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dc.contributor.authorWalweel, K
dc.contributor.authorSkeggs, K
dc.contributor.authorBoon, AC
dc.contributor.authorSee Hoe, LE
dc.contributor.authorBouquet, M
dc.contributor.authorObonyo, NG
dc.contributor.authorPedersen, SE
dc.contributor.authorDiab, SD
dc.contributor.authorPassmore, MR
dc.contributor.authorHyslop, K
dc.contributor.authorWood, ES
dc.contributor.authorReid, J
dc.contributor.authorColombo, SM
dc.contributor.authorBartnikowski, NJ
dc.contributor.authorWells, MA
dc.contributor.authorBlack, D
dc.contributor.authorPimenta, LP
dc.contributor.authorStevenson, AK
dc.contributor.authorBisht, K
dc.contributor.authorMarshall, L
dc.contributor.authorPrabhu, DA
dc.contributor.authorJames, L
dc.contributor.authorPlatts, DG
dc.contributor.authorMacdonald, PS
dc.contributor.authorMcGiffin, DC
dc.contributor.authorSuen, JY
dc.contributor.authorFraser, JF
dc.date.accessioned2020-10-13T01:05:16Z
dc.date.available2020-10-13T01:05:16Z
dc.date.issued2020
dc.identifier.issn1423-0127
dc.identifier.doi10.1186/s12929-020-00690-7
dc.identifier.urihttp://hdl.handle.net/10072/398307
dc.description.abstractBackground: A lung transplant is the last resort treatment for many patients with advanced lung disease. The majority of donated lungs come from donors following brain death (BD). The endothelin axis is upregulated in the blood and lung of the donor after BD resulting in systemic inflammation, lung damage and poor lung graft outcomes in the recipient. Tezosentan (endothelin receptor blocker) improves the pulmonary haemodynamic profile; however, it induces adverse effects on other organs at high doses. Application of ex vivo lung perfusion (EVLP) allows the development of organ-specific hormone resuscitation, to maximise and optimise the donor pool. Therefore, we investigate whether the combination of EVLP and tezosentan administration could improve the quality of donor lungs in a clinically relevant 6-h ovine model of brain stem death (BSD). Methods: After 6 h of BSD, lungs obtained from 12 sheep were divided into two groups, control and tezosentan-treated group, and cannulated for EVLP. The lungs were monitored for 6 h and lung perfusate and tissue samples were processed and analysed. Blood gas variables were measured in perfusate samples as well as total proteins and pro-inflammatory biomarkers, IL-6 and IL-8. Lung tissues were collected at the end of EVLP experiments for histology analysis and wet-dry weight ratio (a measure of oedema). Results: Our results showed a significant improvement in gas exchange [elevated partial pressure of oxygen (P = 0.02) and reduced partial pressure of carbon dioxide (P = 0.03)] in tezosentan-treated lungs compared to controls. However, the lungs hematoxylin-eosin staining histology results showed minimum lung injuries and there was no difference between both control and tezosentan-treated lungs. Similarly, IL-6 and IL-8 levels in lung perfusate showed no difference between control and tezosentan-treated lungs throughout the EVLP. Histological and tissue analysis showed a non-significant reduction in wet/dry weight ratio in tezosentan-treated lung tissues (P = 0.09) when compared to control. Conclusions: These data indicate that administration of tezosentan could improve pulmonary gas exchange during EVLP.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherSpringer Science and Business Media LLC
dc.relation.ispartofissue1
dc.relation.ispartofjournalJournal of Biomedical Science
dc.relation.ispartofvolume27
dc.subject.fieldofresearchBiological Sciences
dc.subject.fieldofresearchInformation and Computing Sciences
dc.subject.fieldofresearchMedical and Health Sciences
dc.subject.fieldofresearchcode06
dc.subject.fieldofresearchcode08
dc.subject.fieldofresearchcode11
dc.subject.keywordsBrain stem death
dc.subject.keywordsEVLP
dc.subject.keywordsEndothelin axis
dc.subject.keywordsLung transplantation
dc.subject.keywordsTezosentan
dc.titleEndothelin receptor antagonist improves donor lung function in an ex vivo perfusion system
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationWalweel, K; Skeggs, K; Boon, AC; See Hoe, LE; Bouquet, M; Obonyo, NG; Pedersen, SE; Diab, SD; Passmore, MR; Hyslop, K; Wood, ES; Reid, J; Colombo, SM; Bartnikowski, NJ; Wells, MA; Black, D; Pimenta, LP; Stevenson, AK; Bisht, K; Marshall, L; Prabhu, DA; James, L; Platts, DG; Macdonald, PS; McGiffin, DC; Suen, JY; Fraser, JF, Endothelin receptor antagonist improves donor lung function in an ex vivo perfusion system., Journal of Biomedical Science, 2020, 27 (1)
dcterms.dateAccepted2020-09-24
dcterms.licensehttp://creativecommons.org/licenses/by/4.0/
dc.date.updated2020-10-12T05:03:32Z
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© 2020 The Authors. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.
gro.hasfulltextFull Text
gro.griffith.authorWells, Matt A.
gro.griffith.authorFraser, John F.
gro.griffith.authorSee Hoe, Louise


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