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Lung transplantation-induced cold ischemia–reperfusion injury in the murine lung

ABSTRACT: Cold ischemia-reperfusion induced injury contributes to poor lung transplant outcomes. We used transcriptome sequencing to study the biological response of mouse lungs to the cold ischemia-reperfusion process. Mouse orthotopic left LTx was performed with standard cuff techniques. Briefly, the donor lungs were recovered after being flushed with 10ml low potassium dextran (LPD) solution and inflated with 50% oxygen. Cold ischemia was induced by storing donor lungs in 20ml LPD at 4°C for 24 hours. Then, the left donor lung was cuffed and implanted into recipients within 45 minutes. After the 4-hour reperfusion, the recipient mice were sacrificed and the transplanted lungs were collected.

ORGANISM(S): Mus musculus

PROVIDER: GSE222957 | GEO | 2023/01/20

REPOSITORIES: GEO

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Macrophage infiltration induced by donor hypovolemia protects against severe primary graft dysfunction in mouse lung transplantation

Project description:BACKGROUND: Hypovolemia is common in lung donors before or after brain death. However, its impact on primary graft function (PGD) remains obscure. METHODS: A clinically relevant two-hit model of PGD was established by integrating hypovolemic shock (HS) and cold ischemia-reperfusion in a mouse model of orthotopic lung transplantation (LTx) from C57BL/6 to Balb/c. At -48 hours, HS was induced to donor by withdrawal of blood from femoral artery and keeping the mean arterial pressure at 15±5 mmHg for 4 h. At -24 hours, donor lungs were retrieved from mice with or without HS and stored at 0ºC until transplantation. CD11b-DTR mice were used as donor and treated with Diphtheria Toxin (DT) to deplete graft-infiltrating macrophages. RESULTS: HS mainly caused macrophage-predominant infiltration around pulmonary artery injury systemic inflammatory response, but little impairment of lung function even if in combination with cold ischemia-reperfusion. Transcriptional profiling showed HS pretreatment increased pulmonary damage and alveolar remodeling but ameliorated inflammatory infiltration when compared to one-hit model of 12 hours cold ischemia-reperfusion injury. The allografts with donor DT-treatment one day ahead of HS showed injury and dysfunction at donation and worsened further at 24 hours reperfusion, whereas the allografts with recipient DT-treatment immediately after transplantation showed similar function and histology to the control treated with saline. CONCLUSION: Donor hypovolemia causes pulmonary artery injury and infiltration but has little impact on allograft function, even in combination with 24 h cold ischemia. Graft-infiltrating macrophages are critical in protecting graft from HS-induced injury and cold ischemia-reperfusion injury.

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Expression of Human Lung Before and After Ex Vivo Lung Perfusion

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Expression data from donor lungs of cardiac death and brain death donors (re-analysis)

Project description:Ischemia reperfusion induced injury contributes to poor lung transplant outcomes.Microarrays were used to study the biological response of human lungs to the ischemia reperfusion process. Samples were collected from lung transplant cases at Toronto General Hospital. Lungs were donation after brain death (DBD)

2023-09-18 | GSE127242 | GEO

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Project description:Ischemia reperfusion induced injury contributes to poor lung transplant outcomes. We used microarrays to study the biological response of human lungs to the ischemia reperfusion process. Samples were collected from lung transplant cases at Toronto General Hospital. Lungs were donation after brain death (DBD)

2020-06-22 | GSE127003 | GEO

IL1β-dependent extravasation of pre-existing lung-restricted autoantibodies activates complement to promote primary graft dysfunction

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2022-10-19 | GSE211501 | GEO

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