Potent antiarrhythmic effects of chronic amiodarone in canine pulmonary vein sleeve preparations.

Potent antiarrhythmic effects of chronic amiodarone in canine pulmonary vein sleeve preparations.
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DOI:
10.1111/j.1540-8167.2009.01449.x
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发表时间:
2009-07
影响因子:
2.7
通讯作者:
Antzelevitch C
Antzelevitch C
中科院分区:
医学3区
文献类型:
--
作者:
Sicouri S;Belardinelli L;Carlsson L;Antzelevitch C

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研究慢性胺碘酮对犬肺静脉(PV)袖状标本和左心室楔形标本电生理的影响。胺碘酮通常用于治疗室性和室上性心律失常。肺静脉引起的异位活动在房颤(AF)的发生中起着重要作用。使用标准微电极技术评价从未处理和长期胺碘酮处理犬(胺碘酮,40 mg/kg,每日一次,持续6周)中分离的灌注PV袖套(左上级或下部)和动脉灌注左心室(LV)楔形制备物的电生理学特征。在肺静脉袖中,慢性胺碘酮(n = 6)诱导90%复极化时的动作电位时程(APD 90)显著增加,Vmax显著使用依赖性降低,导致长周期时的1:1激动失败(对照组的基本周期长度为124 ± 15 ms,慢性胺碘酮组为420 ± 320 ms [P < 0.01])。舒张期兴奋阈值由0.3 ± 0.2 mA提高到1.8 ± 0.7 mA(P < 0.01)。使用乙酰胆碱(ACh,1 μM)、高钙([Ca 2 +]o = 5.4 mM)、异丙肾上腺素(Iso,1 μM)或其组合,在6/6个未处理的PV袖中可诱导延迟和晚期3相早期后除极和触发活动,但在5个慢性胺碘酮处理的PV袖中仅1个。与从胺碘酮处理动物中分离的LV楔形块制备物相比,PV袖套中的Vmax、传导速度和1:1激动失败受到的影响更大。结果表明,慢性胺碘酮优先抑制犬肺静脉袖产生的致炎底物和触发物的强效作用。
To examine the effects of chronic amiodarone on the electrophysiology of canine pulmonary vein (PV) sleeve preparations and left ventricular wedge preparation. Amiodarone is commonly used for the treatment of ventricular and supraventricular arrhythmias. Ectopic activity arising from the PV plays a prominent role in the development of atrial fibrillation (AF). Standard microelectrode techniques were used to evaluate the electrophysiological characteristics of superfused PV sleeve (left superior or inferior) and arterially perfused left ventricular (LV) wedge preparations isolated from untreated and chronic amiodarone-treated dogs (amiodarone, 40 mg/kg daily for 6 weeks). In PV sleeves, chronic amiodarone (n = 6) induced a significant increase in action potential duration at 90% repolarization (APD90) and a significant use-dependent reduction in Vmax leading to 1:1 activation failure at long cycle lengths (basic cycle length of 124 ± 15 ms in control vs 420 ± 320 ms after chronic amiodarone [P < 0.01]). Diastolic threshold of excitation increased from 0.3 ± 0.2 to 1.8 ± 0.7 mA (P < 0.01). Delayed and late phase 3 early afterdepolarizations and triggered activity could be induced in PV sleeve preparations using acetylcholine (ACh, 1 μM), high calcium ([Ca2+]o = 5.4 mM), isoproterenol (Iso, 1 μM), or their combination in 6 of 6 untreated PV sleeves, but in only 1 of 5 chronic amiodarone-treated PV sleeve preparations. Vmax, conduction velocity, and 1:1 activation failure were much more affected in PV sleeves versus LV wedge preparations isolated from amiodarone-treated animals. The results point to potent effects of chronic amiodarone to preferentially suppress arrhythmogenic substrates and triggers arising from the PV sleeves of the dog.
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