| Autor: |
Aadil Ali, Antti I. Nykanen, Erika Beroncal, Edson Brambate, Andrea Mariscal, Vinicius Michaelsen, Aizhou Wang, Mitsuaki Kawashima, Rafaela V.P. Ribeiro, Yu Zhang, Eddy Fan, Laurent Brochard, Jonathan Yeung, Tom Waddell, Mingyao Liu, Ana C. Andreazza, Shaf Keshavjee, Marcelo Cypel |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
EBioMedicine, Vol 83, Iss , Pp 104210- (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2352-3964 |
| DOI: |
10.1016/j.ebiom.2022.104210 |
| Popis: |
Summary: Background: Cold static preservation (CSP) at higher temperatures (10°C) has been recently shown as an optimal strategy up to 24-36h of preservation. Here, we hypothesized that alternating 10°C static storage with cycles of normothermic ex vivo lung perfusion (EVLP) would provide conditions for cellular “recharge”, allowing for multi-day lung preservation. Methods: Donor lungs from male Yorkshire pigs were preserved using 10°C CSP with two cycles of 4h EVLP. After a total of 3 days of preservation, a left lung transplant was performed followed by 4h of graft evaluation. As controls, 2 lungs were preserved solely with continuous 10°C preservation for 3 days and transplanted. Findings: For animals receiving lungs preserved using a cyclic EVLP protocol, lung function and histological structures were stable and the recipient systemic partial pressure of oxygen/fraction of inspired oxygen (P/F Ratio) after excluding the contralateral lung was 422 ± 61 mmHg. In contrast, lungs preserved solely in continuous cold static storage at 10°C for 72h developed massive lung failure, resulting in recipient death. Metabolomic analysis revealed that EVLP plays a critical role in the re-vitalization of key central carbon energy metabolites (Glucose, Succinate, N-Acetyl Aspartate) and reducing the expression of the inflammasome activation marker CASP1. Interpretation: In conclusion, we demonstrate for the first time the feasibility of 3-day lung preservation leading to excellent early post-transplant outcomes. The thoughtful combination of cold storage (10°C) and intermittent EVLP can open new opportunities in organ transplantation. Funding: This work was supported by the UHN Foundation (Grant#1013612). |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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