Evaluation of drugs inducing QT-interval prolongation by ECG recorded from the isolated guinea-pig heart perfused with the Langendorff's method

We examined effects of various drugs on ECG recorded from isolated perfused guinea-pig heart, and compared the effects of the drugs on the QT-interval with those on the action potential duration in vitro and ECGs recorded from non-anesthetized guinea-pig. Measurements of ECG were done by placing one electrode on the apex of the heart and the other on the isolated aorta. ECG thus recorded showed the conventional ECG-pattern. Drugs examined were sotalol, terfenadine, imipramine, amiodarone, amitriptyline, haloperidol and erythromycin. Almost of all drugs examined showed QT-interval prolongation at the doses higher than 10-6mol/L. QT-interval prolongation in the ECG recorded from isolated perfused hearts was comparable with prolongation of the action potential induced by these drug in vitro. It is concluded that the method employed in the present experiment detecting the drug-induced QT-prolongation in the isolated perfused heart is reliable, and can be used for screening compounds with potential proarrhythmic properties.