Abstract: ObjectiveTo study the influences of "dose-toxicity" relationship and "time-toxicity" relationship of cardiotoxicity, through electrocardiogram (ECG) and serum biochemical indexes changes caused by multiple doses Aconite water extract on mice. MethodsMice were grouped according to different time or dose points, and given multiple doses of Aconite water extract by gavage respectively. Changes of ECG were observed. The ratio of heart, liver and kidney to body was measured, the contents of CK and LDH related to cardiotoxicity in serum were detected. ResultsThe "time- toxicity" relationship showed that the heart rate of mice dropped 24 hours later of administration compared with normal group. The duration of P extended and the amplitude enlarged. P-R interval, QRS extended and QT interval reduced. Cardiac index decreased while the contents of CK and LDH increased. All changes of them were more statistically significant 48 hours later. The "dose- toxicity" relationship showed that the heart rate of mice and the contents of CK and LDH in serum elevated. P-R interval, QRS and QT interval extended and the length of QT interval was inversely proportional to heart rate. Cardiac index decreased and there was no significant change of liver index and kidney index among different groups. All changes of them showed a dose dependent manner. ConclusionAconite water extract which is gavaged with a single dose to mice can cause cardiotoxicity and there is a certain relationship of "dose-time-toxicity". However the mechanism of cardiotoxicity will obviously require further investigation.

Key words: Aconitum carmichaeli Debx., cardiotoxicity, "dose-time-toxicity" relationship