Verapamil modulating arsenic trioxide-induced QT interval prolongation in guinea pig  

作　　者：SUN Hong-li,JIAO Jun-dong,CHU Wen-feng,ZHOU Yu-hong,WANG Xiao-hui,YANG Bao-feng ( Department of Pharmacology, Harbin Medical University Bio-pharmaceutical Key Laboratory of Heilongjiang Province-Incubator of State Key Laboratory , Harbin 150086, China) 

出　　处：《哈尔滨医科大学学报》2005年第4期378-378,共1页Journal of Harbin Medical University

摘　　要：Objective To investigate therapeutic action of verapamil on QT prolongation induced by arsenic trioxide (As2O3) in guinea pig and to further explore its possible mechanism. Methods Different doses of As2O3 was infused intravenously to observe the changes of QT interval on the electrocardiogram (ECG) at different times in guinea pig.Patch clamp technique and laser scanning confocal microscopy were utilized to study the action of As2O3 on action potential duration (APD),L-type calcium current (ICa-L), rapid delayed rectifier potassium current (IKr) and intracellular calcium concentration ([Ca2+]i) of guinea pig myocytes. At the same time, verapamil was applied preliminarily to evaluate effects of verapamil on changes of the above index induced by AS2O3 . Results Intravenous administration of As2O3 at the dose of 1.6mg/kg and 0.8mg/kg prolonged QT interval on ECG obviously in guinea pig hearts dose dependently and time de pendently. QTc (corrected QT interval) was progressively prolonged in the 2-hour period of intravenous infusion of 1.6mg/ kg As2O3 from (328 .5±30.9)ms of control to (388 .4±31. 3)ms at 2h following As2O3 (P < 0.01). When verapamil was pretreated for 5min,then 1.6mg/kg As2O3 was added,the results showed that QTc was shorter in verapamil-treatment group (357 .3±21 .4)ms than that in As2O3 group (388 .4±31.3)ms (P<0.05) at 2h.Confocal experiments showed that in normal Tyrode solution, As2O3 (1μmol/L and 10/μmol/L) had no obvious effects on resting [Ca2+ ]i( P > 0 .05) in guinea pig cardiomyoeytes,however, 10μmol/L As2O3 could markedly enhance [Ca2+ ]. increase induced by KCl 60mmol/ L and the peak value increased from 903 .4±369.4 to 1674. 6±563 .2 ( P < 0.05 ) . The action of elevating [ Ca2+ ]i could be blocked by 10μmol/L verapamil incompletely. The patch-clamp studies indicated that As2O3 at concentration of 10μmol/L prolonged APD50 from (263 .6±75 .2)ms to (523.9±47 .8)ms (P<0.01) and APD90 from (277.5±77.5) ms to (536.3±49.6)ms (P<0.01),and increased ICa-L from ( -6.0±1.5)pA/pF Objective To investigate therapeutic action of verapamil on QT prolongation induced by arsenic trioxide （As2O3） in guinea pig and to further explore its possible mechanism. Methods Different doses of As2O3 was infused intravenously to observe the changes of QT interval on the electrocardiogram （ECG） at different times in guinea pig. Patchclamp technique and laser scanning confocal microscopy were utilized to study the action of As2O3 on action potential duration （APD）,

关 键 词：异搏定 冠状动脉扩张药 三氧化砷 QT间期 猪 动物实验 

分 类 号：R972[医药卫生—药品] R-332[医药卫生—药学]