ENDOTHELIAL GLYCOCALYX SHEDDING PREDICTS DONOR ORGAN ACCEPTABILITY AND IS ASSOCIATED WITH PRIMARY GRAFT DYSFUNCTION IN LUNG TRANSPLANT RECIPIENTS

Background The endothelial glycocalyx, a sieve-like structure located on the luminal surface of all blood vessels, has been found to be integral to regulation of capillary permeability and mechanotransduction. Given this, we investigated the role of endothelial glycocalyx breakdown products in organ donors and recipients in terms of acceptability for transplant and risk of primary graft dysfunction (PGD). Methods Endothelial glycocalyx breakdown products were measured in the peripheral blood of 135 intended and actual organ donors. Breakdown product levels were tested for association with donor demographic and clinical data, organ acceptability for transplant along with lung recipient outcomes (n=35). Liquid chromatography mass-spectrometry analysis was performed to confirm glycosaminoglycan levels and sulphation patterns on donor samples (n=15). In transplant recipients (n=50), levels were measured pre-transplant and daily for 4 days post-transplant. Levels were correlated with PGD severity and intubation time. Results Decreased hyaluronan levels in peripheral blood independently predicted organ acceptability in intended and actual donors (OR 0.96; (95%CI: 0.93-0.99) p=0.026). Furthermore, high donor syndecan-1 levels were associated with PGD in recipients (3142(1575-4829) vs 6229(4009-8093)pg/ml; p=0.045). In recipient blood, levels of syndecan-1 were correlated with severe (Grade 2-3) PGD at 72 hrs post-transplant (5982((3016-17191) vs 3060(2005-4824))pg/ml; p=0.01). Conclusions Endothelial glycocalyx breakdown occurs in lung transplant donors and recipients and predicts organ acceptability and development of PGD. Glycocalyx breakdown products may be useful biomarkers in transplantation, and interventions to protect the glycocalyx could improve transplant outcomes. Corresponding Author/ Reprint requests: Daniel Chambers, MBBS, MD, Queensland Lung Transplant Service, Level 1, Administration Building, The Prince Charles Hospital, Rode Rd, Chermside, Queensland, 4032, Australia. Telephone: +61-7-31394000. Fax +61-7-31395696. E-mail address: daniel.chambers@health.qld.gov.au Authors contributions: Timothy M Sladden contributed to research design, performance of the research, data analysis and writing of the paper. Stephanie Yerkovich and Daniel C Chambers contributed equally to research design, data analysis and writing of the paper. Michelle Grant, Michael Trotter and Peter Hopkins contributed to data collection and/ or analysis and critical revision of the manuscript. Xinyue Liu and Fuming Zhang contributed to performance of research, data analysis and writing of the paper. Robert J Linhardt contributed to analytic tools, data analysis and writing of the paper. Disclosures: The authors declare no conflicts of interest. Funding: This research was funded by a Program Grant from the Prince Charles Hospital Foundation and National Health and Medical Research Council Project Grant # 1103862. Neither funding source were involved in the research or manuscript preparation. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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