Organotypic lung culture: A new model for studying ischemia and ex vivo perfusion in lung transplantation
Autor: | Jean-Marc Baste, Arnaud Gay, Hassiba Smail, Romain Noël, Michael Bubenheim, Hugues Begueret, Jean-Paul Morin, Pierre-Yves Litzler |
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Rok vydání: | 2015 |
Předmět: |
Pulmonary and Respiratory Medicine
Male Pathology medicine.medical_specialty medicine.medical_treatment Clinical Biochemistry Ischemia Biology Lesion Organ Culture Techniques In vivo medicine Lung transplantation Animals Warm Ischemia Rats Wistar Molecular Biology Lung Glutathione Peroxidase Histology medicine.disease In vitro Rats Perfusion medicine.anatomical_structure medicine.symptom Energy Metabolism Reactive Oxygen Species Lung Transplantation |
Zdroj: | Experimental lung research. 41(10) |
ISSN: | 1521-0499 |
Popis: | Donors after cardiac death (DCD) in lung transplantation is considered as a solution for organ shortage. However, it is characterized by warm ischemic period, which could be involved in severe Ischemia-Reperfusion lesion (IR) with early graft dysfunction. We describe a new hybrid model combining in vivo ischemia followed by in vitro reoxygenation using organ-specific culture.A hybrid model using in vivo ischemic period followed by in vitro lung slice reoxygenation was set up in rat to mimic DCD in lung transplantation with in vitro perfusion. Different markers (bioenergetics, oxidant stress assays, and histology) were measured to evaluate the viability of lung tissue after different ischemic times (I-0, I-1, I-2, I-4, I-15 hours) and reoxygenation times (R-0, R-1, R-4, R-24 hours).No differences were found in cell viability, ATP concentrations, extracellular LDH assays or histology, demonstrating extensive viability of up to 4 hours in lung tissue warm ischemia. We found oxidative stress mainly during the ischemic period with no burst at reoxygenation. Cytosolic anti-oxidant system was involved first (I-0,I-1,I-2) followed by mitochondrial anti-oxidant system for extensive ischemia (I-4). Histological features showed differences in this model of ischemia-reoxygenation between bronchial epithelium and lung parenchymal cells, with epithelium regeneration after 2 hours of warm ischemia and 24 hours of perfusion.The results of our hybrid model experiment suggest extensive lung viability of up to 4 hours ischemia. Our model could be an interesting tool to evaluate ex vivo reconditioning techniques after different in vivo lung insults. |
Databáze: | OpenAIRE |
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