Assessment of drug effects on spontaneous and induced ventricular arrhythmias in a 24-h canine infarction model.
The antiarrhythmic efficacy of encainide, sotalol, flecainide and disopyramide was evaluated in anesthetized dogs subjected to 2-stage total occlusion of the left anterior descending coronary artery. Utilization of this canine model, while anesthetized, permitted the assessment of drug effects not only on uni- and/or multi-focal ectopic ventricular arrhythmias, but also on dysrhythmias associated with aberrant conduction or reentrant excitation pathways. The former was assessed by quantification of ectopic-to-total beat ratios while the later was determined by subjecting the animal to provocative stimuli which produced repetitive ventricular responses. At the cumulative i.v. doses studied, encainide (0.5-4 mg/kg), flecainide (1-8 mg/kg) and disopyramide (0.3-10 mg/kg), but not sotalol (2-8 mg/kg), effectively suppressed ventricular ectopic activity in a dose-related manner. In contrast, sotalol was highly effective in preventing the induction of reentrant ventricular tachyarrhythmias. Disopyramide was only modestly active, while flecainide and encainide had the least favorable profiles of effect in suppressing re-entry arrhythmias in this model. Based on these observations, the anesthetized Harris dog appears to represent a useful two-faceted in vivo model for use in the evaluation of potential antiarrhythmic agents.
D000813:Anilides / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000209:etiology; D004206:Disopyramide / Q000494:pharmacology; D004285:Dogs; D004562:Electrocardiography; D016700:Encainide; D005260:Female; D005424:Flecainide / Q000494:pharmacology; D008297:Male; D009203:Myocardial Infarction / Q000150:complications*; D013015:Sotalol / Q000494:pharmacology
D000813:Anilides; D000889:Anti-Arrhythmia Agents; D013015:Sotalol; D004206:Disopyramide; D005424:Flecainide; D016700:Encainide