dc.subject | Although parenteral administration of
As2O3 is highly effective in the treatment of
acute promyelocytic leukemia, cardiac
toxicity has been reported. This study
employed Langendorff- perfusion to
determine the direct effects of As2O3 in the
electrophysiological properties of rabbit
hearts after acute or chronic As2O3 treatment
(0.2 mg/Kg/day intravenous for 30 days).
Tissue accumulations of arsenicals,
pathological changes as well as the
reversibility of chronic As2O3 effects were
assessed. We found that cardiac conduction
and repolarization were not altered
whatsoever after acute As2O3 treatment at
clinically relevant (1, 3, 10 μM) and higher
(30 μM) doses. Nevertheless, an extremely
high concentration of As2O3 (300μM)
prolonged the corrected QT interval.
Subsequent to chronic As2O3 administration
and with 30 μM As2O3 via Langendorff
perfusion, polymorphic ventricular
tachycardia was observed (1/7, 14%).
Corrected QT interval was prolonged, while
basic cycle length was shortened.
Significant accumulation of arsenicals in the
cardiac tissue was found, but without any
pathological changes. After As2O3 was
discontinued for 30 days, the chronic As2O3
-induced electrophysiological changes
improved, no ventricular arrhythmia was
noted, and the tissue concentration of
arsenicals decreased considerably. We
therefore conclude that although no
immediate cardiac effects were discernable at
clinically relevant doses, an extremely high
concentration of As2O3 could prolong
ventricular repolarization. Chronic As2O3
treatment resulted in a prolonged ventricular
repolarization, in association with arsenicals
accumulation and with risk of ventricular
tachycardia. These chronic cardiac
toxicities and the tissue accumulation of
arsenicals were, however, partially reversible
after cessation of As2O3. | en |