Functional Assessment of Cardiac Responses of Adult Zebrafish (Danio rerio) to Acute and Chronic Temperature Change Using High-Resolution Echocardiography

Lee, Ling; Genge, Christine E.; Cua, Michelle; Sheng, Xiaoye; Rayani, Kaveh; Beg, Mirza Faisal; Sarunic, Marinko V.; Tibbits, Glen F.

doi:10.1371/journal.pone.0145163

Cited by 35 publications

(41 citation statements)

References 52 publications

(68 reference statements)

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“…Hand2 plays a role in cardiac differentiation and morphogenesis (Trinh et al, 2005;Garavito-Aguilar et al, 2010), whereas Nkx2.5 maintains cardiac chamber identity (Targoff et al, 2008;Targoff et al, 2013). More recently, cardiac contraction and resulting fluid forces were shown to activate Notch signaling to modulate cardiac trabeculation in Zebrafish (Samsa et al, 2015;Lee et al, 2016b).…”

Section: Zebrafish Heart Developmentmentioning

confidence: 99%

Heart function and hemodynamic analysis for zebrafish embryos

Yalcin

Amindari

Butcher

et al. 2017

Developmental Dynamics

130

100

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The Zebrafish has emerged to become a powerful vertebrate animal model for cardiovascular research in recent years. Its advantages include easy genetic manipulation, transparency, small size, low cost, and the ability to survive without active circulation at early stages of development. Sequencing the whole genome and identifying ortholog genes with human genome made it possible to induce clinically relevant cardiovascular defects via genetic approaches. Heart function and disturbed hemodynamics need to be assessed in a reliable manner for these disease models in order to reveal the mechanobiology of induced defects. This effort requires precise determination of blood flow patterns as well as hemodynamic stress (i.e., wall shear stress and pressure) levels within the developing heart. While traditional approach involves time-lapse brightfield microscopy to track cell and tissue movements, in more recent studies fast light-sheet fluorescent microscopes are utilized for that purpose. Integration of more complicated techniques like particle image velocimetry and computational fluid dynamics modeling for hemodynamic analysis holds a great promise to the advancement of the Zebrafish studies. Here, we discuss the latest developments in heart function and hemodynamic analysis for Zebrafish embryos and conclude with our future perspective on dynamic analysis of the Zebrafish cardiovascular system. Developmental Dynamics 246:868-880, 2017. V C 2017 Wiley Periodicals, Inc.

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Section: Zebrafish Heart Developmentmentioning

confidence: 99%

Heart function and hemodynamic analysis for zebrafish embryos

Yalcin

Amindari

Butcher

et al. 2017

Developmental Dynamics

130

100

View full text Add to dashboard Cite

show abstract

“…As aerobic capacity and metabolic rate are directly interrelated with ambient temperature, incremental warming ( Figure 5) can be applied as physical stressor in ectothermic medaka and zebrafish embryos, which regulate cardiac output in response to temperature primarily through adaption of heart rate rather than stroke volume 50,51 .…”

Section: Discussionmentioning

confidence: 99%

Automated high-throughput heart rate measurement in medaka and zebrafish embryos under physiological conditions

Gierten

Pylatiuk

Hammouda

et al. 2019

Preprint

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Rationale: Accurate and efficient quantification of heartbeats in small fish models is an important readout to study cardiovascular biology, disease states and pharmacology at large scale. However, dependence on anesthesia, laborious sample orientation or requirement for fluorescent reporters have hampered the establishment of high-throughput heartbeat analysis.Objective: To overcome these limitations, we aimed to develop a high-throughput assay with automated heart rate scoring in medaka (Oryzias latipes) and zebrafish (Danio rerio) embryos under physiological conditions designed for genetic screens and drug discovery and validation. Methods and Results:We established an efficient screening assay employing automated label-free heart rate determination of randomly oriented, non-anesthetized specimen in microtiter plates. Automatically acquired bright-field data feeds into an easy-to-use HeartBeat software, a MATLAB algorithm with graphical user interface developed for automated quantification of heart rate and rhythm. Sensitivity of the assay and algorithm was demonstrated by profiling heart rates during entire embryonic development. Our analysis pipeline revealed acute temperature changes triggering rapid adaption of heart rates, which has implications for standardization of experimental layout. The approach is scalable and allows scoring of multiple embryos per well resulting in a throughput of >500 embryos per 96-well plate. In a proof of principle screen for compound testing, our assay captured concentration-dependent effects of nifedipine and terfenadine over time. Conclusion:A novel workflow and HeartBeat software provide efficient means for reliable and direct quantification of heart rate and rhythm of small fish in a physiological environment. Importantly, confounding factors such as anesthetics or laborious mounting are eliminated. We provide detailed profiles of embryonic heart rate dynamics in medaka and zebrafish as reference for future assay development. Ease of sample handling, automated imaging, physiological conditions and softwareassisted analysis now facilitate various large-scale applications ranging from phenotypic screening, interrogation of gene functions to cardiovascular drug development pipelines.

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“…Indeed, several studies have used high frequency echocardiography, often combined with doppler echography, to assess mechanical and hemodynamic heart function in adult zebrafish. [11][12][13][14][15] In this study, a microultrasound catheter designed for intravascular imaging of human subjects has been used to image the zebrafish heart. The microprobe of the IVUS system is easy to manipulate and can be placed on top of the visually beating thoracic area with ease.…”

Section: Discussionmentioning

confidence: 99%

“…This represents a limitation of this device in comparison with previous publications, where all parts of the hearts were observed. [10][11][12]14 We suspect that our microprobe is too narrow to allow a full coverage of the whole heart.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, it has been shown that a decrease of 10°in temperature can lead to a decrease of 50% in heart rate of zebrafish. 14 Overall, despite the aforementioned limitations, the use of a microprobe for intracoronary imaging in humans can easily be used to evaluate ventricle size and function in adult zebrafish and could be an alternative to other more expensive echocardiography devices. 11,14,18 Although echocardiography has been used to assess the heart of zebrafish, we are the first to report the use of coronary ultrasound probes, designed for humans, in the adult zebrafish.…”

Section: Discussionmentioning

confidence: 99%

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Use of Coronary Ultrasound Imaging to Evaluate Ventricular Function in Adult Zebrafish

et al. 2016

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So far, imaging of the adult zebrafish heart and assessment of heart failure in adult zebrafish have been very limited. Here, we describe a new method for in vivo imaging of the hypertrabeculated heart of the adult zebrafish using miniaturized cardiac ultrasound catheters obtained from the cardiac catheterization laboratory. This method allows the observation of the ventricle of zebrafish and the assessment of ventricular diameters during diastole and systole, as well as heart rate and fractional shortening. Significant changes in these parameters were detected through the use of an adult zebrafish heart failure model induced by chronic anemia. This imaging technique opens the door to detailed in vivo analysis of the adult heart failure phenotype in zebrafish.

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Functional Assessment of Cardiac Responses of Adult Zebrafish (Danio rerio) to Acute and Chronic Temperature Change Using High-Resolution Echocardiography

Cited by 35 publications

References 52 publications

Heart function and hemodynamic analysis for zebrafish embryos

Heart function and hemodynamic analysis for zebrafish embryos

Automated high-throughput heart rate measurement in medaka and zebrafish embryos under physiological conditions

Use of Coronary Ultrasound Imaging to Evaluate Ventricular Function in Adult Zebrafish

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