ANTIARRHYTHMIC AND ANTIFIBRILLATORY ACTIONS OF THE BETA-ADRENERGIC-RECEPTOR ANTAGONIST, DL-SOTALOL

  • 1 January 1984
    • journal article
    • research article
    • Vol. 230  (2) , 519-526
Abstract
The antiarrhythmic and antifibrillatory actions of the .beta. adrenergic receptor antagonist, dl-sotalol, were examined in the canine heart subjected to myocardial ischemic injury. Programmed electrical stimulation of the heart was done 4-7 days after a 2-h occlusion followed by reperfusion of the left anterior descending coronary artery. The resulting dysrhythmias consisted of nonsustained ventricular tachycardia (n = 1), sustained ventricular tachycardia (n = 5) or polymorphous ventricular tachycardia degenerating to ventricular fibrillation (n = 3). After dl-sotalol (8 mg/kg), programmed stimulation failed to produce ventricular arrhythmias in 5 animals with only nonsustained ventricular tachycardia observed in the other animals. Epicardial activation delays produced in ischemically injured myocardium by premature ventricular stimuli were not altered by sotalol treatment. However, the increase in ventricular refractoriness (156 .+-. 5 ms predrug vs. 191 .+-. 7 ms post 8 mg/kg of sotalol, P < 0.01) prevented the introduction of premature ventricular stimuli at coupling intervals previously producing ventricular tachyarrhythmias despite the presence of continuous diastolic electrical activity recorded with epicardial composite electrodes over the region of chronic myocardial injury. In a conscious canine model which spontaneously develops ventricular fibrillation, dl-sotalol (2 mg/kg, n = 7; 8 mg/kg, n = 13) decreased the incidence of ventricular fibrillation and increased survival at 24 h (13 of 20, 65% vs. control, 1 of 15, 7%; P < 0.001). Composite electrograms recorded from the anterior and posteriorlateral surfaces of the heart demonstrated the rapid development of activation delays on the posteriorlateral surface with the appearance of ischemic ST segment changes. dl-Sotalol did not alter the duration of epicardial conduction delays. In sotalol-treated animals, bridging diastolic electrical activity frequently exceeded the T wave of the lead II electrocardiogram without the occurrence of ventricular tachycardia, or ventricular fibrillation. An antiarrhythmic and antifibrillatory action of dl-sotalol is demonstrated in the canine heart subjected to myocardial ischemic injury. Sotalol produces its salutary effects by its ability to prolong the ventricular effective refractory period in normal myocardium without altering ventricular conduction velocity.