靜脈氧化砷治療之心臟毒性研究：發生率、機轉及發生後之可逆性
Date Issued
2003
Date
2003
Author(s)
吳美環
DOI
912314B002128
Abstract
靜脈三氧化砷治療對於急性骨髓前白
血病療效良好，但臨床經驗顯示有可能有
心臟毒性。本研究以分離兔心臟灌流之實
驗模式，探討是否三氧化砷有直接之心臟
毒性，包括其發生率、電生理特性之變化
與不整脈之誘發狀況。
我們發現，三氧化砷於臨床治療濃度
（1，3，10μM）或更高（30μM）之濃度，
並不會影響心電生理特性，但若以極高之
濃度（300μM）（此種濃度只有可能在中
毒下遇到）則QT 間距會延長。此外，我
們另設立長期靜脈三氧化砷治療之動物模
式，實驗兔接受每天0.2mg/kg 之靜脈三氧
化砷，30 天後再行測定。我們發現，接受
長期靜脈三氧化砷治療之實驗，其QT 間
距延長顯著變長，且會誘發心室頻脈（1/7，
14%），組織濃度之檢定亦顯示砷堆積之
現象。但此種砷堆積之現象有可能於停藥
後，部分會再度排出。
Subjects
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.
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.
arsenic trioxide
heart
electrophysiology
Publisher
臺北市：國立臺灣大學醫學院小兒科
Type
report
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