultsOptical maps of action potentials and Ca(2+)-transients from Langendorff rabbit hearts were measured at low (150×150 μm(2)/pixel) and high (1.5×1.5 μm(2)/pixel) resolution before and during arrhythmias. Drug-induced long QT type 2, elicited with dofetilide inhibition of IKr (the rapid component of rectifying K+ current), produced spontaneous Ca(2+)-elevations during diastole and systole, before the onset of arrhythmias. Diastolic Ca(2+-)waves appeared randomly, propagated within individual myocytes, were out-of-phase with adjacent myocytes, and often died-out. Systolic secondary Ca(2+-)elevations were synchronous within individual myocytes, appeared 188±30 ms after the action potential-upstroke, occurred during high cytosolic Ca(2+) (40%-60% of peak-Ca(2+)-transients), appeared first in small islands (0.5×0.5 mm(2)) that enlarged and spread throughout the epicardium. Synchronous systolic Ca(2+-)elevations preceded voltage-depolarizations (9.2±5 ms; n=5) and produced pronounced Spatial Heterogeneities of Ca(2+)-transient-durations and action potential-durations. Early afterdepolarizations originating from sites with the steepest gradients of membrane-potential propagated and initiated arrhythmias. Interestingly, more complex subcellular Ca(2+)-dynamics (multiple chaotic Ca(2+)-waves) occurred during arrhythmias. K201, a ryanodine receptor stabilizer, eliminated Ca(2+)-elevations and arrhythmias.
conclusionsThe results indicate that systolic and diastolic Ca(2+)-elevations emanate from sarcoplasmic reticulum Ca(2+)-release and systolic Ca(2+)-elevations are synchronous because of high cytosolic and luminal-sarcoplasmic reticulum Ca(2+), which overcomes source-sink mismatch to trigger arrhythmias in intact hearts.
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