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Contemporaneous 3D characterization of acute and chronic myocardial I/R injury and response
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...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6534576/ https://www.ncbi.nlm.nih.gov/pubmed/31127113 http://dx.doi.org/10.1038/s41467-019-10338-2 |
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author | 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 |
author_facet | 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 |
author_sort | Merz, Simon F. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6534576 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-65345762019-05-28 Contemporaneous 3D characterization of acute and chronic myocardial I/R injury and response 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 Nat Commun Article 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. Nature Publishing Group UK 2019-05-24 /pmc/articles/PMC6534576/ /pubmed/31127113 http://dx.doi.org/10.1038/s41467-019-10338-2 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article 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 Contemporaneous 3D characterization of acute and chronic myocardial I/R injury and response |
title | Contemporaneous 3D characterization of acute and chronic myocardial I/R injury and response |
title_full | Contemporaneous 3D characterization of acute and chronic myocardial I/R injury and response |
title_fullStr | Contemporaneous 3D characterization of acute and chronic myocardial I/R injury and response |
title_full_unstemmed | Contemporaneous 3D characterization of acute and chronic myocardial I/R injury and response |
title_short | Contemporaneous 3D characterization of acute and chronic myocardial I/R injury and response |
title_sort | contemporaneous 3d characterization of acute and chronic myocardial i/r injury and response |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6534576/ https://www.ncbi.nlm.nih.gov/pubmed/31127113 http://dx.doi.org/10.1038/s41467-019-10338-2 |
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