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Prepublished online as a Blood First Edition Paper on May 24, 2002; DOI 10.1182/blood-2002-02-0598.
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Blood, 15 September 2002, Vol. 100, No. 6, pp. 2249-2252
BRIEF REPORT
Prolongation of cardiac repolarization by arsenic
trioxide
Chern-En Chiang,
Hsiang-Ning Luk,
Tsui-Ming Wang, and
Philip Yu-An Ding
From the Division of Cardiology, Taipei Veterans
General Hospital and National Yang-Ming University; Department of
Anesthesiology, Chang-Gung Memorial Hospital; and Graduate Institute of
Medical Science, Taipei Medical University, Taiwan.
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.
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