Effect of sotalol against reperfusion-induced arrhythmias in Sprague-Dawley and Wistar rats.
The effect of (+/-)-sotalol (a beta-blocker with class III antiarrhythmic activity) against reperfusion-induced arrhythmias was studied in artificially ventilated, open-chest, Sprague-Dawley and Wistar rats. Coronary artery occlusion was produced for 5 min and reperfusion allowed for 10 min. A somewhat different arrhythmic profile was observed between saline-treated rats of the 2 strains studied, with more Sprague-Dawley rats experiencing an irreversible ventricular fibrillation (VF) upon reperfusion, compared to Wistar rats, in whom a combination of reversible ventricular tachycardia (VT) and VF was more frequently observed. No difference in action potential characteristics and ventricular effective refractory period determined in vitro, nor in myocardial noradrenaline content, was found between the 2 strains of rats. (+/-)-Sotalol (5 and 10 mg/kg, IV) showed marked beta-blocking activity and reduced the mean duration of VT-VF in both strains studied. It also produced similar increases in action potential duration and refractory period in vitro in these 2 strains. In a different series of experiments, the antiarrhythmic action of the racemic form was compared to that of (+)-sotalol using Wistar rats. (+)-Sotalol had much less beta-blocking activity, and was found to be similarly effective against reperfusion-induced VT-VF. It is concluded that the antiarrhythmic effect of sotalol against reperfusion-induced arrhythmias may not be related to beta-adrenergic blockade but probably to class III type activity. Despite differences in the profile of reperfusion-induced arrhythmias between Sprague-Dawley and Wistar rats, both strains were sensitive to the antiarrhythmic action of (+/-)-sotalol.
Lamontagne
D
D
Centre de Recherche, Hôpital du Sacré-Coeur de Montreal, Canada.
Rochette
L
L
Vermeulen
M
M
Yamaguchi
N
N
Nadeau
R
R
De Champlain
J
J
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D004594:Electrophysiology; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013015:Sotalol / Q000494:pharmacology*; D013045:Species Specificity; D014693:Ventricular Fibrillation / Q000517:prevention & control
D013015:Sotalol; D009638:Norepinephrine