Hanaki Y, Sugiyama S, Hieda N, Taki K, Hayashi H, Ozawa T
Department of Internal Medicine, Faculty of Medicine, University of Nagoya, Japan.
J Am Coll Cardiol. 1989 Jul;14(1):219-24. doi: 10.1016/0735-1097(89)90077-6.
This study was designed to clarify the cardioprotective effects of various class I antiarrhythmic drugs, i.e., aprindine, disopyramide, flecainide, lidocaine, mexiletine, pentisomide and propafenone, on the ischemic heart. Sixty-one adult mongrel dogs were classified into eight groups according to premedication: 1) control group, physiologic saline solution was administered intravenously 25 min before left anterior descending coronary artery ligation; 2) aprindine group, 3 mg/kg body weight of aprindine intravenously; 3) disopyramide group, 2 mg/kg of disopyramide intravenously; 4) flecainide group, 2 mg/kg of flecainide intravenously followed by drip infusion of 100 micrograms/kg per min; 5) lidocaine group, 2 mg/kg of lidocaine intravenously followed by drip infusion of 100 micrograms/kg per min; 6) mexiletine group, 3 mg/kg per min of mexiletine intravenously followed by drip infusion of 15 micrograms/kg per min; 7) pentisomide group, 5 mg/kg intravenously; and 8) propafenone group, 2 mg/kg intravenously. Arterial blood pressure and electrocardiogram were monitored throughout the experiment. Two hours after coronary occlusion, the heart was excised. Myocardial mitochondria were prepared and mitochondrial function (the respiratory control index and the rate of oxygen consumption in state III) was measured polarographically. Fractionation of myocardial tissues was performed and the lysosomal enzyme (N-acetyl-beta-glucosaminidase and beta-glucuronidase) activities among fractions were measured. No significant hemodynamic changes were observed compared with the control group except for those in the disopyramide and flecainide groups; that is, decrease in heart rate without changes in blood pressure compared with the control group was observed. All antiarrhythmic drugs effectively prevented the development of ventricular arrhythmias associated with ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
本研究旨在阐明各类Ⅰ类抗心律失常药物,即阿普林定、丙吡胺、氟卡尼、利多卡因、美西律、喷替索米和普罗帕酮对缺血心脏的心脏保护作用。61只成年杂种犬根据预处理情况分为8组:1)对照组,在左冠状动脉前降支结扎前25分钟静脉注射生理盐水;2)阿普林定组,静脉注射3mg/kg体重的阿普林定;3)丙吡胺组,静脉注射2mg/kg的丙吡胺;4)氟卡尼组,静脉注射2mg/kg的氟卡尼,随后以每分钟100μg/kg的速度滴注;5)利多卡因组,静脉注射2mg/kg的利多卡因,随后以每分钟100μg/kg的速度滴注;6)美西律组,静脉注射每分钟3mg/kg的美西律,随后以每分钟15μg/kg的速度滴注;7)喷替索米组,静脉注射5mg/kg;8)普罗帕酮组,静脉注射2mg/kg。在整个实验过程中监测动脉血压和心电图。冠状动脉闭塞2小时后,取出心脏。制备心肌线粒体并通过极谱法测量线粒体功能(呼吸控制指数和状态Ⅲ下的耗氧率)。进行心肌组织分级分离并测量各分级中溶酶体酶(N-乙酰-β-氨基葡萄糖苷酶和β-葡萄糖醛酸酶)的活性。与对照组相比,除丙吡胺和氟卡尼组外,未观察到明显的血流动力学变化;也就是说,与对照组相比,观察到心率下降而血压无变化。所有抗心律失常药物均有效预防了与缺血相关的室性心律失常的发生。(摘要截短至250字)