Myles Rachel C, Burton Francis L, Cobbe Stuart M, Smith Godfrey L
BHF Glasgow Cardiovascular Research Centre, University of Glasgow, University Place, Glasgow, G12 8TA, UK.
J Mol Cell Cardiol. 2008 Jul;45(1):1-10. doi: 10.1016/j.yjmcc.2008.03.024. Epub 2008 Apr 9.
T-wave alternans is considered a potentially useful clinical marker for the risk of ventricular arrhythmia in patients with heart disease. Cellular repolarisation alternans is thought to underlie T-wave alternans, and moreover, to cause re-entrant ventricular arrhythmia. This review examines the experimental and clinical evidence linking repolarisation alternans and T-wave alternans with the occurrence of ventricular arrhythmia. Repolarisation alternans, manifest as alternating changes in action potential duration, is observed in isolated ventricular cardiomyocytes and in multicellular preparations. Its underlying causes are discussed particularly with respect to the role of intracellular Ca(2+). The repolarisation alternans observed at the single cell level is compared to the alternating behaviour observed in isolated multicellular preparations including the perfused ventricular wedge and Langendorff perfused heart. The evidence concerning spatial differences in repolarisation alternans is considered, particularly the situation where adjacent regions of myocardium exhibit repolarisation alternans of different phases. This extreme behaviour, known as discordant alternans, is thought to produce marked gradients of repolarisation that can precipitate unidirectional block and re-entrant ventricular arrhythmias. Finally, the difficulties in extrapolating between experimental models of alternans and arrhythmias and the clinical manifestation are discussed. The areas where experimental evidence is weak are highlighted, and areas for future research are outlined.
T波交替被认为是心脏病患者室性心律失常风险的一种潜在有用的临床标志物。细胞复极交替被认为是T波交替的基础，而且会导致折返性室性心律失常。本综述探讨了将复极交替和T波交替与室性心律失常发生相关联的实验和临床证据。复极交替表现为动作电位持续时间的交替变化，在分离的心室心肌细胞和多细胞制剂中均可观察到。尤其就细胞内Ca(2+)的作用讨论了其潜在原因。将单细胞水平观察到的复极交替与在包括灌注心室楔形组织和Langendorff灌注心脏在内的分离多细胞制剂中观察到的交替行为进行了比较。考虑了有关复极交替空间差异的证据，特别是心肌相邻区域表现出不同相位复极交替的情况。这种极端行为，称为不一致交替，被认为会产生明显的复极梯度，从而引发单向阻滞和折返性室性心律失常。最后，讨论了在交替和心律失常的实验模型与临床表现之间进行推断的困难。突出了实验证据薄弱的领域，并概述了未来的研究领域。
