International Journal of Molecular Sciences

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Dear Colleagues,

Organ transplantation (TX) is the best treatment for end-stage organ failure. However, the clinical needs outweigh the number of organs available, leading to significant and crucial organ shortage and forcing clinicians to use higher-risk organs for TX, such as Extended Criteria Donors (ECD), which are very vulnerable to ischemia-reperfusion injury (IRI) associated with TX.

IRI is the sum of damages accumulated during the complex TX process that originated from the deprivation of oxygen to the organ (in donor) and its subsequent restoration (in the recipient), including organ retrieval, static preservation, ex vivo dynamic perfusion and graft reperfusion. In all these steps, a “pleiade” of specific physiopathological mechanisms at a molecular level affects the organ's post-transplant function in the short and long term, which should be explored in depth.

This special IJMS issue draws attention to new static preservation and dynamic perfusion machine strategies (HOPE and NMP) to increase organ protection, based on new pharmacological treatments, including single-cell transcriptomics and mi-RNAs. Overall therapeutic targets would allow a better understanding of the underlying molecular pathophysiology mechanisms involved in clinical and experimental transplantation scenarios when marginal organs are specially used, such as steatotic livers.

Prof. Dr. Joan Roselló-Catafau
Dr. Arnau Panisello-Roselló
Dr. Teresa Carbonell Camós
Guest Editors

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Keywords

organ (liver, pancreas, intestine, kidney) transplantation
ischemia-reperfusion injury
“ex vivo” static preservation and dynamic machine perfusion strategies
mitochondria
pharmacological treatments
mi-RNAs
redox-stress
inflammatory mediators
cell lines

Published Papers (1 paper)

Research

13 pages, 2103 KiB

Open AccessArticle

Ex Vivo Optimization of Donor Lungs with Inhaled Sevoflurane during Normothermic Ex Vivo Lung Perfusion (VITALISE): A Pilot and Feasibility Study in Sheep

by Timo Steinkühler, Shuqi Yang, Michiel A. Hu, Jayant S. Jainandunsing, Neeltina M. Jager, Michiel E. Erasmus, Michel M. R. F. Struys, Dirk J. Bosch, Matijs van Meurs, Matthieu Jabaudon, Damien Richard, Wim Timens, Henri G. D. Leuvenink and Gertrude J. Nieuwenhuijs-Moeke

Int. J. Mol. Sci. 2024, 25(4), 2413; https://doi.org/10.3390/ijms25042413 - 19 Feb 2024

Viewed by 928

Abstract

Volatile anesthetics have been shown in different studies to reduce ischemia reperfusion injury (IRI). Ex vivo lung perfusion (EVLP) facilitates graft evaluation, extends preservation time and potentially enables injury repair and improvement of lung quality. We hypothesized that ventilating lungs with sevoflurane during EVLP would reduce lung injury and improve lung function. We performed a pilot study to test this hypothesis in a slaughterhouse sheep DCD model. Lungs were harvested, flushed and stored on ice for 3 h, after which EVLP was performed for 4 h. Lungs were ventilated with either an FiO₂ of 0.4 (EVLP, n = 5) or FiO₂ of 0.4 plus sevoflurane at a 2% end-tidal concentration (C_et) (S-EVLP, n = 5). Perfusate, tissue samples and functional measurements were collected and analyzed. A steady state of the target C_et sevoflurane was reached with measurable concentrations in perfusate. Lungs in the S-EVLP group showed significantly better dynamic lung compliance than those in the EVLP group (p = 0.003). Oxygenation capacity was not different in treated lungs for delta partial oxygen pressure (PO₂; +3.8 (−4.9/11.1) vs. −11.7 (−12.0/−3.2) kPa, p = 0.151), but there was a trend of a better PO₂/FiO₂ ratio (p = 0.054). Perfusate ASAT levels in S-EVLP were significantly reduced compared to the control group (198.1 ± 93.66 vs. 223.9 ± 105.7 IU/L, p = 0.02). We conclude that ventilating lungs with sevoflurane during EVLP is feasible and could be useful to improve graft function. Full article

(This article belongs to the Special Issue Recent Advancements in Organ Transplantation: From Organ Protection to Molecular Therapy)

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