Successful 3-day lung preservation using a cyclic normothermic ex vivo lung perfusion strategy

被引：25

作者：

Ali, Aadil ^{[1
]}

Nykanen, Antti I. ^{[1
]}

Beroncal, Erika ^{[2
,3
]}

Brambate, Edson ^{[1
]}

Mariscal, Andrea ^{[1
]}

Michaelsen, Vinicius ^{[1
]}

Wang, Aizhou ^{[1
]}

Kawashima, Mitsuaki ^{[1
]}

Ribeiro, Rafaela V. P. ^{[1
]}

Zhang, Yu ^{[1
]}

Fan, Eddy ^{[4
,5
]}

Brochard, Laurent ^{[4
,5
,6
,7
]}

Yeung, Jonathan ^{[1
,8
]}

Waddell, Tom ^{[1
,8
]}

Liu, Mingyao ^{[1
,8
]}

Andreazza, Ana C. ^{[2
,3
]}

Keshavjee, Shaf ^{[1
,8
]}

Cypel, Marcelo ^{[1
,8
,9
]}

机构：

[1] Univ Hlth Network, Toronto Gen Hosp Res Inst, Ajmera Transplant Ctr, Latner Thorac Surg Res Labs, Toronto, ON M5G 1L7, Canada

[2] Univ Toronto, Dept Pharmacol & Toxicol, Canada Mitochondrial Network, Toronto, ON M5S 1A8, Canada

[3] Univ Toronto, Dept Psychiat, Canada Mitochondrial Network, Toronto, ON M5S 1A8, Canada

[4] Univ Toronto, Univ Hlth Network, Div Respirol, Toronto, ON M5B 1W8, Canada

[5] Univ Toronto, Univ Hlth Network, Div Crit Care Med, Toronto, ON M5B 1W8, Canada

[6] Univ Toronto, St Michaels Hosp, Keenan Res Ctr, Unity Hlth Toronto, Toronto, ON M5B 1T8, Canada

[7] Univ Toronto, Interdept Div Crit Care Med, Toronto, ON M5B 1T8, Canada

[8] Univ Hlth Network, Univ Toronto, Toronto Lung Transplant Program, Div Thorac Surg,Dept Surg, Toronto, ON M5G 2C4, Canada

[9] Toronto Gen Hosp, 200 Elizabeth St,9N969, Toronto, ON M5G 2C4, Canada

来源：

EBIOMEDICINE | 2022年 / 83卷

关键词：

Ex vivo lung perfusion; Lung preservation; Lung transplant; Metabolomics; TRANSPLANTATION; INFLAMMASOME; METABOLISM; ISCHEMIA; QUALITY;

D O I：

10.1016/j.ebiom.2022.104210

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background Cold static preservation (CSP) at higher temperatures (10 degrees C) has been recently shown as an optimal strategy up to 24-36h of preservation. Here, we hypothesized that alternating 10 degrees 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 degrees 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 degrees 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 degrees 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 degrees C) and intermittent EVLP can open new opportunities in organ transplantation. Copyright (C) 2022 The Author(s). Published by Elsevier B.V.

引用

页数：13