Prolongation of QT interval in isolated feline hearts by antipsychotic drugs

Some antipsychotic drugs have been found to prolong the QT interval on elec trocardiographic (ECG) recordings, a phenomenon which, when severe, may fac ilitate the occurrence of complex ventricular arrhythmias such as torsade d e pointes. However, the effects of these drugs on the cardiac repolarizatio n process have not been evaluated extensively. This study was designed to e xamine the potency of five antipsychotic drugs in lengthening the QT interv al of the perfused feline heart: haloperidol, risperidone, sertindole, cloz apine, and olanzapine. The hearts were infused with increasing concentratio ns of drugs (0.1-20 mu mol/L) for 40-minute intervals at each concentration . ECG recordings were made, with signals amplified and data recorded on a s trip chart recorder. Four representative beats from each set of three signa l recordings were chosen for QT interval measurement. Our data indicated th at all tested drugs prolonged the QT interval in a concentration-dependent manner (p < 0.01). Haloperidol and risperidone were significantly more pote nt than sertindole, clozapine, and olanzapine (p < 0.001). At a concentrati on of 0.5 mu mol/L over a 40-minute infusion interval, haloperidol lengthen ed the interval by 26.2 +/- 0.7%, risperidone by 19.4 +/- 2.2%, and sertind ole by 8.9 +/- 3.5% (p < 0.05 compared with baseline); clozapine and olanza pine were less potent. Although species differences may Limit extrapolation of our findings to humans, the cardiac potassium channels of felines clear ly resemble those of humans. This model may serve as the basis for further studies of drug-induced prolongation of the QT interval and precipitation o f ventricular arrhythmias.