Prolongation of cardiac repolarization by arsenic trioxide

Arsenic trioxide (As2O3; ATO) has recently been found to be very effective for relapsed acute promyelocytic leukemia. Several articles reported prolongation of QT interval or ventricular arrhythmias in patients receiving ATO. However, the QT-prolonging effect has not been confirmed and the direct membrane effect of ATO has never been studied. In the present investigation, using conventional action potential recording technique, we found that ATO dose dependently prolonged action potential duration (APD) in guinea pig papillary muscle with a slow pacing frequency. Parenteral administration of ATO prolonged QT interval and APD in guinea pig hearts. Intravenous infusion of clinically relevant doses of ATO prolonged QT interval and APD dose dependently. These studies suggest that ATO has a direct effect on cardiac repolarization. Patients who are receiving ATO should avoid concomitant administration of other QT-prolonging agents or conditions in favor of delaying cardiac repolarization.