Contemporaneous 3D characterization of acute and chronic myocardial I/R injury and response
- Resource Type
- Original Paper
- Authors
- Merz, Simon F.; Korste, Sebastian; Bornemann, Lea; Michel, Lars; Stock, Pia; Squire, Anthony; Soun, Camille; Engel, Daniel R.; Detzer, Julia; Lörchner, Holger; Hermann, Dirk M.; Kamler, Markus; Klode, Joachim; Hendgen-Cotta, Ulrike B.; Rassaf, Tienush; Gunzer, Matthias; Totzeck, Matthias
- Source
- Nature Communications. 10(1)
- Subject
- Language
- English
- ISSN
- 2041-1723
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.
Detailed characterization of cardiac damage following ischemia/reperfusion injury and detection of occurring inflammatory responses is important for the development of new therapeutic concepts. Here the authors present a method for the three-dimensional investigation of acute and chronic cardiac injury responses using light sheet fluorescence microscopy.