Successful 3-day lung preservation using a cyclic normothermic ex vivo lung perfusion strategy.
EBioMedicine
; 83: 104210, 2022 Sep.
Article
en En
| MEDLINE
| ID: mdl-35952495
ABSTRACT
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).Palabras clave
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Base de datos:
MEDLINE
Asunto principal:
Preservación de Órganos
/
Inflamasomas
Idioma:
En
Revista:
EBioMedicine
Año:
2022
Tipo del documento:
Article