Antifibrillatory properties of alinidine after coronary artery occlusion in rats.

Ligation of the left anterior descending coronary artery was performed in open-chest anaesthetized rats and mortality as well as changes in ECG were evaluated for 30 min thereafter. Saline or drugs were administered 15 min prior to ligation. In the control group, following a 4 min lag period ventricular arrhythmias as single ectopic beats, ventricular tachycardia and ventricular fibrillation (VF) appeared, reaching a maximum between 10 and 20 min and disappearing after 30 min. Mortality (40% in the control group) coincided with the period of maximal arrhythmias, with VF more common in animals that died than in those surviving. Alinidine, a drug which reduces sino-atrial rate specifically but has no conventional antiarrhythmic properties, reduced mortality and VF. By means of order statistics the quantity 'risk of death' was used for evaluation of drug effects, considering incidence of death and VF as well as duration of VF. This quantity was reduced in correlation with the dose of alinidine (1-6 mg/kg i.v.) and in correlation with the reduction of heart rate. Mexiletine, an antiarrhythmic drug with membrane-depressant properties, also reduced the 'risk of death' dose dependently (1-10 mg/kg i.v.), but there was no correlation with a decrease in heart rate. It is suggested that alinidine reduced 'risk of death' by means of a reduced oxygen demand due to a decrease in heart rate.