Pyrrolidine dithiocarbamate administered during ex-vivo lung perfusion promotes rehabilitation of injured donor rat lungs obtained after prolonged warm ischemia.

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State: Public
Version: Final published version
License: Not specified
Serval ID
serval:BIB_B3922CED6696
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Pyrrolidine dithiocarbamate administered during ex-vivo lung perfusion promotes rehabilitation of injured donor rat lungs obtained after prolonged warm ischemia.
Journal
PloS one
Author(s)
Francioli C., Wang X., Parapanov R., Abdelnour E., Lugrin J., Gronchi F., Perentes J., Eckert P., Ris H.B., Piquilloud L., Krueger T. (co-last), Liaudet L.
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Publication state
Published
Issued date
2017
Peer-reviewed
Oui
Volume
12
Number
3
Pages
e0173916
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Damaged lung grafts obtained after circulatory death (DCD lungs) and warm ischemia may be at high risk of reperfusion injury after transplantation. Such lungs could be pharmacologically reconditioned using ex-vivo lung perfusion (EVLP). Since acute inflammation related to the activation of nuclear factor kappaB (NF-κB) is instrumental in lung reperfusion injury, we hypothesized that DCD lungs might be treated during EVLP by pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-κB. Rat lungs exposed to 1h warm ischemia and 2 h cold ischemia were subjected to EVLP during 4h, in absence (CTRL group, N = 6) or in presence of PDTC (2.5g/L, PDTC group, N = 6). Static pulmonary compliance (SPC), peak airway pressure (PAWP), pulmonary vascular resistance (PVR), and oxygenation capacity were determined during EVLP. After EVLP, we measured the weight gain of the heart-lung block (edema), and the concentration of LDH (cell damage), proteins (permeability edema) and of the cytokines IL-6, TNF-α and CINC-1 in bronchoalveolar lavage (BAL), and we evaluated NF-κB activation by the degree of phosphorylation and degradation of its inhibitor IκBα in lung tissue. In CTRL, we found significant NF-κB activation, lung edema, and a massive release of LDH, proteins and cytokines. SPC significantly decreased, PAWP and PVR increased, while oxygenation tended to decrease. Treatment with PDTC during EVLP inhibited NF-κB activation, did not influence LDH release, but markedly reduced lung edema and protein concentration in BAL, suppressed TNFα and IL-6 release, and abrogated the changes in SPC, PAWP and PVR, with unchanged oxygenation. In conclusion, suppression of innate immune activation during EVLP using the NF-κB inhibitor PDTC promotes significant improvement of damaged rat DCD lungs. Future studies will determine if such rehabilitated lungs are suitable for in vivo transplantation.
Keywords
Animals, Antioxidants/administration & dosage, Bronchoalveolar Lavage Fluid/immunology, Cytokines/metabolism, Disease Models, Animal, Immunity, Innate/drug effects, In Vitro Techniques, Lung/immunology, Lung/physiopathology, Lung Injury/immunology, Lung Injury/physiopathology, Lung Injury/rehabilitation, Lung Transplantation/adverse effects, Lung Transplantation/methods, Male, NF-kappa B/antagonists & inhibitors, Perfusion, Pyrrolidines/administration & dosage, Rats, Rats, Sprague-Dawley, Reperfusion Injury/immunology, Reperfusion Injury/physiopathology, Reperfusion Injury/rehabilitation, Thiocarbamates/administration & dosage, Tissue Donors, Tissue and Organ Procurement, Transplantation Immunology, Warm Ischemia/adverse effects
Pubmed
Web of science
Open Access
Yes
Create date
28/03/2017 16:46
Last modification date
30/06/2023 5:54
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