莲心总碱及其甲基化物对牵张性心律失常的拮抗效应(英文)

Antagonistic effects of total alkaloids of Lianzixin and their methyl-derivative on stretch-induced arrhythmia

目的 澄清莲心总碱 (TAL)与氨基糖苷类抗生素的共同化学结构带正电的氨基是否使之具有抗牵张性心律失常的共同效应。方法 通过膨胀心室腔内的球囊、夹闭升主动脉和牵拉乳头肌建立心律失常、动作电位时程的缩短和触发活动的模型。采用离体心电图、细胞内微电极和在体单相动作电位的标准技术进行记录。结果 ①TAL和甲基莲心总碱 (TMAL) (2 .5 ,5和 10 μmol·L- 1)能剂量依赖性的缩短大鼠离体心脏牵张性心律失常的持续时间 ,从对照组的 (2 .16± 0 .38)s减少到 (1.5 3± 0 .14 ) ,(0 .93± 0 .2 1) ,(0 .5 2± 0 .35 )s (TAL )和(1.5 9± 0 .16 ) ,(0 .94± 0 .2 1) ,(0 .79± 0 .15 )s(TMAL)。②在麻醉豚鼠 ,TAL 2 .3mg·kg- 1iv和TMAL 2 .6mg·kg- 1iv能显著抑制夹闭主动脉引起的单相动作电位 5 0 %和 90 %复极时程的缩短及触发活动的发生率 ,分别从 (2 8.9± 8.1) %减少到(5 .4± 1.2 ) %和 (10 .8± 2 .3) %。③TAL和TMAL也能显著抑制牵拉豚鼠乳头肌所致的动作电位 5 0 %和 90 %复极时程的缩短。结论 TAL和TMAL能抑制牵张性心律失常和牵张引起的动作电位的改变 ,这种作用可能是通过阻断牵张活化的离子通道实现的。

AIM To clarify whether the common chemical s tructure-the positive-charged amino groups of total alkaloids of Lianzixin(TAL ) and aminoglycosides antibiotics renders them possessing common antagonistic ef fects on stretch-induced arrhythmia. METHODS The kind of arrhythmi a, shortening of action potential duration(APD) and triggered activity(TA) mode ls were established by inflating the intracavitary balloon, clamping the ascendi ng aorta and by stretching ventricular papillary muscle, transiently. Standard t echniques of electrocardiogram(ECG), monophasic action potential(MAP) and intr acellular microelectrode recording were used in vivo and in vi tro. RESULTS ①TAL and total methyl alkaloids of Lianzixin(TM AL) 2.5, 5 and 10 μmol·L -1 concentration-dependently reduced the pers istent duration of stretch-induced arrhythmia in isolated rat hearts from (2. 16±0.38)s to (1.53±0.14), (0.93±0.21), (0.52±0.35)s (TAL), and (1.59± 0.16), (0.94±0.21), (0.79±0.15)s (TMAL ), respectively. ②In anesthetized guinea pigs, TAL 2.3 mg·kg -1 and TMAL 2.6 mg·kg -1, iv, significantly counteracted the shortening of 50% and 90 % monophasic action potential duration evoked by clamping ascending aorta an d declin ed the ratio of triggered activities TA from (28.9±8.1)% to (5.4±1.2)% and (1 0.8±2.3)%, respectively. ③Moreover, TAL 10 μmol·L -1 and TMAL 10 μmol ·L -1 also remar- kably inhibited the shortening of APD 50 and APD 9 0 evoked by stretching in isolated guinea pig papillary muscles. CONCLUS ION TAL and TMAL can suppress the stretch-induced arrhythmia and antagon ize the shortening of APD, which may be related to blockade of stretch-activate d ion channels.