Effect of E-4031, a new class III antiarrhythmic drug, on reentrant ventricular arrhythmias: comparison with conventional class I drugs.
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)
Ogawa
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S
Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
Mitamura
H
H
Katoh
H
H
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001073:Aprindine / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000188:drug therapy*; D004195:Disease Models, Animal; D004206:Disopyramide / Q000494:pharmacology; D004285:Dogs; D004594:Electrophysiology; D005424:Flecainide / Q000494:pharmacology; D009203:Myocardial Infarction / Q000188:drug therapy / Q000503:physiopathology; D010880:Piperidines / Q000494:pharmacology*; D026902:Potassium Channel Blockers; D011725:Pyridines / Q000494:pharmacology*; D017180:Tachycardia, Ventricular / Q000188:drug therapy
D000889:Anti-Arrhythmia Agents; D010880:Piperidines; D026902:Potassium Channel Blockers; D011725:Pyridines; C063968:E 4031; D001073:Aprindine; D004206:Disopyramide; D005424:Flecainide