Key result
The exposed heart configuration provided the most reliable and reproducible ECG recordings in adult zebrafish, allowing for accurate determination of the QT-RR relationship using the Holzgrefe correction.
Why the study?
Whether the zebrafish model can determine drug cardiac toxicity via ECG analysis remains an open question, and recording configurations severely affect waveforms and derived parameters.
The exposed heart configuration is the most reliable method for recording ECGs and assessing the QT-RR relationship in adult zebrafish, providing a robust model for preclinical cardiotoxicity screening.
Supports zebrafish ECG for preclinical cardiotoxicity screening; leaves open clinical translation.
Background The use of zebrafish to explore cardiac physiology has been widely adopted within the scientific community. Whether this animal model can be used to determine drug cardiac toxicity via electrocardiogram (ECG) analysis, is still an ongoing question. Several reports indicate that the recording configuration severely affects the ECG waveforms and its derived-parameters, emphasizing the need for improved characterization. Methods ECGs were recorded from adult zebrafish hearts in 3 different configurations (unexposed heart, exposed heart and extracted heart) to identify the most reliable method to explore ECG recordings at baseline and in response to commonly used clinical therapies. Results We found that the exposed heart configuration provided the most reliable and reproducible ECG recordings of waveforms and intervals. We were unable to determine T-wave morphology in unexposed hearts. In extracted hearts, ECG intervals were lengthened and P-waves were unstable. However, in the exposed heart configuration, we were able to reliably record ECGs and subsequently establish the QT-RR relationship (Holzgrefe correction) in response to changes in heart rate. Conclusions The exposed heart configuration appears to be the most reliable technique to record ECGs in adult zebrafish. In this configuration, the QT-RR relationship, an important parameter in cardiac toxicity evaluation, can be determined using the Holzgrefe correction.
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Arel et al. (2022) studied Healthy (n=20). Exposed heart ECG configuration vs. Unexposed heart and extracted heart configurations was evaluated on Reliability of ECG waveforms and intervals (QT-RR relationship). The exposed heart configuration provided the most reliable and reproducible ECG recordings in adult zebrafish, allowing for accurate determination of the QT-RR relationship using the Holzgrefe correction.
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