AVE0118's Impact on Atrial Refractoriness and Antiarrhythmic Action in Pigs

The study's aim was to evaluate the effects of AVE0118, a new K(+) channel blocker, on atrial refractoriness, left atrial vulnerability, and monophasic action potentials in anesthetized pigs. It was compared with dofetilide, a selective I(Kr) blocker, to determine its potential for treating atrial fibrillation.

The atrial effective refractory period (ERP) was measured using the S1-S2-stimulus technique at different basic cycle lengths (BCL). The drugs' impact on inducing atrial tachyarrhythmias was also assessed. Additionally, the study recorded monophasic action potentials (MAP) to understand the influence of potassium channel blockers on repolarization.

Results showed that the left atrium had significantly shorter ERPs compared to the right atrium at all BCLs tested. AVE0118, administered intravenously, lengthened the atrial ERP and suppressed left atrial vulnerability without affecting the corrected QT (QTc) interval. At a dosage of 1 mg/kg, it increased the left atrial ERP more than the right, indicating a stronger effect on the left atrium. Furthermore, AVE0118 did not impact left ventricular ERP, MAP duration, or QT interval at 600 ms BCL. The drug also significantly prolonged atrial MAP early in the repolarization process. In contrast, dofetilide had a delayed and less pronounced effect on atrial MAP and increased the QTc interval, affecting right atrial ERP more than the left but not significantly inhibiting left atrial vulnerability.

In conclusion, AVE0118 demonstrated the ability to extend atrial ERP and exhibited potent antiarrhythmic effects without affecting ventricular repolarization in pigs.