Masonic Medical Research Laboratory, Utica, New York 13501-1787, USA.
J Cardiovasc Electrophysiol. 2011 Jun;22(6):698-705. doi: 10.1111/j.1540-8167.2010.01972.x. Epub 2010 Dec 16.
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 (Ca(2+) = 5.4 mM) 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 (V(max)), 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 nor enalapril altered Ca(2+) 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.
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）是管理心房颤动（AF）的“上游”治疗的原型。源自 PV 袖套的异位活动在 AF 的发展中起重要作用。
使用标准微电极技术从犬左上位或下位 PV 袖套记录跨膜动作电位。乙酰胆碱（ACh，1 μM）、异丙肾上腺素（1 μM）、高钙（Ca(2+) = 5.4 mM）或其组合用于诱导早期或延迟后除极（EAD 或 DAD）和触发活动。
ARB 洛沙坦（1 μM，n = 5）和 ACE 抑制剂依那普利（10 μM，n = 5）在基本心动周期长度为 200 至 2000 ms 时，对动作电位时程、动作电位上升最大速率（V(max)）、动作电位幅度或起始电位没有显著影响。洛沙坦（1 μM）和依那普利（10-20 μM）显著减弱或抑制了 6 个（洛沙坦）和 4 个（依那普利）PV 袖套制剂中，在快速起搏后暴露于 ACh、异丙肾上腺素或高钙时，EAD 和 DAD 诱导的触发活动。在这些浓度下，洛沙坦或依那普利均未改变酶解分离的心房心肌细胞中的 Ca(2+)或 K(+)通道电流。
我们的数据表明，除了减少心房结构重塑的“上游”作用外，ACE 抑制剂和 ARB 通过抑制负责 AF 和其他心房性心律失常发生的触发因素，发挥“直接”抗心律失常作用。
