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RESOURCE ARTICLE
A Langendorff-like system to quantify cardiac pump function in adult zebrafish
Hong Zhang, Alexey V. Dvornikov, Inken G. Huttner, Xiao Ma, Celine F. Santiago, Diane Fatkin, Xiaolei Xu
Disease Models & Mechanisms 2018 11: dmm034819 doi: 10.1242/dmm.034819 Published 10 September 2018
Hong Zhang
1Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55902, USA
2Cardiovascular Surgery Department, the Second Xiangya Hospital of Central South University, Changsha 410011, China
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Alexey V. Dvornikov
1Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55902, USA
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  • ORCID record for Alexey V. Dvornikov
  • For correspondence: dvornikov.alexey@mayo.edu xu.xiaolei@mayo.edu
Inken G. Huttner
3Molecular Cardiology Division, Victor Chang Cardiac Research Institute, Sydney, NSW 2010, Australia
4St. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2052, Australia
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Xiao Ma
1Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55902, USA
5Clinical and Translational Sciences Track, Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic College of Medicine and Science, Rochester, MN 55092, USA
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Celine F. Santiago
3Molecular Cardiology Division, Victor Chang Cardiac Research Institute, Sydney, NSW 2010, Australia
4St. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2052, Australia
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Diane Fatkin
3Molecular Cardiology Division, Victor Chang Cardiac Research Institute, Sydney, NSW 2010, Australia
4St. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2052, Australia
6Cardiology Department, St. Vincent's Hospital, Sydney, NSW 2010, Australia
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Xiaolei Xu
1Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55902, USA
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  • For correspondence: dvornikov.alexey@mayo.edu xu.xiaolei@mayo.edu
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ABSTRACT

Zebrafish are increasingly used as a vertebrate model to study human cardiovascular disorders. Although heart structure and function are readily visualized in zebrafish embryos because of their optical transparency, the lack of effective tools for evaluating the hearts of older, nontransparent fish has been a major limiting factor. The recent development of high-frequency echocardiography has been an important advance for in vivo cardiac assessment, but it necessitates anesthesia and has limited ability to study acute interventions. We report the development of an alternative experimental ex vivo technique for quantifying heart size and function that resembles the Langendorff heart preparations that have been widely used in mammalian models. Dissected adult zebrafish hearts were perfused with a calcium-containing buffer, and a beat frequency was maintained with electrical stimulation. The impact of pacing frequency, flow rate and perfusate calcium concentration on ventricular performance (including end-diastolic and end-systolic volumes, ejection fraction, radial strain, and maximal velocities of shortening and relaxation) were evaluated and optimal conditions defined. We determined the effects of age on heart function in wild-type male and female zebrafish, and successfully detected hypercontractile and hypocontractile responses after adrenergic stimulation or doxorubicin treatment, respectively. Good correlations were found between indices of cardiac contractility obtained with high-frequency echocardiography and with the ex vivo technique in a subset of fish studied with both methods. The ex vivo beating heart preparation is a valuable addition to the cardiac function tool kit that will expand the use of adult zebrafish for cardiovascular research.

Footnotes

  • Competing interests

    The authors declare no competing or financial interests.

  • Author contributions

    Conceptualization: A.V.D.; Methodology: H.Z., A.V.D., X.M.; Software: A.V.D.; Validation: H.Z., A.V.D., I.G.H., C.F.S.; Formal analysis: H.Z., A.V.D., C.F.S.; Investigation: H.Z., A.V.D., I.G.H., X.M., C.F.S.; Data curation: H.Z., A.V.D., I.G.H., X.M., C.F.S., D.F.; Writing - original draft: A.V.D., X.X.; Writing - review & editing: H.Z., A.V.D., I.G.H., D.F., X.X.; Supervision: D.F., X.X.; Project administration: A.V.D., I.G.H., D.F., X.X.; Funding acquisition: D.F., X.X.

  • Funding

    The work was supported by the National Heart, Lung, and Blood Institute (R01HL107304 and R01HL81753 to X.X.), the Mayo Foundation for Medical Education and Research (to X.X.), the National Health and Medical Research Council, the Estate of the Late RT Hall, St. Vincent's Clinic Foundation and the Simon Lee Foundation (to D.F.).

  • Supplementary information

    Supplementary information available online at http://dmm.biologists.org/lookup/doi/10.1242/dmm.034819.supplemental

  • Received April 4, 2018.
  • Accepted July 10, 2018.
  • © 2018. Published by The Company of Biologists Ltd
http://creativecommons.org/licenses/by/3.0

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

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Keywords

  • Cardiac contractility
  • Cardiac pump function
  • Langendorff
  • Zebrafish

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RESOURCE ARTICLE
A Langendorff-like system to quantify cardiac pump function in adult zebrafish
Hong Zhang, Alexey V. Dvornikov, Inken G. Huttner, Xiao Ma, Celine F. Santiago, Diane Fatkin, Xiaolei Xu
Disease Models & Mechanisms 2018 11: dmm034819 doi: 10.1242/dmm.034819 Published 10 September 2018
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RESOURCE ARTICLE
A Langendorff-like system to quantify cardiac pump function in adult zebrafish
Hong Zhang, Alexey V. Dvornikov, Inken G. Huttner, Xiao Ma, Celine F. Santiago, Diane Fatkin, Xiaolei Xu
Disease Models & Mechanisms 2018 11: dmm034819 doi: 10.1242/dmm.034819 Published 10 September 2018

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