Effects of flecainide on occlusion and reperfusion arrhythmias in dogs.
To assess flecainide's ability to suppress ventricular fibrillation during reperfusion, we compared flecainide acetate (2 mg/kg i.v.) with saline placebo in 50 pentobarbital-anesthetized dogs undergoing proximal anterior descending coronary artery occlusion for 20 min followed by sudden release. Treatment selection was blinded and randomized. Flecainide (1 mg/kg) was given for 5 min before ligation and 1 mg/kg over the 20 min occlusion period. Heart rate, blood pressure, myocardium at risk, and QRS duration before drug infusion were similar between treatment groups. Flecainide prolonged the QRS duration 12% with no effect on heart rate or blood pressure. Dogs successfully cardioverted from ventricular fibrillation during occlusion were subjected to reperfusion. One of the 25 dogs treated with placebo fibrillated during occlusion, whereas 13 of the 25 dogs treated with flecainide fibrillated during occlusion and 10 of these 13 could not be resuscitated. Thirteen of the 25 dogs in the placebo group fibrillated during reperfusion, whereas 3 of the remaining 15 dogs in the flecainide treatment group fibrillated during reperfusion. The proarrhythmic effects of flecainide during occlusion confound interpretation of its antiarrhythmic activity during reperfusion. Thus, although flecainide may have prevented ventricular fibrillation during reperfusion, it clearly caused ventricular fibrillation during occlusion in this preparation of acute myocardial ischemia.
Lederman
S N
SN
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.
Wenger
T L
TL
Bolster
D E
DE
Strauss
H C
HC
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003327:Coronary Disease / Q000188:drug therapy* / Q000503:physiopathology; D004285:Dogs; D004562:Electrocardiography; D005424:Flecainide / Q000097:blood / Q000627:therapeutic use*; D006339:Heart Rate / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology; D014693:Ventricular Fibrillation / Q000188:drug therapy* / Q000503:physiopathology
D005424:Flecainide