Antifibrillary Action of Class I-IV Antiarrhythmic Agents in the Model of Ventricular Fibrillation Threshold of Anesthetized Guinea Pigs

We compared the effects of class I-IV antiarrhythmic agents on the ventricular fibrillation threshold (VFT) induced by electrical stimulation directly on the myocardium in anesthetized, open-chest guinea pigs. VFT was assessed by determining the intensity (mA) of electrical current required to induce ventricular fibrillation (VF) and is expressed as a percentage change of the baseline premedication value. The following antiarrhythmic agents or their solvent were administered intravenously (i.v.) to pentobarbital-anesthetized animals (n = 6-12 per group): class I antiarrhythmic agent encainide (1.5 mg/kg); class II antiarrhythmic agents atenolol (2.5 mg/kg), metoprolol (2.5 mg/kg), and nebivolol (2.5 mg/kg); class III antiarrhythmic agents dofetilide (0.08 mg/kg), terikalant (0.04 mg/kg), and DL-sotalolol (10 mg/kg); and class IV antiarrhythmic agent verapamil (0.16 mg/kg). The antiarrhythmic compounds or their solvents resulted in the following changes in the VFT at 15 min after treatment: saline control, 1 +/- 14% (mean +/- SEM) from its baseline value; 10% hydroxypropyl-beta-cyclodextrine (CD), 4 +/- 13%; encainide, 183 +/- 46% (p < 0.05 vs. saline); atenolol, 66 +/- 23% (p > 0.05 vs. saline); metoprolol, 89 +/- 25% (p > 0.05 vs. saline); nebivolol, 224 +/- 58% (p < 0.05 vs. 10% CD); DL-sotalol, 485 +/- 119% (p < 0.05 vs. saline); dofetilide, 357 +/- 69% (p < 0.05 vs. saline); terikalant, 487 +/- 183% (p < 0.05 vs. saline), and verapamil, -17 +/- 21% (p > 0.05 vs. saline). At the doses used, all compounds significantly reduced heart rate (HR).(ABSTRACT TRUNCATED AT 250 WORDS)