Protective effects of felodipine and verapamil against imipramine-induced lethal cardiac conduction disturbances in the anaesthetized rat

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.