Schoors D F, Reynaert H, Huyghens L, Vanhaelst L, Dupont A G
Department of Pharmacology, Vrije Universiteit Brussel (VUB), Belgium.
Cardiovasc Drugs Ther. 1991 Apr;5(2):489-94. doi: 10.1007/BF03029774.
The effect of verapamil and felodipine on imipramine-induced cardiac toxicity was assessed in anaesthetized rats. Rats received either infusion of saline (n = 13), or non-hypotensive doses of felodipine (n = 36) or verapamil (n = 36) over 40 minutes. In saline-pretreated rats IV bolus injection of imipramine (10 mg/kg) resulted in severe hypotension, bradycardia, electromechanical dissociation, and death within 3 minutes. Rats pretreated with nonhypotensive doses of felodipine (1, 3, 6, and 10 micrograms/kg/min) or verapamil (10, 30, 100, and 300 micrograms/kg/min) survived throughout the experiment, despite an initial fall in blood pressure within the first 5 minutes after imipramine administration. Blood pressure returned to baseline levels within 15 minutes. Intermittent ECG monitoring showed significant prolongation of QRS duration after imipramine in both saline (by 138%) and verapamil-pretreated rats (by 63%), whereas in the rats pretreated with felodipine no prolongation was observed (+3%). We conclude that, in our experimental model, felodipine, more than verapamil, protects against the cardiac effects of imipramine intoxication.
在麻醉大鼠中评估了维拉帕米和非洛地平对丙咪嗪所致心脏毒性的影响。大鼠在40分钟内接受生理盐水输注（n = 13），或非低血压剂量的非洛地平（n = 36）或维拉帕米（n = 36）。在生理盐水预处理的大鼠中，静脉推注丙咪嗪（10 mg/kg）导致严重低血压、心动过缓、电机械分离，并在3分钟内死亡。用非低血压剂量的非洛地平（1、3、6和10微克/千克/分钟）或维拉帕米（10、30、100和300微克/千克/分钟）预处理的大鼠在整个实验过程中存活，尽管在给予丙咪嗪后的前5分钟内血压最初有所下降。血压在15分钟内恢复到基线水平。间歇性心电图监测显示，在生理盐水预处理的大鼠（延长138%）和维拉帕米预处理的大鼠（延长63%）中，丙咪嗪给药后QRS波时限均显著延长，而在非洛地平预处理的大鼠中未观察到延长（延长3%）。我们得出结论，在我们的实验模型中，非洛地平比维拉帕米更能预防丙咪嗪中毒的心脏效应。
