Atenolol, but not mexiletine, protects against stimulus-induced ventricular tachycardia in a chronic canine model.
1. In a placebo-controlled study of the antiarrhythmic and electrophysiological properties of atenolol and mexiletine, programmed electrical stimulation (PES) was performed in three groups of six conscious greyhounds, 7-30 days after coronary artery ligation. 2. In the placebo group, repeated PES challenge resulted in the consistent induction of ventricular tachycardias (VT) in 4/6 dogs and ventricular fibrillation in 2/6. Atenolol prevented arrhythmia induction in 4/6 dogs, one continued to demonstrate a VT and one died (P less than 0.05 compared with placebo). In the mexiletine group 5/6 dogs continued to demonstrate a VT and one died. 3. Electrocardiographic parameters were not affected by any treatment. There was no change in blood pressure in any group but when compared with placebo, heart rate fell (P less than 0.05) after atenolol (256 micrograms kg-1) and increased (P less than 0.05) after mexiletine (16 mg kg-1). Effective (ERP) and functional (FRP) refractory periods did not change after mexiletine, but ERP was prolonged (P less than 0.05) after atenolol. 4. The results indicate that atenolol but not mexiletine is effective in preventing re-entrant arrhythmias in this conscious canine model. Antiarrhythmic efficacy may be related to a fall in heart rate and/or a prolongation of refractoriness.
Uprichard
A C
AC
Department of Therapeutics and Pharmacology, Queen's University of Belfast, Northern Ireland.
Harron
D W
DW
D000818:Animals; D000889:Anti-Arrhythmia Agents; D001262:Atenolol / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation; D004195:Disease Models, Animal; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008026:Ligation; D008297:Male; D008801:Mexiletine / Q000494:pharmacology*; D013610:Tachycardia / Q000188:drug therapy*
D000889:Anti-Arrhythmia Agents; D008801:Mexiletine; D001262:Atenolol