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)
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Department of Cardiovascular and Pulmonary Pharmacology, Janssen Research Foundation, Beerse, Belgium.
Remeysen
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De Clerck
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D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001262:Atenolol / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D001578:Benzopyrans / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D002839:Chromans / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004562:Electrocardiography / Q000187:drug effects; D016700:Encainide / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D004983:Ethanolamines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D006329:Heart Conduction System / Q000187:drug effects; D007275:Injections, Intravenous; D008297:Male; D008790:Metoprolol / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000068577:Nebivolol; D010627:Phenethylamines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D013015:Sotalol / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D014693:Ventricular Fibrillation / Q000188:drug therapy*; D014700:Verapamil / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use
D000319:Adrenergic beta-Antagonists; D000889:Anti-Arrhythmia Agents; D001578:Benzopyrans; D002839:Chromans; D004983:Ethanolamines; D010627:Phenethylamines; D010880:Piperidines; D013449:Sulfonamides; D000068577:Nebivolol; D001262:Atenolol; D013015:Sotalol; D014700:Verapamil; C063899:terikalant; D008790:Metoprolol; C063533:dofetilide; D016700:Encainide