Abstract
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.
Highlights
In the practice of in vivo surface electrocardiogram (ECG) recording for adult zebrafish, only a single lead, either bipolar or unipolar, is used due to the physical limitation of the zebrafish chest size
Electrical heart axis of a given ECG component in a given plane cannot be determined from a single lead (Liu et al, 2016; Zhao et al, 2020)
The direction of electrical axis in the frontal plane is expressed in terms of an angle that it makes with the horizontal, which is lead-I axis or 0◦ in the Cabrera system (Figure 1C; Dieuaide, 1921; Proger and Davis, 1930; Ferrer, 1972; Surawicz and Knilans, 2008)
Summary
In the practice of in vivo surface electrocardiogram (ECG) recording for adult zebrafish, only a single lead, either bipolar or unipolar, is used due to the physical limitation of the zebrafish chest size. In bipolar single-lead ECG recording for adult zebrafish, the conventional approach is to position the positive electrode cranial to the heart and the negative electrode caudal to the heart (Milan et al, 2006; Sun et al, 2009; Liu et al, 2016; Lin et al, 2018; Zhao et al, 2019, 2020). The rationale for this conventional practice is to align polarities of zebrafish and human ECG components (P, QRS, and T) to ease comparison. This practice may lead to the erroneous inference that the cardiac electrical vectors of the two species are similar, which in turn leads to misinterpretation of the clinical relevance of the adult zebrafish heart as a model for human cardiac electrophysiology and arrhythmia studies
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