ArticleHeart rhythm2013
Carvedilol analogue inhibits triggered activities evoked by both early and delayed afterdepolarizations.
Article in Heart rhythm, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 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
10 citing papers in PubMed, 22 citations in OpenAlex.
- Optical mapping: pioneering the frontier of preclinical antiarrhythmic drug evaluation.iScience · 2026Review
- Comparing the Efficacy of Carvedilol and Flecainide on the Treatment of Idiopathic Premature Ventricular Complexes from Ventricular Outflow Tract: A Multicenter, Randomized, Open-Label Pilot Study.Journal of clinical medicine · 2023Article
- Impact of R-Carvedilol on β2-Adrenergic Receptor-Mediated Spontaneous Calcium Release in Human Atrial Myocytes.Biomedicines · 2022Article
- Emerging Antiarrhythmic Drugs for Atrial Fibrillation.International journal of molecular sciences · 2022Review
- Ventricular Arrhythmias in Ischemic Cardiomyopathy-New Avenues for Mechanism-Guided Treatment.Cells · 2021Review
- Simultaneous recordings of action potentials and calcium transients from human induced pluripotent stem cell derived cardiomyocytes.Biology open · 2018Article
- Modulation of the QT interval duration in hypertension with antihypertensive treatment.Hypertension research : official journal of the Japanese Society of Hypertension · 2015Review
- The importance of Ca(2+)-dependent mechanisms for the initiation of the heartbeat.Frontiers in physiology · 2015Review
- Carvedilol analog modulates both basal and stimulated sinoatrial node automaticity.Heart and vessels · 2014Article
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10 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundCarvedilol and its analogues suppress delayed afterdepolarizations (DADs) and catecholaminergic polymorphic ventricular tachycardias by direct action on the cardiac ryanodine receptor type 2 (RyR2).
objectiveTo test a hypothesis that carvedilol analogue may also prevent triggered activities (TAs) through the suppression of early afterdepolarizations (EADs).
methodsIntracellular Ca(2+) and membrane voltage were simultaneously recorded by using optical mapping technique in Langendorff-perfused mouse and rabbit hearts to study the effect of carvedilol analogue VK-II-36, which does not have significant beta-blocking effects.
resultsSpontaneous intracellular Ca(2+) elevations (SCaEs) during diastole were induced by rapid ventricular pacing and isoproterenol infusion in intact rabbit ventricles. Systolic and diastolic SCaEs were simultaneously noted in Langendorff-perfused RyR2 R4496(+/-) mouse hearts after creating atrioventricular block. VK-II-36 effectively suppressed SCaEs and eliminated TAs observed in both mouse and rabbit ventricles. We tested the effect of VK-II-36 on EADs by using a rabbit model of acquired long QT syndrome, in which phase 2 and phase 3 EADs were observed in association with systolic SCaEs. VK-II-36 abolished the systolic SCaEs and phase 2 EADs, and greatly decreased the dispersion of repolarization and the amplitude of phase 3 EADs. VK-II-36 completely prevented EAD-mediated TAs in all ventricles studied.
conclusionsA carvedilol analogue, VK-II-36, inhibits ventricular tachyarrhythmias in intact mouse and rabbit ventricles by the suppression of SCaEs, independent of beta-blocking activity. The RyR2 may be a potential target for treating focal ventricular arrhythmias triggered by either EADs or DADs.
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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.