ArticleBritish journal of pharmacology2009
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.
Article in British journal of pharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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14 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Co-expression of calcium and hERG potassium channels reduces the incidence of proarrhythmic events.Cardiovascular research · 2021Pooled it
- Dihydrotestosterone Pretreatment Diminishes the Severity of Drug-Induced Torsades de Pointes.Journal of cardiovascular pharmacology · 2025Article
- Antiarrhythmic and Inotropic Effects of Selective NaInternational journal of molecular sciences · 2022Review
- Long-Term Endurance Exercise Training Alters Repolarization in a New Rabbit Athlete's Heart Model.Frontiers in physiology · 2021Article
- Chronic intermittent tachypacing by an optogenetic approach induces arrhythmia vulnerability in human engineered heart tissue.Cardiovascular research · 2020Article
- Progesterone pretreatment reduces the incidence of drug-induced torsades de pointes in atrioventricular node-ablated isolated perfused rabbit hearts.Journal of cardiovascular electrophysiology · 2019Article
- BlindedFrontiers in pharmacology · 2019Article
- The anaesthetized rabbit with acute atrioventricular block provides a new model for detecting drug-induced Torsade de Pointes.British journal of pharmacology · 2017Article
- Selective Na(+) /Ca(2+) exchanger inhibition prevents Ca(2+) overload-induced triggered arrhythmias.British journal of pharmacology · 2014Article
- New antiarrhythmic targets to control intracellular calcium handling.Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation · 2014Article
- Absolute beat-to-beat variability and instability parameters of ECG intervals: biomarkers for predicting ischaemia-induced ventricular fibrillation.British journal of pharmacology · 2014Article
- Estradiol promotes sudden cardiac death in transgenic long QT type 2 rabbits while progesterone is protective.Heart rhythm · 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
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeThe Na+/Ca2+ exchanger (NCX) may contribute to triggered activity and transmural dispersion of repolarization, which are substrates of torsades de pointes (TdP) type arrhythmias. This study examined the effects of selective inhibition of the NCX by SEA0400 on the occurrence of dofetilide-induced TdP. EXPERIMENTAL APPROACH: Effects of SEA0400 (1 micromol x L(-1)) on dofetilide-induced TdP was studied in isolated, Langendorff-perfused, atrioventricular (AV)-blocked rabbit hearts. To verify the relevance of the model, lidocaine (30 micromol x L(-1)) and verapamil (750 nmol x L(-1)) were also tested against dofetilide-induced TdP. KEY
resultsAcute AV block caused a chaotic idioventricular rhythm and strikingly increased beat-to-beat variability of the RR and QT intervals. SEA0400 exaggerated the dofetilide-induced increase in the heart rate-corrected QT interval (QTc) and did not reduce the incidence of dofetilide-induced TdP [100% in the SEA0400 + dofetilide group vs. 75% in the dofetilide (100 nmol x L(-1)) control]. In the second set of experiments, verapamil further increased the dofetilide-induced QTc prolongation and neither verapamil nor lidocaine reduced the dofetilide-induced increase in the beat-to-beat variability of the QT interval. However, lidocaine decreased and verapamil prevented the development of dofetilide-induced TdP as compared with the dofetilide control (TdP incidence: 13%, 0% and 88% respectively). CONCLUSIONS AND IMPLICATIONS: Na+/Ca2+ exchanger does not contribute to dofetilide-induced TdP, whereas Na+ and Ca2+ channel activity is involved in TdP genesis in isolated, AV-blocked rabbit hearts. Neither QTc prolongation nor an increase in the beat-to-beat variability of the QT interval is a sufficient prerequisite of TdP genesis in rabbit hearts.
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