Abstract | INTRODUCTION: Clinical treatment with a combination of Class IA and III antiarrhythmic drugs is not recommended, as they both favor bradycardia-dependent proarrhythmic events such as torsades de pointes (TdP). However, this theoretical additive effect on ventricular repolarization has never been demonstrated and could be questioned as other Class I drugs, such as mexiletine, a Class IB drug, limit the number of sotalol-induced TdP in dogs with AV block, suggesting the possibility of an antagonistic action of Class I properties against Class III effects. METHODS AND RESULTS: We compared the electrophysiologic and proarrhythmic effects of sotalol (Class III) alone and combined with quinidine (Class IA) in a canine model of acquired long QT syndrome. Seven hypokalemic (K+: 3 +/- 0.1 mEq/L) dogs with chronic AV block had a demand pacemaker implanted and set at a rate of 25 beats/min. They were submitted to two ( sotalol-alone and sotalol-plus- quinidine) experiments 48 hours apart using a randomized cross-over protocol. They were pretreated with quinidine (10 mg/kg + 1.8 mg/kg per hour) or saline infused throughout the experiment, and given sotalol (4.5 mg/kg + 1.5 mg/kg per hour) for 2 hours, 30 minutes after the beginning of the pretreatment infusion during both experiments. Ventricular and atrial cycle lengths were similarly increased by sotalol after quinidine or saline. The sotalol-induced prolongation of the QT interval was significantly shorter in quinidine-pretreated dogs (24 +/- 7 msec after quinidine vs 40 +/- 8 msec after saline). Fewer dogs developed TdP: significantly during the first hour of infusion (1/7 sotalol-plus- quinidine vs 6/7 sotalol-alone dogs, P < 0.05) but nonsignificantly during the second hour (3/7 vs 6/7). CONCLUSION: In this model, the sotalol-plus- quinidine combination is at least no more arrhythmogenic than either of the drugs given alone.
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Authors | F Chézalviel-Guilbert, V Deplanne, J M Davy, J M Poirier, Y Z Xia, G Cheymol, J Weissenburger |
Journal | Journal of cardiovascular electrophysiology
(J Cardiovasc Electrophysiol)
Vol. 9
Issue 5
Pg. 498-507
(May 1998)
ISSN: 1045-3873 [Print] United States |
PMID | 9607458
(Publication Type: Comparative Study, Journal Article)
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Chemical References |
- Anti-Arrhythmia Agents
- Sodium Chloride
- Sotalol
- Quinidine
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Topics |
- Animals
- Anti-Arrhythmia Agents
(adverse effects, pharmacology)
- Arrhythmias, Cardiac
(chemically induced, physiopathology)
- Disease Models, Animal
- Dogs
- Drug Therapy, Combination
- Electrophysiology
- Infusions, Intravenous
- Quinidine
(adverse effects, pharmacology)
- Sodium Chloride
(pharmacology)
- Sotalol
(adverse effects, pharmacology)
- Torsades de Pointes
(drug therapy, physiopathology)
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