钙震荡和 T 波不稳定先于获得性长 QT 综合征 2 型的室性心律失常。
Calcium oscillations and T-wave lability precede ventricular arrhythmias in acquired long QT type 2.
机构信息
Department of Medicine, Cardiovascular Institute, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
出版信息
Heart Rhythm. 2010 Nov;7(11):1686-94. doi: 10.1016/j.hrthm.2010.06.032. Epub 2010 Jul 3.
BACKGROUND
Alternans of intracellular Ca(2+) (Ca(i)) underlies T-wave alternans, a predictor of cardiac arrhythmias. A related phenomenon, T-wave lability (TWL), precedes torsades de pointes (TdP) in patients and animal models with impaired repolarization. However, the role of Ca(i) in TWL remains unexplored.
OBJECTIVE
This study investigated the role of Ca(i) dynamics on TWL in a noncryoablated rabbit model of long QT syndrome type 2 (LQT2) using simultaneous measurements of Ca(i) transient (CaT), action potentials (APs), and electrocardiogram (ECG) during paced rhythms and focused on events that precede ventricular ectopy.
METHODS
APs and CaTs were mapped optically from paced Langendorff female rabbit hearts (n = 8) at 1.2-s cycle length, after atrioventricular node ablation. Hearts were perfused with normal Tyrode solution, then with dofetilide (0.5 μM), and reduced [K(+)] (2 mM) and [Mg(2+)] (0.5 mM) to elicit LQT2. Lability of ECG, voltage, and Ca(i) signals were evaluated during regular paced rhythm, before and after dofetilide perfusion.
RESULTS
In LQT2, lability of Ca(i), voltage, and ECG signals increased during paced rhythm, before the appearance of early afterdepolarizations (EADs). LQT2 resulted in AP prolongation and multiple (1 to 3) additional Ca(i) upstrokes, whereas APs remained monophasic. When EADs appeared, Ca(i) rose before voltage upstrokes at the origins of propagating EADs. Interventions (i.e., ryanodine and thapsigargin, n = 3 or low Ca and nifedipine, n = 4) that suppressed Ca(i) oscillations also abolished EADs.
CONCLUSION
In LQT2, Ca(i) oscillations (Ca(i)O) precede EADs by minutes, indicating that they result from spontaneous sarcoplasmic reticulum Ca(2+) release rather than spontaneous I(Ca,L) reactivation. Ca(i)O likely produce oscillations of Na/Ca exchange current, I(NCX). Depolarizing I(NCX) during the AP plateau contributes to the generation of EADs by reactivating Ca(2+) channels that have recovered from inactivation. TWL reflects CaTs and APs lability that occur before EADs and TdP.
背景
细胞内钙（Ca(i)）的交替是 T 波交替的基础，T 波交替是心律失常的预测指标。在复极化受损的患者和动物模型中，与 T 波交替相关的现象 T 波不稳定性（TWL）先于尖端扭转型室性心动过速（TdP）出现。然而，Ca(i) 在 TWL 中的作用仍未得到探索。
目的
本研究使用钙瞬变（CaT）、动作电位（AP）和心电图（ECG）的同步测量，在非冷冻消融的兔 2 型长 QT 综合征（LQT2）模型中研究 Ca(i)动力学对 TWL 的作用，并在起搏节律期间对事件进行了重点研究，这些事件发生在室性心律失常之前。
方法
在房室结消融后，以 1.2 秒的心动周期从起搏 Langendorff 雌性兔心（n = 8）进行光学 AP 和 CaT 映射。心脏用正常 Tyrode 溶液灌注，然后用多非利特（0.5 μM）、降低[K(+)]（2 mM）和[Mg(2+)]（0.5 mM）以引发 LQT2。在起搏节律之前和之后，评估常规起搏节律期间 ECG、电压和 Ca(i)信号的不稳定性，在多非利特灌注之前和之后。
结果
在 LQT2 中，在早期后除极（EADs）出现之前，Ca(i)、电压和 ECG 信号的不稳定性在起搏节律期间增加。LQT2 导致 AP 延长和多个（1 到 3 个）额外的 Ca(i)上冲，而 AP 仍然是单相的。当 EADs 出现时，在传播 EAD 的起源处，Ca(i)在电压上冲之前上升。抑制 Ca(i)振荡的干预措施（即 Ryanodine 和 Thapsigargin，n = 3 或低 Ca 和 Nifedipine，n = 4）也消除了 EADs。
结论
在 LQT2 中，Ca(i)振荡（Ca(i)O）在 EADs 之前提前出现几分钟，表明它们是由自发肌浆网 Ca(2+)释放引起的，而不是由自发 I(Ca,L)再激活引起的。Ca(i)O 可能产生 Na/Ca 交换电流 I(NCX)的振荡。在 AP 平台期间去极化的 I(NCX)通过使已经从失活中恢复的 Ca(2+)通道重新激活，有助于产生 EADs。TWL 反映了在 EAD 和 TdP 之前出现的 CaTs 和 APs 不稳定性。
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