Antiarrhythmic and antifibrillatory actions of the beta adrenergic receptor antagonist, dl-sotalol.

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 to 7 days after a 2-hr 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 five 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 treatment with sotalol. However, the increase in ventricular refractoriness (156 +/- 5 msec predrug vs. 191 +/- 7 msec post 8 mg/kg of sotalol, P less than .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 hr (13 of 20, 65% vs. control, 1 of 15, 7%; P less than .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.(ABSTRACT TRUNCATED AT 250 WORDS)

• Authors: E Patterson, J J Lynch, B R Lucchesi
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 230 Issue 2 Pg. 519-26 (Aug 1984) ISSN: 0022-3565 [Print] United States
• PMID: 6086892 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Receptors, Adrenergic, beta
• Sotalol

Topics

• Animals
• Arrhythmias, Cardiac (prevention & control)
• Disease Models, Animal
• Dogs
• Electric Stimulation
• Electrocardiography
• Male
• Myocardial Infarction (complications)
• Receptors, Adrenergic, beta (metabolism)
• Sotalol (therapeutic use)
• Ventricular Fibrillation (prevention & control)