ArticleBritish journal of pharmacology2007
Potentiation of E-4031-induced torsade de pointes by HMR1556 or ATX-II is not predicted by action potential short-term variability or triangulation.
Article in British journal of pharmacology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 33 citations in OpenAlex.
- Human perinatal stem cell derived extracellular matrix enables rapid maturation of hiPSC-CM structural and functional phenotypes.Scientific reports · 2020Article
- Contribution of ion currents to beat-to-beat variability of action potential duration in canine ventricular myocytes.Pflugers Archiv : European journal of physiology · 2015Article
- Clarithromycin, QTc interval prolongation and torsades de pointes: the need to study case reports.Therapeutic advances in infectious disease · 2013Article
- Investigation of mechanism of drug-induced cardiac injury and torsades de pointes in cynomolgus monkeys.British journal of pharmacology · 2012Article
- Biomarkers and endogenous determinants of dofetilide-induced torsades de pointes in α(1) -adrenoceptor-stimulated, anaesthetized rabbits.British journal of pharmacology · 2010Article
- Minimizing repolarization-related proarrhythmic risk in drug development and clinical practice.Drugs · 2010Review
- Dog left ventricular midmyocardial myocytes for assessment of drug-induced delayed repolarization: short-term variability and proarrhythmic potential.British journal of pharmacology · 2010Article
- The role of the Na+/Ca2+ exchanger, I(Na) and I(CaL) in the genesis of dofetilide-induced torsades de pointes in isolated, AV-blocked rabbit hearts.British journal of pharmacology · 2009Article
- Variability of action potential duration in pharmacologically induced long QT syndrome type 1.Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference · 2009Article
- Slow delayed rectifier K+ current block by HMR 1556 increases dispersion of repolarization and promotes Torsades de Pointes in rabbit ventricles.British journal of pharmacology · 2008Article
- Adrenaline reveals the torsadogenic effect of combined blockade of potassium channels in anaesthetized guinea pigs.British journal of pharmacology · 2008Article
- Importance of vagally mediated bradycardia for the induction of torsade de pointes in an in vivo model.British journal of pharmacology · 2008Article
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4 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
background and purposeTorsade de pointes (TdP) can be induced by a reduction in cardiac repolarizing capacity. The aim of this study was to assess whether IKs blockade or enhancement of INa could potentiate TdP induced by IKr blockade and to investigate whether short-term variability (STV) or triangulation of action potentials preceded TdP. EXPERIMENTAL APPROACH: Experiments were performed in open-chest, pentobarbital-anaesthetized, alpha 1-adrenoceptor-stimulated, male New Zealand White rabbits, which received three consecutive i.v. infusions of either the IKr blocker E-4031 (1, 3 and 10 nmol kg(-1) min(-1)), the IKs blocker HMR1556 (25, 75 and 250 nmol kg(-1) min(-1)) or E-4031 and HMR1556 combined. In a second study rabbits received either the same doses of E-4031, the INa enhancer, ATX-II (0.4, 1.2 and 4.0 nmol kg(-1)) or both of these drugs. ECGs and epicardial monophasic action potentials were recorded. KEY
resultsHMR1556 alone did not cause TdP but increased E-4031-induced TdP from 25 to 80%. ATX-II alone caused TdP in 38% of rabbits, as did E-4031; 75% of rabbits receiving both drugs had TdP. QT intervals were prolonged by all drugs but the extent of QT prolongation was not related to the occurrence of TdP. No changes in STV were detected and triangulation was only increased after TdP occurred. CONCLUSIONS AND IMPLICATIONS: Giving modulators of ion channels in combination substantially increased TdP but, in this model, neither STV nor triangulation of action potentials could predict TdP.
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