A dual model for cardiac arrhythmias: coexistence of re-entry and abnormal automaticity and effects of antiarrhythmic agents.
1. We have developed a dual model for arrhythmia anaesthetized dogs. The model consists of an inducible re-entrant atrial tachycardia and spontaneous ventricular ectopies in the same heart. 2. The model for re-entrant atrial tachycardia was created by crushing the right atrium longitudinally in the intercaval region and transversely in the front free wall parallel to the atrioventricular groove. Ventricular abnormal automaticity was produced by prior (20 approximately 24 h) left anterior descending coronary artery occlusion. The ventricular arrhythmia was partially suppressed during rapid pacing-induced atrial tachycardia and resumed after atrial re-entry was terminated. 3. Mapping experiments indicate that the atrial tachycardia was due to circus movement occurring in the tissue around the tricuspid ring. This re-entrant circuit was identical to that induced in the model created by the incision method. 4. Clofilium (0.75 mg kg-1, n = 5) increased the cycle length of atrial re-entry by 14 +/- 4% from 139 +/- 12 to 159 +/- 18 ms (P less than 0.05). Flecainide (1.8 +/- 0.9 mg kg-1, n = 5) prolonged the cycle length of the tachycardia by 114 +/- 57% from 158 +/- 11 to 332 +/- 66 ms (P less than 0.05). 5. Both drugs terminated the atrial arrhythmia, but re-entry could be reinduced only in flecainide-treated dogs. Flecainide reduced ventricular ectopies by 89 +/- 19%, whereas clofilium did not change ventricular abnormal automaticity or maximum pacing cycle length that is necessary to overdrive the ventricle fully. 6. These data indicate that the dual model provides coexisting arrhythmias of different mechanisms in the same heart and that Class I and Class III anti-arrhythmic drugs may be differentiated from each other by the distinct patterns of pharmacological activities produced in this test system.
Wu
K M
KM
Department of Pharmacology, A.H. Robins Research Laboratories, Richmond, VA 23261.
Hunter
T
T
Proakis
A
A
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy*; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D005424:Flecainide / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D000644:Quaternary Ammonium Compounds; C022799:clofilium; D005424:Flecainide