Abstract 3497: Sodium Channel Blocker, Pilsicainide, Prevents Atrial Fibrillation Originating from the Pulmonary Veins by Pulmonary Vein Isolation in Isolated Arterially-Perfused Canine Atria
Introduction: Recent clinical studies have shown that the pulmonary vein (PV) isolation by radiofrequency catheter ablation is effective to prevent atrial fibrillation (AF) originating from the PVs. However, whether anti-arrhythmic drugs can prevent AF by pharmacological PV isolation is still unknown.
Methods and Results: First, to examine the effect of cholinergic intervention on impulse propagation at the left superior PV-left atrial (LSPV-LA) junction and on AF induction, high resolution optical mapping was used to measure action potentials from the posterior left atrium including the LSPV in the absence and during acetylcholine (ACh, 3 μM) infusion. Second, we also examined the effect of a sodium channel blocker, pilsicainide (3 and10 μM), on AF induction during ACh infusion. Recordings were made during 15 sec of constant pacing (cycle length (CL) = 400 -100 ms) from the LSPV in 8 isolated arterially perfused canine atria. Pilsicainide homogenously prolonged atrial action potential duration in the left atrium including the LSPV during ACh. In addition, repolarization gradient at the LSPV-LA junction is less than 3 ms/mm in all 8 preparations regardless of intervention. In the absence of ACh, LSPV pacing at a shorter CL (150–100 ms) caused conduction slowing at the LSPV-LA junction but induced AF in only one preparation. In contrast, during ACh, the shorter CL of LSPV pacing did not cause apparent conduction slowing but induced AT in all preparations tested. Pilsicainide (3 μM) caused conduction slowing at the junction regardless of pacing CL and did not prevent AF induction during ACh. However, pilsicainide (10 μM) caused unidirectional or bi-directional conduction block at the junction and prevented AF in all preparations tested. Interestingly, impulse propagation failure beyond the junction was associated with the decreased amplitude of optical signals in the LSPV.
Conclusion: These results suggest that decreases in PV atrial muscle excitability caused by pilsicainide potentiates source-sink mismatch at the LSPV-LA junction, which causes impulse propagation failure. Pilsicainide can prevent AT induction by pharmacological PV isolation.