Effect of Normothermic Machine Perfusion on Glycocalyx Shedding During Liver Transplantation – A Prospective Pilot Study

Ischemia-reperfusion injury (IRI) plays a pivotal role in liver transplantation by inducing oxidative stress and inflammation, thereby contributing to impaired graft function and postoperative complications. A key element of IRI is degradation of the endothelial glycocalyx, resulting in microcirculatory dysfunction. This study investigated the impact of normothermic machine perfusion (NMP) on glycocalyx integrity and its association with early postoperative outcomes. Thirty grafts undergoing NMP prior to transplantation were analyzed. Syndecan-1 and heparan sulfate were quantified in perfusate and recipient serum. Donor-related factors influencing glycocalyx injury during NMP were assessed, and correlations with outcomes established. Syndecan-1 levels increased during NMP and remained significantly elevated in grafts from circulatory-death (DCD) donors compared with brain-death (DBD) donors. Receiver operating characteristics revealed predictive potential for early allograft dysfunction (EAD) with a syndecan-1 cut-off of 4,796.13 ng/mL after 6 h of NMP. In contrast, heparan sulfate concentrations showed no relevant changes. Postoperatively, syndecan-1 levels in recipient serum were elevated immediately after transplantation but declined over subsequent days, while heparan sulfate remained stable. These findings indicate that glycocalyx injury develops during NMP, particularly in DCD livers, with elevated syndecan-1 reflecting endothelial vulnerability and a potentially modifiable aspect of graft physiology relevant to future protective strategies. Clinical Trial Registration: www.Clinicaltrials.gov, identifier NCT: 04764266.