We have developed a dual electrophysiologic test that allows measurement of both antireentry and antifibrillatory activities of potential antiarrhythmics in the same anesthetized dog. The reentry portion of the model was created surgically by a Y-shaped crushing around the tissue between the superior and inferior vena cava and tissue parallel to the AV groove. The pacing-induced
tachycardia that results from circus movements around the tricuspid ring is very persistent in duration and regular in cycle length. The antifibrillatory activities were assessed by determination of the
ventricular fibrillation threshold (VFT) using train-stimuli method. Control VFT was measured every 15-20 min in duplicate and followed by induction of atrial reentry. A
drug was infused to intervene the atrial
tachycardia. After the conversion of the
arrhythmia (either by
drug regimens or pacing), postdrug VFT was measured, again in duplicate.
Bethanidine (20 mg/kg),
procainamide (30 mg/kg), and
WY-48986 (10 mg/kg), a Class III antiarrhythmic, were evaluated in this dual test.
Bethanidine and
procainamide prolonged the cycle length of atrial reentry to a greater extent than
WY-48986. The atrial arrhythmias were consistently terminated by
procainamide and
WY-48986 whereas
bethanidine converted the
tachycardias in one of the five dogs studied. All three agents elevated VFT with
bethanidine producing higher values than
procainamide and
WY-48986. In conclusion, the dual electrophysiologic testing system offers both economic and scientific advantages for the study of modes of action of antiarrhythmic agents.