Dose-toxicity Relationship Study for Cardiotonic Effect of Aconitine

ZHANG Shuo-feng; WU Jin-ying; JIA Zhan-hong; SUN Jian-ning

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Dose-toxicity Relationship Study for Cardiotonic Effect of Aconitine

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- Dose-toxicity Relationship Study for Cardiotonic Effect of Aconitine
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 18, Issue 19, Pages: 222-225(2012)
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- Published：2012
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ZHANG Shuo-feng, WU Jin-ying, JIA Zhan-hong, et al. Dose-toxicity Relationship Study for Cardiotonic Effect of Aconitine[J]. Chinese journal of experimental traditional medical formulae, 2012, 18(19): 222-225.
DOI：

ZHANG Shuo-feng, WU Jin-ying, JIA Zhan-hong, et al. Dose-toxicity Relationship Study for Cardiotonic Effect of Aconitine[J]. Chinese journal of experimental traditional medical formulae, 2012, 18(19): 222-225. DOI：

摘要

目的:动态观察乌头碱的心脏毒性与强心作用。并计算其毒理学参数与药效学参数

评价其使用的安全性

为其临床应用提供实验依据。方法:以大鼠Ⅱ导联心电图变化为指标

经大鼠股静脉缓慢恒速推注乌头碱

连续观察大鼠心电图变化

动态观察乌头碱对心脏毒性的量-毒关系;选用钙离子拮抗剂尼莫地平复制大鼠心衰模型

经大鼠股静脉缓慢恒速推注乌头碱

以心率、左心室内压最大上升速率(+dp/dtmax)和反映心脏做功的指标率压积(RPP)为指标

动态观察乌头碱的强心作用。结果:以RPP

+dp/dtmax为指标计算乌头碱的50%最大效应量(ED50)

以室性早搏(PVC)

停搏(CA)为指标计算乌头碱的半数中毒量(TD50)、半数致死量(LD50)

则乌头碱的治疗指数(TI

按RPP计算)分别为1.84

17.22

TI(按+dp/dtmax计算)分别为1.23

11.54。结论:乌头碱具有强心作用

但也具有心脏毒性

安全范围狭窄。

Abstract

Objective:To analyze the relationship between toxicity and cardiotonic effect of aconitine

calculating the therapeutic index (TI) of aconitine. Method:Regarding rat's electrocardiogram (ECG) change as the index

the toxicity to heart induced by aconitine was studied. Nimodipine

one of Ca2+ antagonist

was used to make heart failure model in rats. The aconitine was injected through femoral vein continuously. The effect on heart rate

+dp/dtmax

LVDP-rate pressure product(RPP) was observed. Result:Regarding RPP or +dp/dtmax as the index of ED50 and regarding PVC or CA as the index of TD50 or LD50

LD50/ED50 or TD50/ED50 was used to calculate the therapeutic index (TI) of aconitine

TI(RPP)were 1.84

17.22 and TI(+dp/dtmax)were 1.23

11.54 respectively. Conclution:Aconitine has cardiotonic effect but has toxicity to heart. TI is small.

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