Fig 1.
Comparison of 3D model geometry to 3 dpf zebrafish anatomy.
A) lateral, B) ventral, C) front brightfield views; D) lateral, E) ventral F) front view of model. Different coloured regions highlight the distinct heart regions within the model.
Fig 2.
Image of 3 dpf zebrafish heart compared to model heart geometry.
All images are from a ventral view. A) depiction of a 3 dpf Tg(fli-1:EGFP) zebrafish with a fluorescing heart, B) solid view of heart geometry, C) model heart geometry cut through showing the distinct regions.
Fig 3.
Comparison between recorded action potentials [9] from a 2 dpf heart and model action potentials.
A) atrium B) atrioventricular band C) ventricle. Action potentials were recorded from explanted 2 dpf hearts at room temperature using patch pipettes and current clamp techniques.
Table 1.
Final parameter values used within the model.
Table 2.
Initial conditions.
Table 3.
Comparison between model and recorded action potential properties.
Table 4.
Activation wave conduction velocities in an adult human and a 3 dpf zebrafish heart.
Table 5.
Conductivity values used within the model for each heart region.
Fig 4.
Temporal sequence of transmembrane potential (Vm).
The propagation of an action potential through the heart is shown at different times. Nine time steps were chosen to show the progression of the action potentials through all stages of the cardiac cycle. A) the heart at rest B) atrial depolarisation C) ventricular depolarisation D) the end of atrial repolarisation and ventricular plateau stage E,F,G,H) ventricular repolarisation I) returning to the rest state. The wave originates at the sinoatrial region then it progresses across the atrium, through the atrioventricular band and into the ventricle. An animation is given in S2 File.
Fig 5.
Electrode positions used for electrocardiogram recording with the corresponding measurements and model positions in a 3 dpf zebrafish.
A) Processed image in ventral view showing electrodes in different recording positions. Electrode 1 is positioned over the atrium, electrode 2 over the atrioventricular band and electrode 3 over the ventricle, B) A representative atrial recording showing the key ECG features: P wave, QRS complex, T wave, PR interval and QT interval, C) A representative middle recording, D) A representative ventricular recording, E) Expanded ventral view of equivalent electrode positions within the model, F) Close-up ventral view of electrode positions over the heart. The signals from positions 1 and 3 were measured at the same time on the same zebrafish, that from position 2 was measured on a different animal and hence no voltage scale is shown. A positive deflection in the ECG is caused by the depolarisation wave moving towards the recording electrode
Fig 6.
Model ECG at different positions with overlaid action potentials.
A) atrial position, B) middle position, C) ventricular position. Red dots mark the key stages in each ECG (P, R and T waves). Atrial repolarisation is also marked (AR, green circle). No voltage scale is shown as the action potentials were scaled so that the ECG was visible on the same axes.
Fig 7.
Comparison between ECG recordings and model ECG.
The recorded ECG at three positions was compared to the model output. A) model comparison to atrial recording, B) model comparison to middle recording and C) model comparison to ventricular recording. Model 1 has fitted action potential durations, model 2 has a reduced action potential duration that gives a similar QT length to the recordings. No voltage scale is shown as the model ECG voltages are much smaller than the recordings.
Table 6.
A comparison between model ECG (model 2 from Fig 8) parameters and measured ECG parameters.
Table 7.
A comparison between model relative peak heights and measured relative peak heights.
Fig 8.
Maximum R wave voltage and R wave percentage change.
The point at which the R wave is at its maximum at 0.84 s from the start of the simulation. A) zoomed out ventral view of the model with the point of maximum voltage intensity labelled, B) close-up ventral view with the maximum point labelled, C) close-up ventral view showing ten different points distributed around the ventricle as seen on the surface of the body, D) percentage of the maximum R wave voltage at each point.