Detection of proarrhythmia in the female rabbit heart: blinded validation.

摘要: Introduction: Reliable detection of drug-induced proarrhythmia, especially the potential for polymorphic ventricular tachycardia, is great importance in development new compounds that are safe heart and was evaluated a blinded study. Methods Results: In 142 female rabbits, monophasic action used to determine intraventricular conduction, duration (APD), triangulation (APD30 APD90), reverse use-dependence, instability presence chaotic behavior, early afterdepolarizations, torsades de pointes (TdP), fibrillation. addition, 31 coded drugs were tested fashion another 150 hearts. Prototype cardiovascular agents [quinidine (IA), lidocaine (IB), flecainide (IC), propranolol (II), sotalol (IIIB), amiodarone (IIIAB) verapamil (IV)] correctly characterized terms their effects upon conduction APD. Agents documented clinical practice have proarrhythmic (droperidol, sotalol, mibefradil, bepridil, lidoflazine, ketanserin, sertindole, terfenadine, haloperidol, astemizole, cisapride, ziprasidone, lubeluzole, dofetilide, quinidine, ibutilide) identified as such. Pimozide reported rarely produce TdP also found elicit Class III with few adverse effects. Equally important, believed not be (two solvents, atenolol, propranolol, fenoximone, cetirizine, verapamil, sildenafil, lidocaine, diltiazem) having no activity. Conclusion: The SCREENIT method properly quantified prototype noncardiovascular various mechanisms, but it did false-positive results.(J Cardiovasc Electrophysiol, Vol. 14, pp. 287-294, March 2003)