Antiarrhythmic effects of losartan and enalapril in canine pulmonary vein sleeve preparations.
Antiarrhythmic effects of losartan and enalapril in canine pulmonary vein sleeve preparations.
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DOI：
10.1111/j.1540-8167.2010.01972.x
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发表时间：
2011-06
影响因子：
2.7
通讯作者：
Antzelevitch C
中科院分区：
文献类型：
--
作者：
Sicouri S;Cordeiro JM;Talarico M;Antzelevitch C
血管紧张素转换酶（ACE）抑制剂和血管紧张素II受体阻滞剂（ARB）是治疗房颤（AF）的“上游”治疗的原型。肺静脉袖引起的异位活动在房颤的发展中起着重要作用。使用标准微电极技术记录犬灌流左上级或下级肺静脉袖的跨膜动作电位。使用乙酰胆碱（ACh，1 µM）、异丙肾上腺素（1 µM）、高钙（[Ca 2 +]o= 5.4 mM）或其组合诱导早期或延迟后除极（埃兹或DAD）和触发活动。ARB氯沙坦（1 µM，n=5）和ACE抑制剂依那普利（10 µM，n=5）在动作电位时程、动作电位上升的最大速率（Vmax）、基础周期长度为200至2000 ms时的动作电位振幅或起飞电位。氯沙坦（1 µM）和依那普利（10-20 µM）显著减弱或抑制了6/6（氯沙坦）和4/5（依那普利）PV袖制备物在快速起搏后暴露于ACh、异丙肾上腺素或高钙引起的埃兹和DAD诱导的触发活动。在这些浓度下，氯沙坦或依那普利均未改变酶分离的心房肌细胞中的Ca 2+或K+通道电流。我们的数据表明，除了减少心房结构重构的“上游”作用外，ACE抑制剂和ARB通过抑制导致AF和其他房性心律失常的触发因素发挥“直接”抗心律失常作用。
Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II-receptor blockers (ARBs) are prototypes of “upstream” therapy for the management of atrial fibrillation (AF). Ectopic activity arising from the PV sleeves plays a prominent role in the development of AF. Transmembrane action potentials were recorded from canine superfused left superior or inferior PV sleeves using standard microelectrode techniques. Acetylcholine (ACh, 1 µM), isoproterenol (1 µM), high calcium ([Ca2+]o=5.4mM) or a combination was used to induce early or delayed afterdepolarizations (EADs or DADs) and triggered activity. The ARB losartan (1 µM, n=5) and the ACE inhibitor enalapril (10 µM, n=5) produced no significant change in action potential duration, maximum rate of rise of action potential upstroke (Vmax), action potential amplitude or take-off potential at basic cycle lengths of 200 to 2000 ms. Losartan (1 µM) and enalapril (10–20 µM) markedly attenuated or suppressed EADs and DAD–induced triggered activity elicited by exposure of the PV sleeves to ACh, isoproterenol or high calcium following rapid pacing in 6 of 6 (losartan) and 4 of 5 (enalapril) PV sleeve preparations. Neither losartan or enalapril altered Ca2+ or K+ channel currents in enzymatically-dissociated atrial myocytes at these concentrations. Our data suggest that in addition to their “upstream” effects to reduce atrial structural remodeling, ACE inhibitors and ARBs exert a “direct” antiarrhythmic effect by suppressing triggers responsible for the genesis of AF and other atrial arrhythmias.
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影响因子：
2.7
作者：
Sicouri S;Belardinelli L;Carlsson L;Antzelevitch C
通讯作者：
Antzelevitch C
影响因子：
4.8
作者：
Salehian, Omid;Healey, Jeff;Lonn, Eva
通讯作者：
Lonn, Eva
影响因子：
5.5
作者：
Wongcharoen, Wanwarang;Chen, Yao-Chang;Chen, Shih-Ann
通讯作者：
Chen, Shih-Ann
影响因子：
5.5
作者：
Patterson, E;Po, SS;Lazzara, R
通讯作者：
Lazzara, R
影响因子：
24
作者：
Patterson, E;Lazzara, R;Po, SS
通讯作者：
Po, SS