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

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, Joachim Klode, Ulrike B. Hendgen-Cotta, Tienush Rassaf, Matthias Gunzer () and Matthias Totzeck ()
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Simon F. Merz: University Duisburg-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
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

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-10338-2

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