Universitätsklinikum des Saarlandes, Klinik für Innere Medizin III, Homburg/Saar, Germany.
Heart Rhythm. 2011 Dec;8(12):1933-9. doi: 10.1016/j.hrthm.2011.07.018. Epub 2011 Jul 20.
Negative tracheal pressure (NTP) during tracheal obstruction in obstructive apnea increases vagal tone and causes pronounced shortening of the atrial effective refractory period (AERP), thereby perpetuating atrial fibrillation (AF). The role of different atrial potassium channels under those conditions has not been investigated.
The purpose of this study was to evaluate the atrial effects of blockade of the late activated potassium current (I(Kr)) by sotalol, of blockade of the early activated potassium currents (I(Kur)/I(to)) by AVE0118, and of the multichannel blocker amiodarone during tracheal occlusions with applied NTP.
Twenty-one pigs were anesthetized, and an endotracheal tube was placed to apply NTP (up to -100 mbar) comparable to clinically observed obstructive sleep apnea for 2 minutes. Right AERP and AF inducibility were measured transvenously by a monophasic action potential recording and stimulation catheter.
Tracheal occlusion with applied NTP caused pronounced AERP shortening. AF was inducible during all NTP maneuvers. Blockade of I(Kr) by sotalol, blockade of I(Kur)/I(to) by AVE0118, and amiodarone did not affect NTP-induced AERP shortening, although they prolonged the AERP during normal breathing. Atropine given after amiodarone completely inhibited NTP-induced AERP shortening. The combined blockade of I(Kr) and I(Kur)/I(to) by sotalol plus AVE0118, however, attenuated NTP-induced AERP shortening and AF inducibility independent of the order of administration.
The atrial proarrhythmic effect of NTP simulating obstructive apneas is difficult to inhibit by class III antiarrhythmic drugs. Neither amiodarone nor blockade of I(Kr) or I(Kur)/I(to) attenuated NTP-induced AERP shortening. However, the combined blockade of I(Kur)/I(to) and I(Kr) suppressed NTP-induced AERP shortening.
在阻塞性呼吸暂停时，气管阻塞时的负气管压力（NTP）增加迷走神经张力，并导致心房有效不应期（AERP）明显缩短，从而使心房颤动（AF）持续存在。在这些条件下，不同心房钾通道的作用尚未得到研究。
本研究旨在评估索他洛尔阻断晚期激活钾电流（I（Kr））、AVE0118 阻断早期激活钾电流（I（Kur）/I（to））以及多通道阻滞剂胺碘酮在应用 NTP 时气管阻塞对心房的影响。
21 头猪被麻醉，并放置气管内导管以施加 NTP（高达-100 mbar），与临床观察到的阻塞性睡眠呼吸暂停相当持续 2 分钟。通过单相动作电位记录和刺激导管经静脉测量右心房 AERP 和 AF 可诱导性。
应用 NTP 进行气管阻塞导致 AERP 明显缩短。在所有 NTP 操作期间都可诱导 AF。索他洛尔阻断 I（Kr）、AVE0118 阻断 I（Kur）/I（to）以及胺碘酮均不影响 NTP 诱导的 AERP 缩短，尽管它们在正常呼吸期间延长了 AERP。胺碘酮后给予阿托品完全抑制 NTP 诱导的 AERP 缩短。然而，索他洛尔加 AVE0118 联合阻断 I（Kr）和 I（Kur）/I（to），独立于给药顺序，减轻 NTP 诱导的 AERP 缩短和 AF 可诱导性。
模拟阻塞性呼吸暂停的 NTP 的心房致心律失常作用难以通过 III 类抗心律失常药物抑制。胺碘酮或阻断 I（Kr）或 I（Kur）/I（to）均不能减轻 NTP 诱导的 AERP 缩短。然而，联合阻断 I（Kur）/I（to）和 I（Kr）可抑制 NTP 诱导的 AERP 缩短。
