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Contemporaneous 3D characterization of acute and chronic myocardial I/R injury and response

Author

Listed:
  • Simon F. Merz

    (University Duisburg-Essen
    University Hospital Essen)

  • Sebastian Korste

    (University Hospital Essen)

  • Lea Bornemann

    (University Duisburg-Essen)

  • Lars Michel

    (University Hospital Essen)

  • Pia Stock

    (University Hospital Essen)

  • Anthony Squire

    (University Duisburg-Essen)

  • Camille Soun

    (University Duisburg-Essen)

  • Daniel R. Engel

    (University Duisburg-Essen)

  • Julia Detzer

    (Max Planck Institute for Heart and Lung Research)

  • Holger Lörchner

    (Max Planck Institute for Heart and Lung Research
    Partner site Rhine-Main)

  • Dirk M. Hermann

    (University Hospital Essen)

  • Markus Kamler

    (University Hospital Essen)

  • Joachim Klode

    (University Hospital Essen)

  • Ulrike B. Hendgen-Cotta

    (University Hospital Essen)

  • Tienush Rassaf

    (University Hospital Essen)

  • Matthias Gunzer

    (University Duisburg-Essen)

  • Matthias Totzeck

    (University Hospital Essen)

Abstract

Cardioprotection by salvage of the infarct-affected myocardium is an unmet yet highly desired therapeutic goal. To develop new dedicated therapies, experimental myocardial ischemia/reperfusion (I/R) injury would require methods to simultaneously characterize extent and localization of the damage and the ensuing inflammatory responses in whole hearts over time. Here we present a three-dimensional (3D), simultaneous quantitative investigation of key I/R injury-components by combining bleaching-augmented solvent-based non-toxic clearing (BALANCE) using ethyl cinnamate (ECi) with light sheet fluorescence microscopy. This allows structural analyses of fluorescence-labeled I/R hearts with exceptional detail. We discover and 3D-quantify distinguishable acute and late vascular I/R damage zones. These contain highly localized and spatially structured neutrophil infiltrates that are modulated upon cardiac healing. Our model demonstrates that these characteristic I/R injury patterns can detect the extent of damage even days after the ischemic index event hence allowing the investigation of long-term recovery and remodeling processes.

Suggested Citation

  • Simon F. Merz & Sebastian Korste & Lea Bornemann & Lars Michel & Pia Stock & Anthony Squire & Camille Soun & Daniel R. Engel & Julia Detzer & Holger Lörchner & Dirk M. Hermann & Markus Kamler & Joachi, 2019. "Contemporaneous 3D characterization of acute and chronic myocardial I/R injury and response," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10338-2
    DOI: 10.1038/s41467-019-10338-2
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    Cited by:

    1. Zülal Cibir & Jacqueline Hassel & Justin Sonneck & Lennart Kowitz & Alexander Beer & Andreas Kraus & Gabriel Hallekamp & Martin Rosenkranz & Pascal Raffelberg & Sven Olfen & Kamil Smilowski & Roman Bu, 2023. "ComplexEye: a multi-lens array microscope for high-throughput embedded immune cell migration analysis," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

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