Effects of denudatine on experimental arrhythmia and heart function (author's
Abstract
Denudatine (Den) is the major alkaloid isolated from Aconitum jinyangense. The iv LD50 of Den and aconitine in mice were 128 and 0.19 mg/kg, respectively. The ig LD50 of Den in mice was 290 mg/kg. After iv injection of Den a dose-dependent bradycardia was observed in rats. Bradycardia was also seen when Den was given ig to rats. The bradycardia induced by Den was neither due to stimulation of the vagus nerve nor due to blockade ofβ-adrenoreceptor.
In anesthetized dogs iv Den 2.5 mg/kg produced a decrease in HR, MAP, LVSP, LV dP/dtmax, CBF and TPR. But 1 mg/kg caused no alternation of these parameters except HR, which decreased only slightly but significantly.
The arrhythmia elicited by aconitine (3μg/kg, iv) in rats was suppressed by Den (25 nig/kg, iv). The antiarrhythmic potency of Den was equivalent to that of quinidine, but weaker than that of diphenylhydantoin (DPH). The aconitine-induced dysrhythmias in rats were completely prevented or inhibited by prior treatment with Den (25, 50 mg/kg iv or 50, 100 mg/kg ig). This action of Den was more marked than that of quinidine and DPH. Pretreatment of rats with Den (26 mg/kg, iv) increased the survival rate of the rats given CaCl2 (25 mg/kg, iv) from 14% up to 75%. As for those rats died eventually both the onset of arrhythmia and the subsequent death were delayed significantly.
Keywords:
In anesthetized dogs iv Den 2.5 mg/kg produced a decrease in HR, MAP, LVSP, LV dP/dtmax, CBF and TPR. But 1 mg/kg caused no alternation of these parameters except HR, which decreased only slightly but significantly.
The arrhythmia elicited by aconitine (3μg/kg, iv) in rats was suppressed by Den (25 nig/kg, iv). The antiarrhythmic potency of Den was equivalent to that of quinidine, but weaker than that of diphenylhydantoin (DPH). The aconitine-induced dysrhythmias in rats were completely prevented or inhibited by prior treatment with Den (25, 50 mg/kg iv or 50, 100 mg/kg ig). This action of Den was more marked than that of quinidine and DPH. Pretreatment of rats with Den (26 mg/kg, iv) increased the survival rate of the rats given CaCl2 (25 mg/kg, iv) from 14% up to 75%. As for those rats died eventually both the onset of arrhythmia and the subsequent death were delayed significantly.