Cardioprotective effects of various class I antiarrhythmic drugs in canine hearts

Abstract This study was designed to clarify the cardioprotective effects of various class I antiarrhythmic drugs, i.e., aprindine, disopyramide, flecainide, lidocaine, mexiletine, pentisomide and propafenone, on the ischemic heart. Sixty-one adult mongrel dogs were classified into eight groups according to premedication: 1) control group, physiologic saline solution was administered intravenously 25 min before left anterior descending coronary artery ligation; 2) aprindine group, 3 mg/kg body weight of aprindine intravenously; 3) disopyramide group, 2 mg/kg of disopyramide intravenously; 4) flecainide group, 2 mg/kg of flecainide intravenously followed by drip infusion of 100 μg/kg per min; 5) lidocaine group, 2 mg/kg of lidocaine intravenously followed by drip infusion of 100 gmg/kg per min; 6) mexiletine group, 3 mg/kg per min of mexiletine intravenously followed by drip infusion of 15 μ/kg per min; 7) pentisomide group, 5 mg/kg intravenously; and 8) propafenone group, 2 mg/kg intravenously. Arterial blood pressure and electrocardiogram were monitored throughout the experiment. Two hours after coronary occlusion, the heart was excised. Myocardial mitochondria were prepared and mitochondrial function (the respiratory control index and the rate of oxygen consumption in state 111) was measured polarographically. Fractionation of myocardial tissues was performed and the lysosomal enzyme (N-acetyl-β-glucos-aminidase and β-glucuronidase) activities among fractions were measured. No significant hemodynamic changes were observed compared with the control group except for those in the disopyramide and flecainide groups; that is, decrease in heart rate without changes in blood pressure compared with the control group was observed. All antiarrhythmic drugs effectively prevented the development of ventricular arrhythmias associated with ischemia. Two hours of coronary occlusion induced mitochondrial dysfunction and leakage of lysosomal enzymes. In contrast, each antiarrhythmic drug without exception lessened mitochondrial dysfunction and prevented the leakage of lysosomal enzymes concomitantly. These results indicate that class I antiarrhythmic drugs have cardioprotective effects on ischemic myocardium.