Effects of pilsicainide on the atrial fibrillation threshold in guinea pig atria. A comparative study with disopyramide, lidocaine and flecainide.
The effects of pilsicainide, a new class Ic antiarrhythmic agent, on the atrial fibrillation threshold (AFT), the atrial effective refractory period (ERP), and the interatrial conduction time (ACT) in Langendorff-perfused guinea pig hearts were investigated. These effects were compared with those of disopyramide, lidocaine and flecainide. Whole guinea pig heart was perfused with Tyrode's solution containing acetylcholine (3 x 10(-7) M). Three indices were measured before and after the administration of the test drugs using right atrial extrastimulus and high frequency stimulation. Pilsicainide, disopyramide and flecainide (> or = 10(-6) M) all significantly increased the AFT. Both pilsicainide and flecainide (> or = 3 x 10(-6) M) significantly prolonged the ERP, but this prolongation was less pronounced than that observed with disopyramide. The ACT was significantly prolonged with pilsicainide (> or = 10(-6) M), and this prolongation was greater than that observed with disopyramide but less than that with flecainide. Lidocaine had no effects on any of the indices measured. In conclusion, pilsicainide had a preventive effect on the atrial fibrillation induced by a combination of acetylcholine and high frequency stimulation in guinea pig hearts, by increasing the atrial ERP and slowing the interatrial conduction. These effects may explain, in part, the clinical effectiveness of this drug on paroxysmal atrial fibrillation.
Inoue
M
M
Second Department of Medicine, Kyoto Prefectural University of Medicine, Japan.
Inoue
D
D
Ishibashi
K
K
Sakai
R
R
Omori
I
I
Yamahara
Y
Y
Asayama
J
J
Nakagawa
M
M
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001281:Atrial Fibrillation / Q000503:physiopathology*; D004206:Disopyramide / Q000494:pharmacology; D004594:Electrophysiology; D005260:Female; D005424:Flecainide / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006325:Heart Atria / Q000187:drug effects / Q000503:physiopathology; D066298:In Vitro Techniques; D008012:Lidocaine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male
D000889:Anti-Arrhythmia Agents; D008012:Lidocaine; C042288:pilsicainide; D004206:Disopyramide; D005424:Flecainide