Short-Long Heart Rate Variation Increases Dispersion of Action Potential Duration in Long QT Type 2 Transgenic Rabbit Model.
Short-Long Heart Rate Variation Increases Dispersion of Action Potential Duration in Long QT Type 2 Transgenic Rabbit Model.
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短-长心率变化增加了长 QT 2 型转基因兔模型中动作电位持续时间的离散度。
DOI：
10.1038/s41598-019-51230-9
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发表时间：
2019
影响因子：
4.6
通讯作者：
Choi,Bum-Rak
中科院分区：
文献类型：
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作者：
Kim,TaeYun;Jeng,Paul;Hwang,JungMin;Pfeiffer,Zachary;Patel,Divyang;Cooper,LeroyL;Kossidas,Konstantinos;Centracchio,Jason;Peng,Xuwen;Koren,Gideon;Qu,Zhilin;Choi,Bum-Rak
长QT综合征2型（LQT2）的多形性室性心动过速的开始与短-长RR间期的特征性心电图模式有关。我们假设这种特征性模式增加了LQT2中的APD弥散，从而促进心律失常。在LQT2、LQT1和LMC转基因兔模型中，采用随机刺激方法研究了APD弥散及其对前两个周期长度（CLs）的依赖性。结果表明，短-长RR模式与LQT2兔APD弥散度较大相关，而与LQT1兔无相关。APD与前两个CLs （APDn= C + α1CLn−1+ α2CLn−2）的关系的多变量分析表明，α1（APD恢复斜率）在LQT2中最大且不均匀，而在LQT1中均匀，增强了LQT2中长CLn−1下APD的分散。α2（短期记忆）在LQT2中呈阴性，在LQT1中呈阳性，α1在LQT2中的空间分布与α2呈负相关，这解释了为什么短-长组合在LQT2中导致APD弥散较大，而在LQT1中没有。综上所述，短-长RR模式仅在LQT2兔中通过异质APD恢复和短期记忆增加APD离散度，强调LQT综合征心律失常的基因型特异性触发。
The initiation of polymorphic ventricular tachycardia in long QT syndrome type 2 (LQT2) has been associated with a characteristic ECG pattern of short-long RR intervals. We hypothesize that this characteristic pattern increases APD dispersion in LQT2, thereby promoting arrhythmia. We investigated APD dispersion and its dependence on two previous cycle lengths (CLs) in transgenic rabbit models of LQT2, LQT1, and their littermate controls (LMC) using random stimulation protocols. The results show that the short-long RR pattern was associated with a larger APD dispersion in LQT2 but not in LQT1 rabbits. The multivariate analyses of APD as a function of two previous CLs (APDn= C + α1CLn−1+ α2CLn−2) showed that α1(APD restitution slope) is largest and heterogeneous in LQT2 but uniform in LQT1, enhancing APD dispersion under long CLn−1in LQT2. The α2(short-term memory) was negative in LQT2 while positive in LQT1, and the spatial pattern of α1was inversely correlated to α2in LQT2, which explains why a short-long combination causes a larger APD dispersion in LQT2 but not in LQT1 rabbits. In conclusion, short-long RR pattern increased APD dispersion only in LQT2 rabbits through heterogeneous APD restitution and the short-term memory, underscoring the genotype-specific triggering of arrhythmias in LQT syndrome.