L-type calcium current recovery versus ventricular repolarization: preserved membrane-stabilizing mechanism for different QT intervals across species
L-type calcium current recovery versus ventricular repolarization: preserved membrane-stabilizing mechanism for different QT intervals across species
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DOI：
10.1016/j.hrthm.2007.09.025
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发表时间：
2008-02-01
期刊：
影响因子：
5.5
通讯作者：
Yan, Gan-Xin
中科院分区：
文献类型：
--
作者：
Guo, Donglin;Zhou, Jun;Yan, Gan-Xin
长QT综合征与可能导致尖端扭转型室性心动过速（TdP）的早期后除极（EAD）相关。有趣的是，在生理条件下，校正的QT间期似乎与不同物种的体重成正比。目的本研究的目的是测试L-型钙电流的恢复是否（I-Ca，I-L）埃兹的主要电荷载流子，从其失活状态匹配心室复极时间，以及这种关系的损害是否导致EAD和TdP的发展。在从牛、狗、兔和豚鼠心脏分离的经动脉灌注的左心室楔形块中，同时记录心外膜、内膜或内膜下的心电图。结果心室复极时间（90%复极动作电位时程[APD 90]）在豚鼠194.7 ± 1.8 ms ~奶牛370.2 ± 9.9 ms之间，与左室壁厚度呈线性相关。C1、L恢复的时间常数（tau）与APD（90）成正比，使tau/APD（90）的比值在不同种属间处于相对较窄的范围内，尽管心室复极时间有显著差异。具有TdP风险的药物通过延长复极时间和/或加速I-Ca、I-L恢复而破坏这种内在平衡，导致能够启动TdP的埃兹的出现。结论I-Ca、（L）恢复与心室复极之间的适当平衡是复极期心室动作电位的“生理稳定器”。
BACKGROUND Long QT syndrome is associated with early afterdepolarization (EAD) that may result in torsade de pointes (TdP). Interestingly, the corrected QT interval seems to be proportional to body mass across species under physiologic conditions.OBJECTIVE The purpose of this study was to test whether recovery of L-type calcium current (I-Ca,I-L) the primary charge carrier for EADs, from its inactivated state matches ventricular repolarization time and whether impairment of this relationship leads to development of EAD and TdP.METHODS Transmembrane action potentials from the epicardium, endocardium, or subendocardium were recorded simultaneously with a transmural ECG in arterially perfused Left ventricular wedges isolated from cow, dog, rabbit, and guinea pig hearts. I-Ca,I-L recovery was examined using action potential stimulation in isolated Left ventricular myocytes.RESULTS The ventricular repotarization time (action potential duration at 90% repolarization [APD90]), ranging from 194.7 +/- 1.8 ms in guinea pig to 370.2 +/- 9.9 ms in cows, was linearly related to the thickness of the left ventricular wall among the species studied. The time constants (tau) Of C,,L recovery were proportional to APD(90), making the ratios of tau to APD(90) fall into a relatively narrow range among these species despite markedly different ventricular repolarization time. Drugs with risk for TdP in humans were shown to impair this intrinsic balance by either prolongation of the repolarization time and/or acceleration of I-Ca,I-L recovery, leading to the appearance of EADs capable of initiating TdP.CONCLUSION An adequate balance between I-Ca,(L) recovery and ventricular repolarization serves as a "physiologic stabilizer" of ventricular action potentials in repolarization phases.