Mechanisms of the preventive effect of pilsicainide on atrial fibrillation originating from the pulmonary vein.

背景：吡西卡尼被证明能终止肺静脉源性房颤，然而，它是否能预防诱导性房颤还不清楚。

方法和结果：在电刺激六个麻醉狗颈部迷走神经和分离的经乙酰胆碱灌注的心房时，快速起搏左上肺静脉和右房游离壁以诱发房颤。所有狗模型在应用吡西卡尼之前，不同起搏位置快速起搏都导致了房颤，吡西卡尼(1 mg/kg)能通过阻滞左上肺静脉和左房游离壁之间的电传导预防房颤发生，但是相同剂量的吡西卡尼并不能预防起搏左房游离壁所诱导的房颤。吡西卡尼能部分恢复经乙酰胆碱灌注导致的动作电位持续时间缩短。在所有的分离实验中，吡西卡尼能通过阻滞左上肺静脉和左房连接间的电传导而预防房颤的发生。

结论：实验结果表明：1、阻滞左上肺静脉和左房连接间电传导是吡西卡尼预防迷走诱导的左上肺静脉起源房颤的机制。2、吡西卡尼预防左上肺静脉起源房颤比右房起源房颤更为有效。

　　（来源：Circ J. 2007 Nov;71(11):1805-14.）

Mechanisms of the preventive effect of pilsicainide on atrial fibrillation originating from the pulmonary vein.

Hirose M, Ohkubo Y, Takano M, Hamazaki M, Sekido T, Yamada M.
Department of Molecular Pharmacology, Shinshu University School of Medicine.

Background It has been shown that pilsicainide terminates atrial fibrillation (AF) by pharmacologic pulmonary vein (PV) isolation. However, whether it can prevent AF induction originating from the PV by the same mechanism is still uncertain.

Methods and Results Rapid pacing from the left superior PV (LSPV) and the right atrial free wall (RAF) was performed to induce AF during electrical stimulation of both cervical vagal nerves in 6 anesthetized dogs and during the infusion of acetylcholine (ACh) in 8 isolated atria. Rapid pacing induced AF in all dogs, regardless of the pacing site, before pilsicainide. Pilsicainide (1 mg/kg) prevented AF during rapid pacing from the LSPV, with an impulse conduction block between the LSPV and the left atrial free wall (LAF). However, the same dose of pilsicainide did not prevent AF when pacing was performed from the RAF. Pilsicainide partially restored the action potential duration shortened by ACh infusion and prevented AF with an impulse conduction block at the LSPV-left atrial junction in all isolated preparations tested.

Conclusion The results suggest that (1) impulse conduction block at the LSPV-LA junction is the underlying mechanism of pilsicainide-induced prevention of vagally-induced AF originating from the LSPV and (2) pilsicainide is more effective at preventing AF originating from the LSPV than that from the RA. (Circ J 2007; 71: 1805 - 1814).
PMID: 17965507 [PubMed - in process]