Development of a rapid and economic in vivoelectrocardiogram platform for cardiovascular drug assay and electrophysiology research in adult zebrafish

Min-Hsuan Lin,Lawrence Yu-Min Liu,Wangta Liu,Yung-Jen Chuang,Chi-Chun Lee,Yu-Fu Chen,Huang-Cheng Chou

doi:10.1038/s41598-018-33577-7

Abstract

Zebrafish is a popular and favorable model organism for cardiovascular research, with an increasing number of studies implementing functional assays in the adult stage. For example, the application of electrocardiography (ECG) in adult zebrafish has emerged as an important tool for cardiac pathophysiology, toxicity, and chemical screen studies. However, few laboratories are able to perform such functional analyses due to the high cost and limited availability of a convenient in vivo ECG recording system. In this study, an inexpensive ECG recording platform and operation protocol that has been optimized for adult zebrafish ECG research was developed. The core hardware includes integration of a ready-to-use portable ECG kit with a set of custom-made needle electrode probes. A combined anesthetic formula of MS-222 and isoflurane was first tested to determine the optimal assay conditions to minimize the interference to zebrafish cardiac physiology under sedation. For demonstration, we treated wild-type zebrafish with different pharmacological agents known to affect cardiac rhythms in humans. Conserved electrophysiological responses to these drugs were induced in adult zebrafish and recorded in real time. This economic ECG platform has the potential to facilitate teaching and training in cardiac electrophysiology with adult zebrafish and to promote future translational applications in cardiovascular medicine.

Highlights

Electrophysiology is a unique component of biomedical science capable of investigating the electrical properties of an individual cell, organ, or complete organism in the context of physiology
We explored the use of the kit on adult zebrafish ECG for more advanced research applications by re-designing the specialized electrode probe for this new purpose
The zebrafish ECG system consisted of a three-needle electrode probe, two micromanipulators to hold the pectoral and abdominal needles, an ECG kit, and a laptop computer preloaded with the provided software

Summary

Introduction

Electrophysiology is a unique component of biomedical science capable of investigating the electrical properties of an individual cell, organ, or complete organism in the context of physiology. Multiple electrodes are attached to specific sites on test subject’s body surface to record the electrical signals generated from the cardiac conduction system, which represent the polarization and depolarization of cardiac muscle tissues. Since ECG reflects in vivo cardiac function, current FDA (Food and Drug Administration) regulation requires pharmaceutical companies to perform animal ECG assessments for cardiac toxicity when developing a new drug at the preclinical stage. These assessments are required to avoid adverse drug effects on the human heart, such as arrhythmia or heart failure. We anticipate that the devices and protocol described in this study can be established in any laboratory, which would greatly benefit educational and research practices with zebrafish

Methods

Results

Conclusion