Assessment of the antiarrhythmic profile of the new class I agent diprafenone.
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)
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003327:Coronary Disease / Q000188:drug therapy; D004285:Dogs; D004562:Electrocardiography; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D011405:Propafenone / Q000031:analogs & derivatives*; D011427:Propiophenones / Q000494:pharmacology* / Q000627:therapeutic use
D000889:Anti-Arrhythmia Agents; D011427:Propiophenones; C047546:diprafenone; D011405:Propafenone