ABSTRACT
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.
Subject(s)
Coronary Disease/drug therapy , Flecainide/therapeutic use , Myocardial Reperfusion Injury/drug therapy , Ventricular Fibrillation/drug therapy , Animals , Blood Pressure/drug effects , Coronary Disease/physiopathology , Dogs , Electrocardiography , Flecainide/blood , Heart Rate/drug effects , Myocardial Reperfusion Injury/physiopathology , Ventricular Fibrillation/physiopathologyABSTRACT
Little information exists regarding the effect of heart rate on arrhythmias induced by coronary reperfusion. We therefore evaluated the effects of different heart rates on arrhythmias following canine coronary artery occlusion and reperfusion. Dogs were paced at either 350 msec cycle length (171 bpm; n = 30) or 480 msec cycle length (125 bpm; n = 30). They were then subjected to a 20-minute occlusion of the proximal left anterior descending coronary artery, followed by sudden reperfusion. Ligated vessel perfusion bed size (myocardial "at risk") was measured with monastral blue and red dyes. The incidence of both occlusion and reperfusion arrhythmias correlated with the myocardium at risk. Dogs paced at 171 bpm had more ventricular ectopic depolarizations (37/1000 beats vs 8/1000 beats, p less than 0.01) and a higher incidence of ventricular tachycardia during occlusion than those paced at 125 bpm (67% vs 33%, p less than 0.05). Dogs paced at the faster rate also had a higher incidence of ventricular tachycardia (83% vs 60%, p = 0.08) and ventricular fibrillation (70% vs 40%, p less than 0.05) after reperfusion. Thus, heart rate can have a substantial effect on occlusion and reperfusion arrhythmias and should be considered when making therapeutic interventions and risk assessments in this setting.
