OXIDATIVE study: A pilot prospective observational cohort study protocol examining the influence of peri-reperfusion hyperoxemia and immune dysregulation on early allograft dysfunction after orthotopic liver transplantation.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read Online Read More Add to Saved list
  • Additional Information
    • Source:
      Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
    • Publication Information:
      Original Publication: San Francisco, CA : Public Library of Science
    • Subject Terms:
      Liver Transplantation*/adverse effects ; Liver Failure*; Humans ; Adolescent ; Prospective Studies ; Risk Factors ; Graft Survival ; Liver/metabolism ; Cohort Studies ; Allografts ; Reperfusion ; Oxygen/metabolism ; Observational Studies as Topic
    • Abstract:
      Early allograft dysfunction (EAD) is a functional hepatic insufficiency within a week of orthotopic liver transplantation (OLT) and is associated with morbidity and mortality. The etiology of EAD is multifactorial and largely driven by ischemia reperfusion injury (IRI), a phenomenon characterized by oxygen scarcity followed by paradoxical oxidative stress and inflammation. With the expanded use of marginal allografts more susceptible to IRI, the incidence of EAD may be increasing. This necessitates an in-depth understanding of the innate molecular mechanisms underlying EAD and interventions to mitigate its impact. Our central hypothesis is peri-reperfusion hyperoxemia and immune dysregulation exacerbate IRI and increase the risk of EAD. We will perform a pilot prospective single-center observational cohort study of 40 patients. The aims are to determine (1) the association between peri-reperfusion hyperoxemia and EAD and (2) whether peri-reperfusion perturbed cytokine, protein, and hypoxia inducible factor-1 alpha (HIF-1α) levels correlate with EAD after OLT. Inclusion criteria include age ≥ 18 years, liver failure, and donation after brain or circulatory death. Exclusion criteria include living donor donation, repeat OLT within a week of transplantation, multiple organ transplantation, and pregnancy. Partial pressure of arterial oxygen (PaO2) as the study measure allows for the examination of oxygen exposure within the confines of existing variability in anesthesiologist-administered fraction of inspired oxygen (FiO2) and the inclusion of patients with intrapulmonary shunting. The Olthoff et al. definition of EAD is the primary outcome. Secondary outcomes include postoperative acute kidney injury, pulmonary and biliary complications, surgical wound dehiscence and infection, and mortality. The goal of this study protocol is to identify EAD contributors that could be targeted to attenuate its impact and improve OLT outcomes. If validated, peri-reperfusion hyperoxemia and immune perturbations could be targeted via FiO2 titration to a goal PaO2 and/or administration of an immunomodulatory agent by the anesthesiologist intraoperatively.
      Competing Interests: The authors have declared that no competing interests exist.
      (Copyright: © 2024 Wilson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
    • References:
      Am J Physiol Gastrointest Liver Physiol. 2008 Oct;295(4):G823-32. (PMID: 18772364)
      Am J Transplant. 2011 Sep;11(9):1773-84. (PMID: 21672146)
      Mol Cell. 2008 May 23;30(4):393-402. (PMID: 18498744)
      Gastroenterol Hepatol (N Y). 2011 May;7(5):302-7. (PMID: 21857831)
      J Biomed Res. 2019 Jul 28;33(4):221-234. (PMID: 32383437)
      Cancer Res. 2008 Apr 15;68(8):2850-60. (PMID: 18413753)
      Yonsei Med J. 2017 May;58(3):489-496. (PMID: 28332352)
      J Hepatol. 2019 Apr;70(4):658-665. (PMID: 30582980)
      Liver Transpl. 2011 Mar;17(3):324-30. (PMID: 21384515)
      J Biol Chem. 2007 Oct 19;282(42):30544-52. (PMID: 17726031)
      Hepatol Commun. 2020 Dec 05;5(3):526-537. (PMID: 33681684)
      J Hepatol. 2013 Nov;59(5):1094-106. (PMID: 23811302)
      Hepatology. 1992 Aug;16(2):454-61. (PMID: 1639355)
      Dig Liver Dis. 2022 Aug;54(8):1076-1083. (PMID: 34965904)
      Anesth Analg. 2012 Oct;115(4):849-54. (PMID: 22798533)
      Am J Transplant. 2014 Jul;14(7):1481-7. (PMID: 24909061)
      Hepatology. 1995 Apr;21(4):1138-43. (PMID: 7705789)
      Hepatology. 1993 May;17(5):915-23. (PMID: 8387952)
      Transplant Proc. 2006 Oct;38(8):2488-91. (PMID: 17097977)
      Clin Transplant. 2022 Oct;36(10):e14613. (PMID: 35147248)
      JCI Insight. 2016 Dec 8;1(20):e89679. (PMID: 27942590)
      Int J Mol Sci. 2016 Sep 20;17(9):. (PMID: 27657051)
      Liver Transpl. 2010 Aug;16(8):943-9. (PMID: 20677285)
      Br J Anaesth. 2014 Jul;113 Suppl 1:i74-i81. (PMID: 24860156)
      JAMA Surg. 2022 Mar 01;157(3):189-198. (PMID: 34985503)
      Am J Transplant. 2007 May;7(5):1265-70. (PMID: 17359503)
      Liver Int. 2015 Jan;35(1):156-63. (PMID: 24351095)
      Liver Int. 2019 May;39(5):788-801. (PMID: 30843314)
      World J Surg. 2022 Jul;46(7):1776-1787. (PMID: 35419624)
      Transplantation. 1998 Aug 15;66(3):302-10. (PMID: 9721797)
      Front Immunol. 2022 Jul 26;13:940094. (PMID: 35958587)
      Am J Transplant. 2021 Feb;21(2):614-625. (PMID: 32713098)
      Transplant Proc. 2004 Nov;36(9):2796-8. (PMID: 15621152)
      Cell. 2001 Oct 5;107(1):43-54. (PMID: 11595184)
      Hepatology. 1998 Aug;28(2):281-5. (PMID: 9695988)
      Assay Drug Dev Technol. 2007 Jun;5(3):391-401. (PMID: 17638539)
      Transplantation. 1990 Jun;49(6):1074-80. (PMID: 2163132)
      Am J Transplant. 2016 Mar;16(3):850-9. (PMID: 26663518)
      Liver Transpl. 2012 Feb;18(2):166-76. (PMID: 22006860)
      Br J Surg. 2010 Oct;97(10):1461-75. (PMID: 20645395)
      Anesthesiology. 2014 Dec;121(6):1217-25. (PMID: 25225820)
      World J Hepatol. 2015 Mar 27;7(3):460-7. (PMID: 25848470)
      Front Med (Lausanne). 2021 Oct 06;8:753268. (PMID: 34692739)
      J Clin Anesth. 2021 Sep;72:110285. (PMID: 33838534)
      Mol Med. 2018 May 16;24(1):22. (PMID: 30134815)
      Cardiovasc Diabetol. 2014 Feb 24;13:52. (PMID: 24564828)
      Transplantation. 2019 May;103(5):938-943. (PMID: 30063694)
      Liver Transpl. 2013 Nov;19 Suppl 2:S6-8. (PMID: 24038766)
      Am J Physiol Renal Physiol. 2011 May;300(5):F1235-43. (PMID: 21270095)
      Nucleic Acids Res. 2007;35(8):e57. (PMID: 17392344)
      J Clin Anesth. 2021 Oct;73:110379. (PMID: 34087659)
      Hepatobiliary Pancreat Dis Int. 2018 Oct;17(5):387-391. (PMID: 30352672)
      J Exp Med. 2007 Nov 26;204(12):2913-23. (PMID: 17984303)
      Hepatobiliary Pancreat Dis Int. 2019 Oct;18(5):423-429. (PMID: 30853253)
      J Exp Med. 2011 Mar 14;208(3):417-20. (PMID: 21357740)
      Anesth Analg. 2019 Dec;129(6):1749-1760. (PMID: 31743197)
      Transplant Proc. 2020 Jun;52(5):1477-1480. (PMID: 32252997)
    • Grant Information:
      UL1 TR002378 United States TR NCATS NIH HHS
    • Accession Number:
      S88TT14065 (Oxygen)
    • Publication Date:
      Date Created: 20240328 Date Completed: 20240401 Latest Revision: 20240531
    • Publication Date:
      20240531
    • Accession Number:
      PMC10977716
    • Accession Number:
      10.1371/journal.pone.0301281
    • Accession Number:
      38547092