The antiarrhythmic profile of the new compound
diprafenone was evaluated using various dog models relevant to conditions in humans. In 8 animals, dose related effects on intracardiac conduction, atrial and ventricular refractoriness, fibrillation thresholds and on hemodynamics were determined. In this part of the study also the comparative actions of
propafenone were assessed (8 animals). IN another 28 dogs the antiarrhythmic and antifibrillatory actions of
diprafenone following short-term
coronary occlusion and subsequent release were established. In additional 16 animals the effects of
diprafenone on "delayed" reperfusion arrhythmias following release of coronary artery occlusion after 2 h and on stimulus-induced
ventricular tachycardia in acute
myocardial infarction were investigated. The results show:
Diprafenone slows conduction through all parts of the AV-conduction system. The AH-interval is significantly prolonged, QRS-duration and ventricular repolarization are slightly lengthened, and both the atrial and ventricular refractory periods and fibrillation thresholds are markedly increased. Heart rate is slowed, aortic pressure and cardiac output are not significantly changed. Following acute short-term coronary artery occlusion, the incidence of
ventricular fibrillation is reduced, and the drop in the
ventricular fibrillation threshold is diminished. By contrast, the frequency of
ventricular fibrillation after release of short-term occlusion is not influenced. "Delayed" reperfusion arrhythmias, however, are completely abolished, and initiation of
ventricular tachycardia in
myocardial infarction can be easily prevented. With a predominant
local anesthetic mechanism of action and a potential additional beta-
sympatholytic activity, the new compound displays close similarities to
propafenone.(ABSTRACT TRUNCATED AT 250 WORDS)