Delayed afterdepolarization in intact canine sinoatrial node as a novel mechanism for atrial arrhythmia.

Delayed afterdepolarization in intact canine sinoatrial node as a novel mechanism for atrial arrhythmia.
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DOI:
10.1111/j.1540-8167.2010.01905.x
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发表时间:
2011-04
影响因子:
2.7
通讯作者:
Chen PS
Chen PS
中科院分区:
医学3区
文献类型:
--
作者:
Joung B;Zhang H;Shinohara T;Maruyama M;Han S;Kim D;Choi EK;On YK;Lin SF;Chen PS

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最近的证据表明,自发的肌浆网 Ca 释放和 Na-Ca 交换器电流激活有助于窦房结 (SAN) 的自动化。这些发现表明 SAN 活动可能共享自动性和触发性活动背后的机制。本研究的目的是检验以下假设:自发的、非电压门控的细胞内 Ca (Cai) 升高可能会在异丙肾上腺素输注期间诱导完整 SAN 中的延迟后除极 (DAD)。我们同时绘制了 31 个孤立的 Langendorff 灌注犬右心房 (RA) 的 Cai 和膜电位。异丙肾上腺素增加了上级 SAN 的心率和舒张晚期 Cai 升高 (LDCAE),从而导致所有 31 个 RA 中 SAN 自动化程度一致。然而,在异丙肾上腺素输注期间,4 例 RA 中短暂观察到 DAD 样舒张期去极化 (DD)。这些类似 DAD 的 DD 发生在 LDCAE 之前,但没有触发完整的动作电位。与窦性搏动相比,DAD 样 DD 之前的 LDCAE 振幅更小(0.41 ± 0.08 AU 对比 0.48 ± 0.07 AU,p=0.001),斜率也更小(3.7 ± 1.3 AU/s 对比 4.8 ± 1.4 AU/s,p=0.001)。类似 DAD 的 DD 的耦合间隔比之前的正常心跳要长(407 ± 48 ms vs. 371 ± 44 ms,p=0.002)。在大多数情况下,卓越 SAN 的异丙肾上腺素诱导的 LDCAE 诱导了完整的动作电位。然而,如果 LDCAE 太小而无法触发动作电位,那么它只能诱导 DAD 样 DD。 DAD 样 DD 未能持续触发窦性搏动是房性心律失常发生的一种新机制。
Recent evidence indicates that spontaneous sarcoplasmic reticulum Ca release and Na-Ca exchanger current activation contribute to the sinoatrial node (SAN) automaticity. These findings suggest that SAN activity may share mechanisms that underlie both automaticity and triggered activity. The aim of this study is to test the hypothesis that spontaneous, non-voltage gated, intracellular Ca (Cai) elevation may induce delayed afterdepolarization (DAD) in intact SAN during isoproterenol infusion. We simultaneously mapped Cai and membrane potential in 31 isolated Langendorff-perfused canine right atriums (RA). Isoproterenol increased heart rate and late diastolic Cai elevation (LDCAE) of the superior SAN, leading to consistent SAN automaticity in all 31 RAs. However, DAD-like diastolic depolarizations (DD) were transiently observed in 4 RAs during isoproterenol infusion. These DAD-like DDs were preceded by LDCAE, but did not trigger a full action potential. The LDCAE preceding DAD-like DDs had smaller amplitude (0.41 ± 0.08 AU vs. 0.48 ± 0.07 AU, p=0.001) and less steep slopes (3.7 ± 1.3 AU/s vs. 4.8 ± 1.4 AU/s, p=0.001) than that of sinus beats. The coupling interval of DAD-like DDs was longer than that of the preceding normal beats (407 ± 48 ms vs. 371 ± 44 ms, p=0.002). The isoproterenol-induced LDCAE of superior SAN induced a full action potential in most cases. However, if the LDCAE was too small to trigger an action potential, then it induces only DAD-like DD. The failure of DAD-like DD to consistently trigger a sinus beat is a novel mechanism of atrial arrhythmogenesis.
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