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 ven tricular fibrillation threshold (VFT) induced by electrical stimulatio n directly on the myocardium in anesthetized, open-chest guinea pigs. VFT was assessed by determining the intensity (mA) of electrical curre nt required to induce ventricular fibrillation (VF) and is expressed a s a percentage change of the baseline premedication value. The followi ng antiarrhythmic agents or their solvent were administered intravenou sly (i.v.) to pentobarbital-anesthetized animals (n = 6-12 per group): class I antiarrhythmic agent encainide (1.5 mg/kg); class II antiarrh ythmic agents atenolol (2.5 mg/kg), metoprolol(2.5 mg/kg), and nebivol ol (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 compou nds or their solvents resulted in the following changes in the VFT at 15 min after treatment: saline control, 1 +/- 14% (mean a SEM) from it s 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); ne bivolol, 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); t erikalant, 487 +/- 183% (p < 0.05 vs. saline), and verapamil, -17 +/- 21% (p > 0.05 vs, saline). At the doses used, all compounds significan tly reduced heart rate (HR). The class I antiarrhythmic agent encainid e and the class III antiarrhythmic agents DL-sotalol, dofetilide, and terikalant significantly prolonged the ventricular repolarization (QT- and QTc-intervals), whereas only encainide significantly increased co nduction time (QRS duration). These results indicate that class III an tiarrhythmic agents have the most potent antifibrillatory action in th e model of VFT of anesthetized guinea pigs.