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

Lin, Ming–Fa; Chou, Huang-Cheng; Chen, Yu-Fu; Liu, Wangta; Lee, Chi-Chun; Liu, Lawrence Yu‐Min; Chuang, Yung-Jen

doi:10.1038/s41598-018-33577-7

Cited by 31 publications

(44 citation statements)

References 29 publications

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“…The zebrafish heart has only one atrium and one ventricle in contrast to the human heart with two atria and two ventricles (top row; right and left, respectively). However, despite its apparent anatomical simplicity, the zebrafish heart shares several ECG features with the human heart (bottom row; right and left, respectively) Therefore, the zebrafish heart has emerged as a surrogate model for human cardiac electrophysiology 5,12,13 . Figure 1 illustrates a small but distinct Q wave from a live, healthy 14-month-old zebrafish.…”

Section: Representative Resultsmentioning

confidence: 99%

“…First, in choosing the appropriate anesthetics and determining the minimal needed anesthesia concentration, depth, and duration, balance the anesthetic cardiotoxicities against the critical need to suppress motion artifacts and the a priori determination for a survival vs. terminal experimental design. Capitalizing on the synergistic potency of a combination of multiple anesthetics from different drug classes 5,14 and paralytics 1,6 to lower the dose of individual agents 5 or administering a low maintenance dose following a higher induction dose are typical strategies. However, despite its well-known potential cardiorespiratory toxicities, including death8, tricaine is still the most widely used, the best available, and the only anesthetic approved by the US Food and Drug Administration (FDA) for zebrafish anesthesia.…”

Section: Discussionmentioning

confidence: 99%

“…NOTE: Heart rate depends on several factors, including zebrafish age and strain, anesthesia agents (e.g., tricaine, isoflurane, etc.) and concentration, anesthesia usage (single agent 5,7 vs. combined agents 5 ) and exposure time 5 . For example, in this study the heart rate of 12–18 month-old wild-type AB zebrafish after 3–5 min of immersion in 0.02–0.04% tricaine solution was 116 ± 17 beats per minute ( n = 9), consistent with literature reports of heart rate for this age group and anesthetic 5,7 .…”

Section: Protocolmentioning

confidence: 99%

“…Nonetheless, the electrocardiogram (ECG) waveforms and the duration of the QT interval of both species are remarkably similar (Figure 1). Accordingly, zebrafish has emerged as a popular model for studying human inherited arrhythmias 1,2,3 and for high-throughput drug screening of potential human cardiotoxicities 4,5 , such as QT prolongation.…”

Section: Introductionmentioning

confidence: 99%

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In Vivo Surface Electrocardiography for Adult Zebrafish

Zhao

Yun

Nguyen

et al. 2019

JoVE

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The electrocardiogram waveforms of adult zebrafish and those of humans are remarkably similar. These electrocardiogram similarities enhance the value of zebrafish not only as a research model for human cardiac electrophysiology and myopathies but also as a surrogate model in high throughput pharmaceutical screening for potential cardiotoxicities to humans, such as QT prolongation. As such, in vivo electrocardiography for adult zebrafish is an electrical phenotyping tool that is necessary, if not indispensable, for cross-sectional or longitudinal in vivo electrophysiological characterizations. However, too often, the lack of a reliable, practical, and cost-effective recording method remains a major challenge preventing this in vivo diagnostic tool from becoming more readily accessible. Here, we describe a practical, straightforward approach to in vivo electrocardiography for adult zebrafish using a low-maintenance, cost-effective, and comprehensive system that yields consistent, reliable recordings. We illustrate our protocol using healthy adult male zebrafish of 12–18 months of age. We also introduce a rapid real-time interpretation strategy for quality validation to ensure data accuracy and robustness early in the electrocardiogram recording process.

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Section: Representative Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Protocolmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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In Vivo Surface Electrocardiography for Adult Zebrafish

Zhao

Yun

Nguyen

et al. 2019

JoVE

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“…Remarkably, about 70% of genes identified in the human reference genome have at least one obvious zebrafish orthologue and CVD associated genes in humans are conserved to a great extent compared to orthologous zebrafish genes [34,[43][44][45]. Hence, it comes as no surprise that a broad range of standard cardiovascular drugs for humans used in daily clinical practice has analogous effects on zebrafish heart and vessels underlining the usage of the zebrafish as an important animal model in cardiovascular research (Table 1) [26,[46][47][48][49][50][51][52][53][54].…”

Section: Modeling Human Cardiovascular Disorders Using the Zebrafishmentioning

confidence: 99%

Streamlining drug discovery assays for cardiovascular disease using zebrafish

Pott

Rottbauer

Just

2019

Expert Opinion on Drug Discovery

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Introduction: In the last decade, our armamentarium of cardiovascular drug therapy has expanded significantly. Using innovative functional genomics strategies such as genome editing by CRISPR/Cas9 as well as high-throughput assays to identify bioactive small chemical compounds has significantly facilitated elaboration of the underlying pathomechanism in various cardiovascular diseases. However, despite scientific progress approvals for cardiovascular drugs has stagnated significantly compared to other fields of drug discovery and therapy during the past years. Areas covered: In this review, the authors discuss the aspects and pitfalls during the early phase of cardiovascular drug discovery and describe the advantages of zebrafish as an in vivo organism to model human cardiovascular diseases (CVD) as well as an in vivo platform for high-throughput chemical compound screening. They also highlight the emerging, promising techniques of automated read-out systems during high-throughput screening (HTS) for the evaluation of important cardiac functional parameters in zebrafish with the potential to streamline CVD drug discovery. Expert opinion: The successful identification of novel drugs to treat CVD is a major challenge in modern biomedical and clinical research. In this context, the definition of the etiologic fundamentals of human cardiovascular diseases is the prerequisite for an efficient and straightforward drug discovery.

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