Development and optimization of an in vivo electrocardiogram recording method and analysis program for adult zebrafish

Abstract

Clinically pertinent electrocardiogram (ECG) data from model systems, such as zebrafish, are crucial for illuminating factors contributing to human cardiac electrophysiology abnormalities and disease. Current zebrafish ECG collection strategies have not adequately addressed the consistent acquisition of high-quality traces or sources of phenotypic variation that could obscure data interpretation. Thus, we developed a novel platform to ensure high-quality recording of in vivo subdermal adult zebrafish ECGs and zERG (Zebrafish ECG Reading GUI), a program to acquire measurements from traces commercial software cannot examine due to erroneous peak calling. We evaluate normal ECG trait variation, revealing the intervals are highly reproducible while wave amplitude variation appears largely driven by recording artifacts, and identify sex and body size as potential confounders to PR, QRS, and QT intervals. With this framework, we characterize the effect of the class I anti-arrhythmic drug flecainide acetate on adults, provide support for the impact of a Long QT syndrome model, and establish power calculations for this and other studies. These results highlight our pipeline as a robust approach to evaluate zebrafish models of human cardiac electrophysiologic phenotypes.

The Effect of Hypothermia and Osmotic Shock on the Electrocardiogram of Adult Zebrafish

“…This discrepancy between the QT-RR relationship maybe due to a number of factors such as the strain of fish [45], the experimental conditions, anesthesia, and other types of treatment. Recently, other confounding factors such as sex and body weight have also been described [46]. This suggests that the best protocol when studying zebrafish ECG is to first characterize the QT-RR of a given strain of fish in standardized experimental conditions before going further.…”

Characterization of the adult zebrafish electrocardiogram

“…This discrepancy between the QT-RR relationship maybe due to a number of factors such as the strain of fish [42], the experimental conditions, anesthesia and other types of treatment. Recently, other confounding factors such as sex and body weight have also been described [43]. This suggests that the best protocol when studying zebrafish ECG is to first characterize the QT-RR of a given strain of fish in standardized experimental conditions before going further.…”

Golden Standard or Obsolete Method? Review of ECG Applications in Clinical and Experimental Context

“…In the last two decades, zebrafish became a valuable model in experimental cardiology due to its fast reproduction, low maintenance cost, easy breeding, possibility of genetic manipulation, extensive developmental characterization, and optical transparency ( Gut et al, 2017 ; Duong et al, 2021 ). Moreover, zebrafish cardiac electric activity is comparable to that of man ( Duong et al, 2021 ). Therefore, several devices for ECG recording in zebrafish were introduced.…”

“…Most of the approaches require anesthesia or paralysis of the fish. Recently, devices for long-term monitoring of zebrafish were developed and validated ( Duong et al, 2021 ; Le et al, 2022 ).…”