低血钾家兔模型中洋地黄心脏毒性的观察

Observation the Alteration of Digitalis Cardiac Toxicity on Hypokalemia Rabbit

目的:制备快速稳定的低血钾家兔模型,在低钾模型上观察洋地黄心脏毒性变化。方法:确定给药剂量、药物浓度等实验条件后,通过肌内注射速尿合并静脉给予胰岛素-葡萄糖混合溶液,制备家兔低钾血症模型,在此基础上,采用去乙酰毛花苷(西地兰)静脉推注诱发家兔心律失常,在正常和低钾血症家兔上比较西地兰诱发心律失常作用。结果:家兔肌肉注射速尿(10mg/kg)30~60min,静脉推注胰岛素-葡萄糖混合溶液(20ml葡萄糖注射液和2U胰岛素,10ml/kg),可以引起家兔低钾血症,在此模型上,家兔采用首次400μg/kg西地兰推注,5min后加推200μg/kg西地兰,可以在20min之内诱发室性心律失常。与正常家兔相比,低钾家兔对西地兰更敏感,诱发心律失常的平均剂量分别为467mg/kg(低钾)和733mg/kg(正常)(P=0.003)。结论:通过实验条件选优,制备了快速稳定的低钾血症模型,可用于观察洋地黄在疾病状态下对心脏的作用。实验方法操作简单,重现性好,可用于临床药理学实验教学。

Objective：To explore the method establishing a rapid and stable hypokalemia rabbit model,observe the alteration of digitalis cardiac toxicity in rabbits with hypokalemia.Methods：Firstly,we selected effective doses of furosemide and mixture of glucose and insulin,administrated by injection to induce hypokalemia.The rabbits in control group were given the same dosage of saline by the same time.Based on this model,deslanoside（200μg/kg,first dose doubling）was administered by intravenous injection to observe the change of electrocardiogram compared with normal condition.Results：Compared with control group,after injection with furosemide and Insulin/Glucose mixture,blood potassium was significantly decreased,ECGⅡ showed typical change of hypokalemia.In addition,a lower dose of digitalis can cause severe arrhythmias（7.33 ml and 4.67 ml respectively,P=0.003）.Conclusion：The results indicated that the usage of furosemide（10 mg/kg）by intramuscular injection combined with Insulin/Glucose mixture（20 ml glucose mixed with 2 Uinsulin）by intravenous injection,could establish a rabbit hypokalemia model,which can be used to observe digitalis cardiac toxicity.The method is safe and feasible.