摘要
目的 研究治疗量的三氧化二砷 (As2 O3 )对心脏的毒性。方法 通过对 2 8例急性早幼粒细胞白血病 (APL)患者临床症状、基础心率、心电图的动态观察和As2 O3 作用于豚鼠单个心肌细胞后 ,动作电位、L 型钙电流 (ICa L)、外向整流钾电流 (Ik)的即刻变化 ,分析静脉滴入As2 O3 引起心脏毒性的可能机制。结果 2 8例APL患者中 ,有 71 4 %的患者产生不同程度的心脏毒性反应 ,表现为心率加快和心电图上QT间期 (QTc)延长。膜片钳显示As2 O3 1μmol/L使豚鼠心肌细胞 90 %动作电位时程从 (5 6 3 0± 5 5 8)ms延长至 (737 7± 131 7)ms(P <0 0 5 )。使ICa L和Ik 增加。结论 As2 O3 可使部分APL患者出现心动过速和QTc延长 ,并随治疗时间的延长逐渐恢复。As2 O3 延长豚鼠心室肌细胞的动作电位时程 ,影响ICa L和Ik 可能是导致QTc延长的原因。
Objective To study the cardiac toxicity of arsenic trioxide(As 2O 3).Methods To investigate and analyze the probable mechanisms of cardiac toxicity of As 2O 3 by dynamic monitoring of clinical manifestations, basal cardiac rate and electrocardiographic data of acute promyelocyte leukemia (APL) patients during As 2O 3 therapy. The instant change of the action potential , the I Ca-L and I k of single cardiac myocyte of guinea pig was also observed with patch clamp dynamically. Results Approximately 71.4% of the 28 cases of APL showed cardiac toxic reaction in different degree in the first week after As 2O 3 intravenous infusion in general dose, mainly expressing rapid heart rate or prolonged QT interval. As 2O 3 could prolong the action potential duration from (563.0±55.8) ms to (737.7±131.7) ms(P<0.05)and increased the I Ca-L and I k of single cardiac myocyte of guinea pig in vitro. Conclusion As 2O 3 intravenous infusion in general therapeutic dose can cause tachycardia and prolong QT interval in some of the APL patients. The probable mechanism of these side-effects may be due to instant involvement of ionic channel of cardiac myocyte.
出处
《中华内科杂志》
CAS
CSCD
北大核心
2003年第11期785-788,共4页
Chinese Journal of Internal Medicine
基金
黑龙江省留学归国基金资助项目 (LC0 2C14 )
