Comparison of the Cardiac Electrophysiological Effects of Flecainide and Hydroquinidine in Anesthetized Dog

Chézalviel, F.; Weissenburger, J; Ertzbischoff, O; Jm, Poirier; Harlé, X; Jm, Davy; Biour, M; Cheymol, G

doi:10.1097/00005344-199001000-00008

Journal of Cardiovascular Pharmacology

1990

DOI: 10.1097/00005344-199001000-00008

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Comparison of the Cardiac Electrophysiological Effects of Flecainide and Hydroquinidine in Anesthetized Dog

F. Chézalviel¹,

J Weissenburger²,

O Ertzbischoff³

et al.

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Validation of visualized transgenic zebrafish as a high throughput model to assay bradycardia related cardio toxicity risk candidates

Wen

Liu

Chen³

et al. 2012

J of Applied Toxicology

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Drug-induced QT prolongation usually leads to torsade de pointes (TdP), thus for drugs in the early phase of development this risk should be evaluated. In the present study, we demonstrated a visualized transgenic zebrafish as an in vivo high-throughput model to assay the risk of drug-induced QT prolongation. Zebrafish larvae 48 h post-fertilization expressing green fluorescent protein in myocardium were incubated with compounds reported to induce QT prolongation or block the human ether-a-go-go-related gene (hERG) K⁺ current. The compounds sotalol, indapaminde, erythromycin, ofoxacin, levofloxacin, sparfloxacin and roxithromycin were additionally administrated by microinjection into the larvae yolk sac. The ventricle heart rate was recorded using the automatic monitoring system after incubation or microinjection. As a result, 14 out of 16 compounds inducing dog QT prolongation caused bradycardia in zebrafish. A similar result was observed with 21 out of 26 compounds which block hERG current. Among the 30 compounds which induced human QT prolongation, 25 caused bradycardia in this model. Thus, the risk of compounds causing bradycardia in this transgenic zebrafish correlated with that causing QT prolongation and hERG K⁺ current blockage in established models. The tendency that high logP values lead to high risk of QT prolongation in this model was indicated, and non-sensitivity of this model to antibacterial agents was revealed. These data suggest application of this transgenic zebrafish as a high-throughput model to screen QT prolongation-related cardio toxicity of the drug candidates.

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Validation of visualized transgenic zebrafish as a high throughput model to assay bradycardia related cardio toxicity risk candidates

Wen

Liu

Chen³

et al. 2012

J of Applied Toxicology

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Effects of flecainide on the rate dependence of atrial refractoriness, atrial repolarization and atrioventricular node conduction in anesthetized dogs

O’Hara

Villemaire

Talajic

et al. 1992

Journal of the American College of Cardiology

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Effects of Flecainide, Encainide, and Clofilium on Ventricular Refractory Period Extension by Transcardiac Shocks

Sweeney

Gill

Steinberg

et al. 1996

Pacing Clinical Electrophis

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Comparison of the Cardiac Electrophysiological Effects of Flecainide and Hydroquinidine in Anesthetized Dog

Cited by 3 publications

References 0 publications

Validation of visualized transgenic zebrafish as a high throughput model to assay bradycardia related cardio toxicity risk candidates

Validation of visualized transgenic zebrafish as a high throughput model to assay bradycardia related cardio toxicity risk candidates

Effects of flecainide on the rate dependence of atrial refractoriness, atrial repolarization and atrioventricular node conduction in anesthetized dogs

Effects of Flecainide, Encainide, and Clofilium on Ventricular Refractory Period Extension by Transcardiac Shocks

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