Johnson G L, Ehrreich S J, el-Hage A N, Balazs T
Res Commun Chem Pathol Pharmacol. 1986 Mar;51(3):351-64.
Heavy male Sprague-Dawley rats die of ventricular fibrillation within 2 to 3 h after isoproterenol administration. Thus, the isoproteronol-treated heavy rat would be a useful model for screening drugs that may prevent sudden cardiac death. Isoproterenol (1 mg/kg s.c.) caused ventricular fibrillation in 79% of 121 vehicle-pretreated heavy rats (greater than 500 g); 82% of the fibrillating rats died, but the remaining 18% spontaneously reverted and survived. A protecting agent should increase the number of survivors by reducing the incidence of ventricular fibrillation and/or by increasing the incidence of spontaneous reversions. Pretreatment (i.p.) with quinidine (40 mg/kg), procainamide (40 mg/kg), phenytoin (40 mg/kg), clofilium (5 mg/kg), verapamil (10 mg/kg), or propranolol (10 mg/kg) reduced the incidence of isoproterenol-induced ventricular fibrillation and death; bretylium (10 mg/kg) and nicotinic acid (100 mg/kg) had no effect. A lower dose of propranolol (2.5 mg/kg) or clofilium (1.5 mg/kg) but not quinidine (10 mg/kg), procainamide (10 mg/kg), or phenytoin (10 mg/kg) also reduced the incidence of ventricular fibrillation. Only clofilium tended to increase the incidence of spontaneous reversions.
体重较重的雄性斯普拉格-道利大鼠在给予异丙肾上腺素后2至3小时内死于心室颤动。因此，用异丙肾上腺素处理的体重较重的大鼠将成为筛选可能预防心脏性猝死药物的有用模型。异丙肾上腺素（1毫克/千克，皮下注射）可使121只经赋形剂预处理的体重较重的大鼠（大于500克）中有79%发生心室颤动；82%发生颤动的大鼠死亡，但其余18%会自发恢复并存活。一种保护剂应通过降低心室颤动的发生率和/或增加自发恢复的发生率来增加存活者的数量。用奎尼丁（40毫克/千克）、普鲁卡因胺（40毫克/千克）、苯妥英（40毫克/千克）、氯非铵（5毫克/千克）、维拉帕米（10毫克/千克）或普萘洛尔（10毫克/千克）进行预处理（腹腔注射）可降低异丙肾上腺素诱发的心室颤动和死亡的发生率；溴苄铵（10毫克/千克）和烟酸（100毫克/千克）则无作用。较低剂量的普萘洛尔（2.5毫克/千克）或氯非铵（1.5毫克/千克）而非奎尼丁（10毫克/千克）、普鲁卡因胺（10毫克/千克）或苯妥英（10毫克/千克）也可降低心室颤动的发生率。只有氯非铵倾向于增加自发恢复的发生率。
