Antiarrhythmic effect of a sotalol-mexiletine combination on induced ventricular tachycardia in dogs.
Mexiletine was recently shown to antagonize the effects of sotalol on repolarization of canine Purkinje fibers. The significance of this interaction for the antiarrhythmic properties of these drugs remains unknown. The antiarrhythmic effects of sotalol and mexiletine alone and in combination on induced ventricular tachycardias (VTs) were assessed in 20 conscious dogs with chronic infarction. Electrophysiological measurements and programmed stimulation were performed before and after the infusion of sotalol (4 mg/kg) or mexiletine (4 mg/kg), and after infusion of the combination. The electrophysiological parameters didn't change after mexiletine. Sotalol alone and the combination both similarly prolonged the QT interval and VERP. Induction of VT by programmed stimulation was not prevented by mexiletine, but the cycle length of monomorphic VT was increased in 7 of 10 dogs. The induction of VT was prevented by sotalol (11/16 dogs), but VTs were not slowed significantly. Sotalol plus mexiletine prevented VT as did sotalol alone (11/16 dogs). The combination also increased the cycle length of VT in all eight dogs with monomorphic VT. Thus, the antagonism shown in vitro appears to have no consequences in this model. On the contrary, the sotalol-mexiletine combination showed some additive antiarrhythmic effects on induced VT in dogs.
Chézalviel
F
F
Laboratoire de Pharmacologie, Faculté de Médecine Saint Antoine, Paris, France.
Weissenburger
J
J
Guhennec
C
C
Jagueux
M
M
Davy
J M
JM
Vernhet
L
L
Simandoux
V
V
Poirier
J M
JM
Cheymol
G
G
D000818:Animals; D003331:Coronary Vessels / Q000502:physiology; D004285:Dogs; D004338:Drug Combinations; D004558:Electric Stimulation; D004562:Electrocardiography / Q000187:drug effects; D004594:Electrophysiology; D006439:Hemodynamics / Q000187:drug effects; D008801:Mexiletine / Q000494:pharmacology*; D009203:Myocardial Infarction / Q000188:drug therapy / Q000503:physiopathology; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D013015:Sotalol / Q000494:pharmacology*; D017180:Tachycardia, Ventricular / Q000188:drug therapy* / Q000503:physiopathology
D004338:Drug Combinations; D008801:Mexiletine; D013015:Sotalol