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Combination of sotalol and quinidine in a canine model of torsades de pointes: no increase in the QT-related proarrhythmic action of sotalol.

AbstractINTRODUCTION:
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.
AuthorsF Chézalviel-Guilbert, V Deplanne, J M Davy, J M Poirier, Y Z Xia, G Cheymol, J Weissenburger
JournalJournal of cardiovascular electrophysiology (J Cardiovasc Electrophysiol) Vol. 9 Issue 5 Pg. 498-507 (May 1998) ISSN: 1045-3873 [Print] UNITED STATES
PMID9607458 (Publication Type: Comparative Study, Journal Article)
Chemical References
  • Anti-Arrhythmia Agents
  • Sodium Chloride
  • Sotalol
  • Quinidine
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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