Selective Class III Antiarrhythmic Properties of a Novel Agent, UK-66,914, During Chronic Myocardial Infarction

Antiarrhythmic Properties of UK- 66,914. UK-66,914 is a potent Class III antiarrhythmic agent that has no effect on conduction velocity in normal tissue in vitro. The present study was performed to evaluate the influence of UK-66,914 on conduction velocity in vivo in canine hearts with a previous myocardial infarction. Detailed three-dimensional mapping of the heart in vivo was obtained using simultaneous recordings from 232 transmural sites. In dogs with a chronic anterior myocardial infarction, UK-66,914 (50 μg/kg) did not alter conduction velocity in regions exhibiting normal conduction (gt; 50 cm/sec) or regions with slowed conduction ( 30 cm/sec, 15-30 cm/sec, or < 15 cm/sec, whereas procainamide significantly decreased conduction velocity at all three levels. Evaluation of the hemodynamic profile of UK-66,914 revealed no negative ionotropic effects in conscious dogs even at doses twentyfold those required to elicit increases in the effective refractory period. Therefore, UK-66,914 is a potent and specific Class III antiarrhythmic agent, which does not alter conduction velocity in hearts with a previous myocardial infarction and exerts no negative inotropic effects.