• myGriffith
    • Staff portal
    • Contact Us⌄
      • Future student enquiries 1800 677 728
      • Current student enquiries 1800 154 055
      • International enquiries +61 7 3735 6425
      • General enquiries 07 3735 7111
      • Online enquiries
      • Staff phonebook
    View Item 
    •   Home
    • Griffith Research Online
    • Journal articles
    • View Item
    • Home
    • Griffith Research Online
    • Journal articles
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

  • All of Griffith Research Online
    • Communities & Collections
    • Authors
    • By Issue Date
    • Titles
  • This Collection
    • Authors
    • By Issue Date
    • Titles
  • Statistics

  • Most Popular Items
  • Statistics by Country
  • Most Popular Authors
  • Support

  • Contact us
  • FAQs
  • Admin login

  • Login
  • Endothelin receptor antagonist improves donor lung function in an ex vivo perfusion system

    Thumbnail
    View/Open
    Wells445696Published.pdf (825.3Kb)
    File version
    Version of Record (VoR)
    Author(s)
    Walweel, 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
    Griffith University Author(s)
    Wells, Matt A.
    Fraser, John F.
    See Hoe, Louise
    Year published
    2020
    Metadata
    Show full item record
    Abstract
    Background: 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 ...
    View more >
    Background: 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.
    View less >
    Journal Title
    Journal of Biomedical Science
    Volume
    27
    Issue
    1
    DOI
    https://doi.org/10.1186/s12929-020-00690-7
    Copyright Statement
    © 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.
    Subject
    Biological sciences
    Biomedical and clinical sciences
    Brain stem death
    EVLP
    Endothelin axis
    Lung transplantation
    Tezosentan
    Publication URI
    http://hdl.handle.net/10072/398307
    Collection
    • Journal articles

    Footer

    Disclaimer

    • Privacy policy
    • Copyright matters
    • CRICOS Provider - 00233E

    Tagline

    • Gold Coast
    • Logan
    • Brisbane - Queensland, Australia
    First Peoples of Australia
    • Aboriginal
    • Torres Strait Islander