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Combination of Sotalol and Quinidine in a Canine Model of Torsades de Pointes
Author(s) -
CHÉZALVIELGUILBERT FRÉDÉRIQUE,
DEPLANNE VALÉRIE,
DAVY JEANMARC,
POIRIER JEANMARIE,
XIA YONGZHONG,
CHEYMOL GEORGES,
WEISSENBURGER JACQUES
Publication year - 1998
Publication title -
journal of cardiovascular electrophysiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.193
H-Index - 138
eISSN - 1540-8167
pISSN - 1045-3873
DOI - 10.1111/j.1540-8167.1998.tb01842.x
Subject(s) - sotalol , quinidine , torsades de pointes , medicine , qt interval , antiarrhythmic agent , anesthesia , mexiletine , dofetilide , cardiology , pharmacology , heart disease , atrial fibrillation
Sotalol Plus Quinidine and Torsades de Pointes. 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 heen 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 quiuidine (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 (sotatol‐alone and sotalol‐plus‐quinidine) experiments 48 bours apart usiug 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, aud 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.