A Comparitive Analysis of Zebrafish, Human, and Other Fish Cardiac Dynamics

Sudden cardiac death is often caused by ventricular fibrillations (VF), which are critical abnormalities in heart rhythm resulting from disruptions in the cardiac voltage and calcium electrophysiology. An important precursor to are alternans, which are period doubling bifurcations producing a long-short alternan duration pattern. Alternans are characterized as Period 2 arrythmia dynamics, which can increase into larger periods as the heart goes into more complex arrythmia regimes. This makes alternans a good predictor of VF, and the environmental environment for which they are formed can reveal information on how VF occurs and how it can be avoided. Zebrafish have been increasingly used to model electrophysiology and study alternan dynamics due to their similar action potential morphology, especially regarding drug development. But their specific alternan mechanism has not been studied and would have important implications for their use as models. It is also useful to compare this to other fish heart dynamics to understand how arrhythmia differences arise and how this can compare to different human arrythmia patterns.

This was done through optical mapping experiments. The hearts were stained using two different dyes that would fluoresce when illuminated by LEDs. Their emission spectrum shifts when there is a change in voltage and the heart, which produces a voltage over time graph. The heart is electrically stimulated over a range of periods to induce alternans, where the APD is plotted against the period to create a bifurcation plot – this will display the environment the alternans are produced in. This experiment was repeated for zebrafish, goldfish, and cichlids. It can be seen that zebrafish have a different alternan mechanism than humans due to their different alternan curves: zebrafish alternan following a square root curve while human hearts follow a linear curve. Similarly, cichlids also have a linear curve, while also displaying Period 3 dynamics, an indicator of fibrillatory dynamics. This has important implications for the use of zebrafish as cardiac models for human, and opens the door for new potential fish models.