Effect of E-4031, a new class III antiarrhythmic drug, on reentrant ventricular arrhythmias: comparison with conventional class I drugs.

Abstract

We evaluated the antiarrhythmic efficacy of E-4031, a new class III drug, and compared it with that of conventional class I and II antiarrhythmic agents in terms of electrophysiological actions on refractoriness and conduction in a 7-day-old canine model of myocardial infarction. Sustained monomorphic VT was reproducibly induced in 26 dogs by a premature stimulation method from the right ventricle. Class I drugs (disopyramide, aprindine, flecainide) prevented VT induction in 5 of 13 dogs, and propranolol and E-4031 prevented it in 6 of 6 and 6 of 7 dogs, respectively. The effective refractory period (ERP) was determined at 47 epicardial sites overlying the infarct in each experiment by a S1S2 method. The standard deviation (SD) of the mean ERP of these sites was used as an index of ERP dispersion. The extent of ERP prolongation produced by class I drugs and E-4031 was significantly more marked than that produced by propranolol. However, the SD was increased by class I drugs and E-4031, but not by propranolol. Class I drugs increased the ERP dispersion mainly by an effect on the transmural infarct zone in which the control ERP was more prolonged than in the normal zone. E-4031 tended to prolong the ERP in both the normal and infarct zones, and had a minimal tendency to increase ERP dispersion. In contrast, propranolol decreased the ERP dispersion between zones. Conduction velocity calculated by epicardial mapping was significantly decreased by flecainide, but not by E-4031. We conclude that the antiarrhythmic effect of E-4031 depends largely on its ability to prolong refractoriness without suppressing conduction.(ABSTRACT TRUNCATED AT 250 WORDS)

• Authors: S Ogawa, H Mitamura, H Katoh
• Journal: Cardiovascular drugs and therapy (Cardiovasc Drugs Ther) Vol. 7 Suppl 3 Pg. 621-6 (Aug 1993) ISSN: 0920-3206 [Print] United States
• PMID: 8251432 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Anti-Arrhythmia Agents
• Piperidines
• Potassium Channel Blockers
• Pyridines
• E 4031
• Aprindine
• Disopyramide
• Flecainide

Topics

• Animals
• Anti-Arrhythmia Agents (pharmacology)
• Aprindine (pharmacology)
• Arrhythmias, Cardiac (drug therapy)
• Disease Models, Animal
• Disopyramide (pharmacology)
• Dogs
• Electrophysiology
• Flecainide (pharmacology)
• Myocardial Infarction (drug therapy, physiopathology)
• Piperidines (pharmacology)
• Potassium Channel Blockers
• Pyridines (pharmacology)
• Tachycardia, Ventricular (drug therapy)