ArticleBritish journal of pharmacology2008
Adrenaline reveals the torsadogenic effect of combined blockade of potassium channels in anaesthetized guinea pigs.
Article in British journal of pharmacology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 17 citations in OpenAlex.
- hERG epitope mimic-decoy peptide corrects autoimmune-long QT syndrome in guinea pigs.Communications medicine · 2026Article
- Nitrous oxide improves cardiovascular, respiratory, and thermal stability during prolonged isoflurane anesthesia in juvenile guinea pigs.Pharmacology research & perspectives · 2021Article
- Effect of butylphthalide intervention on experimental autoimmune myositis in guinea pigs.Experimental and therapeutic medicine · 2018Article
- 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
- 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
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
background and purposeTorsade de pointes (TdP) can be induced in several species by a reduction in cardiac repolarizing capacity. The aim of this study was to assess whether combined I(Kr) and I(Ks) blockade could induce TdP in anaesthetized guinea pigs and whether short-term variability (STV) or triangulation of action potentials could predict TdP. EXPERIMENTAL APPROACH: Experiments were performed in open-chest, pentobarbital-anaesthetized, adrenaline-stimulated male Dunkin Hartley guinea pigs, which received three consecutive i.v. infusions of either vehicle, the I(Kr) blocker E-4031 (3, 10 and 30 nmol kg(-1) min(-1)), the I(Ks) blocker HMR1556 (75, 250, 750 nmol kg(-1) min(-1)) or E-4031 and HMR1556 combined. Phenylephrine-stimulated guinea pigs were also treated with the K(+) channel blockers in combination. Arterial blood pressure, ECGs and epicardial monophasic action potential (MAP) were recorded. KEY
resultsTdP was observed in 75% of adrenaline-stimulated guinea pigs given the K(+) channel blockers in combination, but was not observed in guinea pigs treated with either I(K) blocker alone, or in phenylephrine-stimulated guinea pigs. Salvos and ventricular tachycardia occurred with adrenaline but not with phenylephrine. No changes in STV or triangulation of the MAP signals were observed before TdP. CONCLUSIONS AND IMPLICATIONS: Combined blockade of both I(Kr) and I(Ks) plus the addition of adrenaline were required to induce TdP in anaesthetized guinea pigs. This suggests that there must be sufficient depletion of repolarization reserve and an appropriate trigger for TdP to occur.
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