https://scholars.lib.ntu.edu.tw/handle/123456789/194440| Title: | 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 | Authors: | 吳美環 | Keywords: | 三氧化砷;心臟電生理學;不整脈;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.;arsenic trioxide;heart;electrophysiology | Issue Date: | 2003 | Publisher: | 臺北市：國立臺灣大學醫學院小兒科 | 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。 |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/22877 | Other Identifiers: | 912314B002128 | Rights: | 國立臺灣大學醫學院小兒科 |
| Appears in Collections: | 醫學系 |
| File | Description | Size | Format | |
|---|---|---|---|---|
| 912314B002128.pdf | 41.63 kB | Adobe PDF | View/Open |
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