Mitochondrial transplantation enhances murine lung viability and recovery after ischemia-reperfusion injury
| Autor: | David Blitzer, Jerusha K. Thedsanamoorthy, James A. H. Inkster, Rouan Yao, Kaifeng Liu, Kamila Moskowitzova, Alan B. Packard, Alvise Guariento, Douglas B. Cowan, Borami Shin, Giovanna Ramirez-Barbieri, Ilias P. Doulamis, Arzoo Orfany, James D. McCully, Pedro J. del Nido, Khadija Iken, Gary A. Visner, Erin Snay |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Pulmonary and Respiratory Medicine acute lung injury ischemia-reperfusion injury mitochondrial transplantation Male Pathology medicine.medical_specialty Physiology Acute Lung Injury Ischemia Apoptosis 030204 cardiovascular system & hematology Lung injury 03 medical and health sciences Mice 0302 clinical medicine Physiology (medical) Medicine Animals Lung business.industry Cell Biology medicine.disease Mitochondria Respiratory Function Tests Transplantation Mice Inbred C57BL Disease Models Animal 030104 developmental biology Murine lung Neutrophil Infiltration Reperfusion Injury Cytokines Chemokines business Reperfusion injury Bronchoalveolar Lavage Fluid |
| Zdroj: | American journal of physiology. Lung cellular and molecular physiology. 318(1) |
| ISSN: | 1522-1504 |
| Popis: | The most common cause of acute lung injury is ischemia-reperfusion injury (IRI), during which mitochondrial damage occurs. We have previously demonstrated that mitochondrial transplantation is an efficacious therapy to replace or augment mitochondria damaged by IRI, allowing for enhanced muscle viability and function in cardiac tissue. Here, we investigate the efficacy of mitochondrial transplantation in a murine lung IRI model using male C57BL/6J mice. Transient ischemia was induced by applying a microvascular clamp on the left hilum for 2 h. Upon reperfusion mice received either vehicle or vehicle-containing mitochondria either by vascular delivery (Mito V) through the pulmonary artery or by aerosol delivery (Mito Neb) via the trachea (nebulization). Sham control mice underwent thoracotomy without hilar clamping and were ventilated for 2 h before returning to the cage. After 24 h recovery, lung mechanics were assessed and lungs were collected for analysis. Our results demonstrated that at 24 h of reperfusion, dynamic compliance and inspiratory capacity were significantly increased and resistance, tissue damping, elastance, and peak inspiratory pressure (Mito V only) were significantly decreased ( P < 0.05) in Mito groups as compared with their respective vehicle groups. Neutrophil infiltration, interstitial edema, and apoptosis were significantly decreased ( P < 0.05) in Mito groups as compared with vehicles. No significant differences in cytokines and chemokines between groups were shown. All lung mechanics results in Mito groups except peak inspiratory pressure in Mito Neb showed no significant differences ( P > 0.05) as compared with Sham. These results conclude that mitochondrial transplantation by vascular delivery or nebulization improves lung mechanics and decreases lung tissue injury. |
| Databáze: | OpenAIRE |
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