Comparison of the cardiac electrophysiological effects of flecainide and hydroquinidine in anesthetized dog: concentration-response relationship.
The concentration-dependent effects of flecainide and hydroquinidine were studied in closed-chest anesthetized dogs. The electrophysiological effects of three doses (i.v. infusions followed by an appropriate perfusion to plateau the plasma levels) of flecainide (1, 2, and 3.9 mg/kg) and hydroquinidine (2, 4, 7.5 mg/kg) were tested. Sinus cycle length, QRS duration, His-Purkinje and AV nodal conduction times, Wenckebach period, atrial, nodal, and ventricular refractory periods, and corrected QT interval were measured before and 30 min after the beginning of each bolus infusion. Both hydroquinidine and flecainide increased the sinus cycle length, and slowed cardiac conduction to different degrees. Hydroquinidine and flecainide prolonged ventricular conduction; flecainide had a greater effect at the His-Purkinje level. Hydroquinidine exhibited only a weak and nonsignificant effect at the AV node, whereas flecainide dramatically prolonged conduction and refractoriness. The two drugs increased AERP equally. The QT interval and ventricular refractoriness were similarly prolonged to the same extent by both drugs (32 and 35% after the third doses of hydroquinidine and flecainide, respectively). The high plasma flecainide levels reached in our study (1.47 and 2.9 micrograms/ml after the second and third doses, respectively) may explain these effects, which are unexpected for a class Ic agent. These results suggest that flecainide could increase the QT interval, like a class Ia drug when its plasma level exceeds the therapeutic range.
Laboratoire de Pharmacologie, Faculté de Saint-Antoine, Paris, France.
F
F
Chézalviel
J
J
Weissenburger
O
O
Ertzbischoff
J M
JM
Poirier
X
X
Harlé
J M
JM
Davy
M
M
Biour
G
G
Cheymol
D000758:Anesthesia; D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005260:Female; D005424:Flecainide / Q000097:blood / Q000494:pharmacology*; D006321:Heart / Q000503:physiopathology*; D006329:Heart Conduction System / Q000187:drug effects; D008297:Male; D011802:Quinidine / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D012849:Sinoatrial Node / Q000187:drug effects
C014486:hydroquinidine; D011802:Quinidine; D005424:Flecainide