Mechanisms of ventricular rate adaptation as a predictor of arrhythmic risk
Mechanisms of ventricular rate adaptation as a predictor of arrhythmic risk
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DOI：
10.1152/ajpheart.00936.2009
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发表时间：
2010-05-01
影响因子：
4.8
通讯作者：
Rodriguez, Blanca
中科院分区：
文献类型：
--
作者：
Pueyo, Esther;Husti, Zoltan;Rodriguez, Blanca
Pueyo E，Husti Z，Hornyik T，Baczko I，拉古纳P，Varro A，Rodriguez B.心室率适应机制作为心肌梗死风险的预测因子。Am J Physiol Heart Circ Physiol 298：H1577-H1587，2010.首次发表于2010年3月5日; doi：10.1152/ajpheart.00936.2009。QT间期（QTI）对心率（HR）突然变化的适应性已被确定为临床风险标志物。本研究探讨了QTI频率适应的离子机制及其与糖尿病风险的关系。计算机模拟和实验记录在人类和犬心室组织中被用来研究离子基础的QTI和动作电位时程（APD）的突然变化，在HR与临床研究中常用的协议。在模拟中，90%QTI适应的时间为3.5分钟，与人类的实验和临床数据一致。APD适应遵循类似的动力学，在中层心肌细胞（2.5分钟）比在内膜和心外膜细胞（3.5分钟）更快。QTI和APD在HR突然变化后的两个阶段适应：快速初始阶段，时间常数< 30 s，主要与L型钙和缓慢延迟整流钾电流有关;第二个缓慢阶段，由细胞内钠浓度（[Na+]（i））动力学驱动，>2 min。由于Na+/K+泵电流抑制导致的[Na+]（i）动力学改变导致延长的频率适应，并与促心律失常风险增加相关，如动作电位三角测量和失活后更快的L型钙电流恢复所示，导致早期后除极的形成。总之，本研究表明，延长的QTI适应可能是Na+/K+泵抑制后[Na+]（i）动力学改变的指标，因为它发生在缺血或心力衰竭患者中。心率适应延长患者心律失常风险增加可能是由于早期后除极形成风险增加。
Pueyo E, Husti Z, Hornyik T, Baczko I, Laguna P, Varro A, Rodriguez B. Mechanisms of ventricular rate adaptation as a predictor of arrhythmic risk. Am J Physiol Heart Circ Physiol 298: H1577-H1587, 2010. First published March 5, 2010; doi: 10.1152/ajpheart.00936.2009.-Protracted QT interval (QTI) adaptation to abrupt heart rate (HR) changes has been identified as a clinical arrhythmic risk marker. This study investigates the ionic mechanisms of QTI rate adaptation and its relationship to arrhythmic risk. Computer simulations and experimental recordings in human and canine ventricular tissue were used to investigate the ionic basis of QTI and action potential duration (APD) to abrupt changes in HR with a protocol commonly used in clinical studies. The time for 90% QTI adaptation is 3.5 min in simulations, in agreement with experimental and clinical data in humans. APD adaptation follows similar dynamics, being faster in midmyocardial cells (2.5 min) than in endocardial and epicardial cells (3.5 min). Both QTI and APD adapt in two phases following an abrupt HR change: a fast initial phase with time constant < 30 s, mainly related to L-type calcium and slow-delayed rectifier potassium current, and a second slow phase of >2 min driven by intracellular sodium concentration ([Na+](i)) dynamics. Alterations in [Na+](i) dynamics due to Na+/K+ pump current inhibition result in protracted rate adaptation and are associated with increased proarrhythmic risk, as indicated by action potential triangulation and faster L-type calcium current recovery from inactivation, leading to the formation of early afterdepolarizations. In conclusion, this study suggests that protracted QTI adaptation could be an indicator of altered [Na+](i) dynamics following Na+/K+ pump inhibition as it occurs in patients with ischemia or heart failure. An increased risk of cardiac arrhythmias in patients with protracted rate adaptation may be due to an increased risk of early afterdepolarization formation.