Kelliher G J, Roberts J
J Pharmacol Exp Ther. 1976 Apr;197(1):10-8.
The cardiotoxic effect of ouabain was explored in rabbits at different ages. The dose of ouabain necessary to produce ventricular tachycardia and death in 1-to 4-week-old rabbits was significantly greater than that required in older animals. In the 1 to 3-week-old animals, ventricular fibrillation occurred only once whereas in animals older than 3 weeks, fibrillation occurred in 23 of 31 animals. A similar pattern of sensitivity to ouabain was observed in bilaterally vagotomized animals. Neither the initial heart rate nor the potassium content of the ventricles in the different age groups appeared to have any influence on the change in the cardiotoxic dose of ouabain. Heart weight increased during the interval when the occurrence of fibrillation increased but it may not fully explain the alteration in the mode of death since fibrillation occurred in some of the younger animals with bilateral vagotomy before the heart weight increased. The catecholamine content of ventricles from 4-to 12-week-old rabbits was significantly greater than that in 1- or 3-week-old rabbits. The age-dependent decrease in the dose of ouabain necessary to produce ventricular tachycardia, ventricular fibrillation and death appeared to be associated with an increase oof ventricular norepinephrine content, although other factors may also play an important part in this response.
研究了哇巴因对不同年龄家兔的心脏毒性作用。1至4周龄家兔产生室性心动过速和死亡所需的哇巴因剂量显著高于年龄较大的动物。在1至3周龄的动物中,室颤仅发生1次,而在3周龄以上的动物中,31只中有23只发生了室颤。在双侧迷走神经切断的动物中也观察到了对哇巴因的类似敏感性模式。不同年龄组的初始心率和心室钾含量似乎对哇巴因心脏毒性剂量的变化均无影响。在室颤发生率增加的时间段内心脏重量增加,但这可能无法完全解释死亡方式的改变,因为在一些年轻的双侧迷走神经切断动物中,在心脏重量增加之前就发生了室颤。4至12周龄家兔心室的儿茶酚胺含量显著高于1或3周龄家兔。产生室性心动过速、室颤和死亡所需的哇巴因剂量随年龄的降低似乎与心室去甲肾上腺素含量的增加有关,尽管其他因素在这种反应中也可能起重要作用。