The antiarrhythmic effects of class1 drugs on atrial fibrillation (AF) have been believed to be due to prolongation of atrial ERP and reduction of intra-atrial conduction velocity. But their possible effects on the pulmonary vein (PV) or PV-Left atrial (LA) junction have been ignored. The aim of this study was to investigate the effects of class 1c drug on the substrates of the AF originating from PV using experimental model.

Methods: In 27 open chest dogs, the procedures were carried out to induce AF by stimulating bilateral cervical vagal nerves after applying aconitine on a main branch of right (n=20) or left (n=7) PV. Class1c drug, pilsicainide (1mg/kg/5min.), was administered during the induced arrhythmia and its effects were evaluated. Before and after the drug administration, electrophysiologic study was performed using the electrodes placed in the atria and PVs and a mapping plaque with 128 electrodes placed on the atrial surface.

Results: Sustained AF, which started from the very rapid activation in an aconitine-applied PV (cycle length=CL: 61.2 ms), was induced in 21 of 27 dogs, and the tachycardia originating from the PV with regular coupling interval (=PV tachycardia) was induced in 6 dogs. Sustained AF was terminated by pilsicainide in 20 of 21 dogs (95%). Before the AF termination PV-LA dissociation phenomenon was observed in 5 of 20 dogs. Pilsicainide prolonged markedly the CL of PV tachycardia from 158 ms to 309 ms (p<0.001), and the PV-LA interval from 41.4 ms to 57.5 ms (p<0.005). Atrial ERP was prolonged from 90.0 ms to 107.5 ms (p<0.05), and conduction velocity was reduced from 73.2 cm/s to 55.2 cm/s (p<0.05). After pilsicainide, atrial burst pacing induced sustained AF in 3, while non-sustained AF in 12 of 20 dogs. Rapid PV activation was observed in all of sustained AF dogs, but only 1 of 12 non-sustained AF dogs. The mean plasma concentration of pilsicainide was 2.13 μg/ml (therapeutic range of pilsicainide: 0.3~0.9 μg/ml).

Conclusion: PV-originating AF was terminated by class1c-drug, which also suppressed the inducibility and sustainability of AF in the canine model. These antiarrhythmic effects appeared to be not only on the atria but the PV and PV-LA junction, which should be taken into account in evaluating the effects of the antiarrhythmic drugs on AF.