Zhao Yali, Chen Connie, Yun Morgan, Issa Thomas, Lin Andrew, Nguyen Thao P
The Cardiovascular Research Laboratory, Division of Cardiology, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA, United States.
Front Physiol. 2021 Jul 23;12:708938. doi: 10.3389/fphys.2021.708938. eCollection 2021.
Zebrafish is a popular high-throughput vertebrate model to study human cardiac electrophysiology, arrhythmias, and myopathies. One reason for this popularity is the purported striking similarities between zebrafish and human electrocardiograms (ECGs). However, zebrafish electrical heart axes were unknown. It is impossible to define heart axis based on single-lead ECG because determination of an electrical heart axis in the frontal plane requires the use of the hexaxial reference system (or Cabrera system) derived from Einthoven's triangle. Construction of Einthoven's triangle requires simultaneous ECG recording from at least two Einthoven bipolar leads. Therefore, we systematically constructed the first zebrafish Einthoven's triangle by simultaneous bipolar dual-lead ECG recording to determine for the first time the three frontal electrical heart axes using the Cabrera system. Comparing zebrafish with human Einthoven's triangle reveals that their normal frontal electrical axes were reflections of each other across 0° in the Cabrera system. The responsible mechanisms involve zebrafish vs. human cardiac activation propagating in the same direction along the heart horizontal axis but in opposite directions along the heart longitudinal axis. The same observations are true for zebrafish vs. human cardiac repolarization. This study marks a technical breakthrough in the first bipolar dual-lead ECG recording in live adult zebrafish to construct for the first time zebrafish Einthoven's triangle. This first systematic analysis of the actual differences and similarities between normal adult zebrafish and human Einthoven's triangles unmasked differences and similarities in the underlying cardiac axis mechanisms. Insights of the live adult zebrafish main heart axis and its three frontal electrical heart axes provide critical contextual framework to interpret the clinical relevance of the adult zebrafish heart as model for human cardiac electrophysiology.
斑马鱼是一种用于研究人类心脏电生理学、心律失常和心肌病的常用高通量脊椎动物模型。其受欢迎的一个原因是据称斑马鱼和人类心电图（ECG）之间存在显著相似性。然而，斑马鱼的心脏电轴此前并不为人所知。基于单导联心电图无法确定心脏轴，因为在额面确定心脏电轴需要使用源自爱因托芬三角的六轴参考系统（或卡布雷拉系统）。构建爱因托芬三角需要至少从两个爱因托芬双极导联同时记录心电图。因此，我们通过同步双极双导联心电图记录系统地构建了首个斑马鱼爱因托芬三角，首次使用卡布雷拉系统确定了三个额面心脏电轴。将斑马鱼与人类爱因托芬三角进行比较发现，在卡布雷拉系统中，它们正常的额面电轴在0°处相互镜像。其相关机制涉及斑马鱼与人类心脏激活沿心脏横轴方向相同，但沿心脏纵轴方向相反。斑马鱼与人类心脏复极的情况也是如此。这项研究标志着在成年活体斑马鱼中首次进行双极双导联心电图记录以构建首个斑马鱼爱因托芬三角方面取得了技术突破。这项对正常成年斑马鱼与人类爱因托芬三角之间实际差异和相似性的首次系统分析揭示了潜在心脏轴机制中的差异和相似性。对成年活体斑马鱼主心脏轴及其三个额面心脏电轴的深入了解为解释成年斑马鱼心脏作为人类心脏电生理学模型的临床相关性提供了关键的背景框架。
