ArticleBritish journal of pharmacology2008
Importance of vagally mediated bradycardia for the induction of torsade de pointes in an in vivo model.
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 17 papers.
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Who cites it
17 citing papers in PubMed, 40 citations in OpenAlex.
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- Long-Term Endurance Exercise Training Alters Repolarization in a New Rabbit Athlete's Heart Model.Frontiers in physiology · 2021Article
- Symptomatic Premature Ventricular Contractions in Vasovagal Syncope Patients: Autonomic Modulation and Catheter Ablation.Frontiers in physiology · 2021Article
- Inter-individual variability and modeling of electrical activity: a possible new approach to explore cardiac safety?Scientific reports · 2016Article
- The high frequency relationship: implications for torsadogenic hERG blockers.British journal of pharmacology · 2016Article
- Role of autonomic reflex arcs in cardiovascular responses to air pollution exposure.Cardiovascular toxicology · 2015Review
- Autonomic involvement in idiopathic premature ventricular contractions.Clinical research in cardiology : official journal of the German Cardiac Society · 2013Article
- Overt and latent cardiac effects of ozone inhalation in rats: evidence for autonomic modulation and increased myocardial vulnerability.Environmental health perspectives · 2012Article
- Cardiac ventricular repolarization reserve: a principle for understanding drug-related proarrhythmic risk.British journal of pharmacology · 2011Review
- The two-pore domain potassium channel KCNK5: induction by estrogen receptor alpha and role in proliferation of breast cancer cells.Molecular endocrinology (Baltimore, Md.) · 2011Article
- Renal defects in KCNE1 knockout mice are mimicked by chromanol 293B in vivo: identification of a KCNE1-regulated K+ conductance in the proximal tubule.The Journal of physiology · 2011Article
- Biomarkers and endogenous determinants of dofetilide-induced torsades de pointes in α(1) -adrenoceptor-stimulated, anaesthetized rabbits.British journal of pharmacology · 2010Article
- Bradycardia-induced Torsade de Pointes - An arrhythmia Less Understood.Indian pacing and electrophysiology journal · 2010Article
- Minimizing repolarization-related proarrhythmic risk in drug development and clinical practice.Drugs · 2010Review
- And the winner is ... RGS4!Circulation research · 2008Article
- Rabbit models of heart disease.Drug discovery today. Disease models · 2008Review
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
background and purposeBradycardia is a risk factor for the development of torsade de pointes (TdP). The aim of this work was to compare the importance of changes in heart rate and arterial blood pressure in the development of drug-induced TdP and to investigate the role of vagal influences. EXPERIMENTAL APPROACH: Experiments were performed in open-chest, pentobarbital-anaesthetized, male rabbits which were given clofilium (20, 60 and 200 nmol kg(-1) min(-1)) with rising doses of either phenylephrine (75, 150, 225 and 300 nmol kg(-1) min(-1)), angiotensin II (0.25, 0.5, 0.75 and 1 nmol kg(-1) min(-1)) or saline. A fourth group received phenylephrine and cloflium after bilateral vagotomy. ECGs, haemodynamics and epicardial monophasic action potentials were recorded. KEY
resultsTdP occurred in 57% of rabbits given phenylephrine and clofilium. Replacement of phenylephrine with saline or angiotensin II reduced the incidence of TdP to 0 and 17%, respectively. Vagotomy prevented TdP in rabbits given phenylephrine and clofilium. Increases in blood pressure induced by phenylephrine and angiotensin II were similar. Bradycardia only occurred with phenylephrine and was reduced but not abolished by vagotomy. Neither short-term variability of repolarization nor action potential triangulation could predict TdP. CONCLUSIONS AND IMPLICATIONS: These results indicate that reflex activation of vagal nerve activity is essential for the induction of drug-induced TdP in alpha1-adrenoceptor-stimulated anaesthetized rabbits. This implies that alterations in vagal activity may also precipitate episodes of drug-induced TdP in man and that this should be considered in selecting models used in drug development.
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