Fiedler V B, Kettenbach B, Göbel H, Nitz R E
Naunyn Schmiedebergs Arch Pharmacol. 1985 Aug;330(2):155-61. doi: 10.1007/BF00499909.
This study was designed to analyze the effects of carbocromene and dipyridamole on the haemodynamic and electrocardiographic side-effects resulting from imipramine infusion in anaesthetised rats and dogs. Imipramine was infused at 1 mg/kg/min until cardiac failure and vascular collapse terminated the experiment at 21 +/- 2.3 min in rats and at 29.5 +/- 2.1 min in dogs. This was characterized by hypotension, bradycardia, intraventricular conduction delay, cardiac tachyarrhythmia and A-V block. Carbocromene (4 mg/kg i.v., followed by 80 micrograms/kg/min) protected the animals against heart failure. This was associated with delayed hypotension and negative inotropy, and lower incidence of heart block. Survival time increased to 37 +/- 1.5 min (P less than 0.05), and 54.2 +/- 2.6 min (P less than 0.02) in rats and dogs, respectively. Dipyridamole (0.5 mg/kg i.v., followed by 80 micrograms/kg/min) failed to decrease imipramine toxicity as judged by the haemodynamic and electrocardiographic parameters and did not alter survival time of imipramine controls. These results suggest that carbocromene is an effective treatment for imipramine-induced cardiovascular collapse and cardiac arrhythmias, the beneficial effects being largely due to metabolic and membrane stabilizing effects. Carbocromene has both therapeutic and prophylactic value and appears to be superior to dipyridamole therapy.
本研究旨在分析卡巴克络和双嘧达莫对麻醉大鼠和犬静脉输注丙咪嗪所产生的血流动力学和心电图副作用的影响。以1mg/kg/min的速度静脉输注丙咪嗪，直至出现心力衰竭和血管虚脱，实验终止，大鼠为21±2.3分钟，犬为29.5±2.1分钟。其特征为低血压、心动过缓、室内传导延迟、心脏快速性心律失常和房室传导阻滞。卡巴克络（静脉注射4mg/kg，随后以80μg/kg/min的速度输注）可保护动物免于心力衰竭。这与低血压延迟出现、负性肌力作用以及心脏传导阻滞发生率降低有关。大鼠和犬的存活时间分别增加至37±1.5分钟（P<0.05）和54.2±2.6分钟（P<0.02）。根据血流动力学和心电图参数判断，双嘧达莫（静脉注射0.5mg/kg，随后以80μg/kg/min的速度输注）未能降低丙咪嗪的毒性，也未改变丙咪嗪对照组的存活时间。这些结果表明，卡巴克络是治疗丙咪嗪所致心血管虚脱和心律失常的有效药物，其有益作用主要归因于代谢和膜稳定作用。卡巴克络具有治疗和预防价值，似乎优于双嘧达莫治疗。
