ArticleBritish journal of pharmacology2012
Blockade of I(Ca) suppresses early afterdepolarizations and reduces transmural dispersion of repolarization in a whole heart model of chronic heart failure.
Article in British journal of pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 31 citations in OpenAlex.
- Bifurcations and Proarrhythmic Behaviors in Cardiac Electrical Excitations.Biomolecules · 2022Review
- Safe electrophysiologic profile of dexmedetomidine in different experimental arrhythmia models.Scientific reports · 2021Article
- PDE5 Inhibition Suppresses Ventricular Arrhythmias by Reducing SR CaCirculation research · 2021Article
- Integrative and theoretical research on the architecture of a biological system and its disorder.The journal of physiological sciences : JPS · 2019Review
- BlindedFrontiers in pharmacology · 2019Article
- Multiple Dynamical Mechanisms of Phase-2 Early Afterdepolarizations in a Human Ventricular Myocyte Model:Frontiers in physiology · 2019Article
- Barbaloin inhibits ventricular arrhythmias in rabbits by modulating voltage-gated ion channels.Acta pharmacologica Sinica · 2018Article
- Early afterdepolarisation tendency as a simulated pro-arrhythmic risk indicator.Toxicology research · 2017Article
- Drug-Induced QT/QTc Interval Shortening: Lessons from Drug-Induced QT/QTc Prolongation.Drug safety · 2016Review
- Drug-induced proarrhythmia: risk factors and electrophysiological mechanisms.Nature reviews. Cardiology · 2016Review
- Article
- Effects of wenxin keli on the action potential and L-type calcium current in rats with transverse aortic constriction-induced heart failure.Evidence-based complementary and alternative medicine : eCAM · 2013Article
- Molecular basis of cardioprotective effect of antioxidant vitamins in myocardial infarction.BioMed research international · 2013Review
- The physiology of cardiac calcium handling.Wiener medizinische Wochenschrift (1946) · 2012Review
- Calcium handling and ventricular tachyarrhythmias.Wiener medizinische Wochenschrift (1946) · 2012Review
- Verapamil as an antiarrhythmic agent in congestive heart failure: hopping from rabbit to human?British journal of pharmacology · 2012Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND PURPOSE Chronic heart failure (CHF) is associated with action potential prolongation and Ca(2+) overload, increasing risk of ventricular tachyarrhythmias (VT). We therefore investigated whether I(Ca) blockade was anti-arrhythmic in an intact perfused heart model of CHF. EXPERIMENTAL APPROACH CHF was induced in rabbits after 4 weeks of rapid ventricular pacing. Hearts from CHF and sham-operated rabbits were isolated and perfused (Langendorff preparation), with ablation of the AV node. VT was induced by erythromycin and low [K(+) ] (1.5mM). Electrophysiology of cardiac myocytes, with block of cation currents, was simulated by a mathematical model. KEY RESULTS Repolarization was prolonged in CHF hearts compared with sham-operated hearts. Action potential duration (APD) and overall dispersion of repolarization were further increased by erythromycin (300 µM) to block I(Kr) in CHF hearts. After lowering [K(+) ] to 1.5mM, CHF and sham hearts showed spontaneous episodes of polymorphic non-sustained VT. Additional infusion of verapamil (0.75 µM) suppressed early afterdepolarizations (EAD) and VT in 75% of sham and CHF hearts. Verapamil shortened APD and dispersion of repolarization, mainly by reducing transmural dispersion of repolarization via shortening of endocardial action potentials. Mathematical simulations showed that EADs were more effectively reduced by verapamil assuming a state-dependent block than a simple block of I(Ca) . CONCLUSIONS AND IMPLICATIONS Blockade of I(Ca) was highly effective in suppressing VT via reduction of transmural dispersion of repolarization and suppression of EAD. Such blockade might represent a novel therapeutic option to reduce risk of VT in structurally normal hearts and also in heart failure. LINKED ARTICLE This article is commented on by Stams et al., pp. 554-556 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476-5381.2011.01818.x.
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