Use of diprafenone, a new potent propafenone-analogue, in acute experimental myocardial ischaemia and infarction.
Diprafenone (D) is a new class I c antiarrhythmic agent, structurally similar to propafenone. We assessed its antiarrhythmic and anti-fibrillatory effects during acute coronary occlusion and reperfusion and the underlying mechanisms of action by epicardial mapping of the conduction delay; also the effects of D on stimulus-induced ventricular tachycardia 18-24 h after permanent coronary occlusion were assessed. Experiments were performed on 32 mongrel dogs with temporary coronary occlusion lasting 20 min and subsequent reperfusion. Control ligations in 16 animals were compared to ligations after pretreatment with D (2 mg kg-1) in 6 dogs. In another 10 dogs a permanent coronary occlusion was performed and the inducibility of ventricular tachycardia was assessed by programmed stimulation before and after D (2.4 mg kg-1). Following D the incidence of ventricular arrhythmias including rapid ventricular tachycardias was not reduced during acute coronary occlusion, but even enhanced in some animals, whereas the frequency of ventricular fibrillation was diminished. No significant difference was observed following reperfusion. Conduction delay in the ischaemic area increased significantly during both phase Ia and Ib following pretreatment with D. During reperfusion conduction delay was significantly prolonged in the D group. At 18-24 h after permanent coronary occlusion the new compound proved to be highly effective in suppressing stimulus-induced ventricular tachycardia. During acute coronary occlusion D diminished the incidence of ventricular fibrillation. D is similar to other class Ic compounds; however, there are some important differences with respect to its additional beta-sympatholytic activity.
Thale
J
J
University Hospital, Department of Cardiology and Angiology, Münster, FRG.
Gülker
H
H
Hindricks
G
G
Haverkamp
W
W
Bender
F
F
D000208:Acute Disease; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000517:prevention & control; D002304:Cardiac Pacing, Artificial; D055598:Chemical Phenomena; D002621:Chemistry; D003327:Coronary Disease / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D004285:Dogs; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects; D006352:Heart Ventricles; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy*; D011405:Propafenone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D014693:Ventricular Fibrillation / Q000209:etiology / Q000517:prevention & control
C047546:diprafenone; D011405:Propafenone