Annexin v homodimer protects against ischemia reperfusion-induced acute lung injury in lung transplantation

Kohei Hashimoto, Hyunhee Kim, Hisashi Oishi, Manyin Chen, Ilker Iskender, Jin Sakamoto, Akihiro Ohsumi, Zehong Guan, David Hwang, Thomas K. Waddell, Marcelo Cypel, Mingyao Liu, Shaf Keshavjee

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Objective We hypothesized that administration of a homodimer of recombinant annexin V, diannexin, could shield phosphatidylserine on the endothelium, and inhibit leukocyte and platelet adhesion, thereby potentially reducing ischemia reperfusion injury (IRI) in lung transplantation. This hypothesis was tested using a rat syngeneic single left-lung transplant model. Methods Rats were randomly assigned to receive diannexin (DN group; n = 10) or normal saline (control group; n = 10). Diannexin (1000 μg/kg) was administered to the donor lung in the pulmonary flush solution, and to the recipient intravenously, 5 minutes after initiation of reperfusion. Grafts were reperfused for 2 hours. Results The transplanted grafts in the DN group performed significantly better in gas exchange with higher partial pressure of oxygen (control group: 179 ± 121 vs DN group: 330 ± 54 mm Hg; P =.007) and lower partial pressure of carbon dioxide (control: 55.1 ± 26 vs DN: 34.2 ± 11 mm Hg; P =.04), as well as lower peak airway pressure (control: 20.5 ± 8.5 vs DN: 12.0 ± 7.9 cm H2O; P =.035) after 2 hours of reperfusion. Wet-to-dry lung weight ratio (P =.054), and alveolar fibrin deposition score (P =.04), were reduced in the DN group. Caspase-cleaved cytokeratin 18 in plasma (a marker of epithelial apoptosis) was significantly reduced in the DN group (P =.013). Furthermore, gene-expression levels of proinflammatory cytokines in the transplanted graft, including interleukin-6 (P =.04) and macrophage inflammatory protein 2 (P =.03) were significantly decreased in the DN group. Conclusions A homodimer of recombinant annexin V reduced ischemia reperfusion injury in a lung transplant animal model, by reducing cell death and tissue inflammation.

Original languageEnglish
Pages (from-to)861-869
Number of pages9
JournalJournal of Thoracic and Cardiovascular Surgery
Volume151
Issue number3
DOIs
Publication statusPublished - 2016 Mar 1
Externally publishedYes

Keywords

  • apoptosis
  • diannexin
  • ischemia reperfusion injury
  • primary graft dysfunction

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

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  • Cite this

    Hashimoto, K., Kim, H., Oishi, H., Chen, M., Iskender, I., Sakamoto, J., Ohsumi, A., Guan, Z., Hwang, D., Waddell, T. K., Cypel, M., Liu, M., & Keshavjee, S. (2016). Annexin v homodimer protects against ischemia reperfusion-induced acute lung injury in lung transplantation. Journal of Thoracic and Cardiovascular Surgery, 151(3), 861-869. https://doi.org/10.1016/j.jtcvs.2015.10.112