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

Syndecan-1 levels increased during normothermic machine perfusion in liver grafts.

• Thirty grafts undergoing NMP prior to transplantation were analyzed in this prospective pilot study.
• Syndecan-1 was quantified in perfusate samples collected during NMP.
• Levels rose over the course of the NMP period, indicating ongoing glycocalyx shedding during machine perfusion.
• The study was registered at ClinicalTrials.gov with identifier NCT: 04764266.

Syndecan-1 levels were significantly elevated in grafts from donation after circulatory death (DCD) donors compared with donation after brain death (DBD) donors during NMP.

• DCD and DBD donors were compared within the cohort of 30 NMP-perfused grafts.
• Syndecan-1 remained significantly elevated in DCD grafts throughout the NMP period.
• This finding suggests greater endothelial vulnerability in DCD livers, likely reflecting greater baseline ischemic injury prior to NMP.
• Donor-related factors influencing glycocalyx injury during NMP were specifically assessed.

A syndecan-1 cut-off of 4,796.13 ng/mL after 6 hours of NMP showed predictive potential for early allograft dysfunction (EAD).

• Receiver operating characteristics (ROC) analysis was used to assess predictive potential for EAD.
• The identified cut-off value was 4,796.13 ng/mL of syndecan-1 in the perfusate at the 6-hour NMP time point.
• Correlations between glycocalyx markers and postoperative outcomes were established.
• This suggests syndecan-1 during NMP may serve as a biomarker for graft quality assessment prior to implantation.

Heparan sulfate concentrations showed no relevant changes during NMP or postoperatively.

• Heparan sulfate was quantified alongside syndecan-1 in both perfusate and recipient serum.
• In contrast to syndecan-1, heparan sulfate showed no relevant changes during NMP.
• Postoperatively, heparan sulfate remained stable in recipient serum.
• The divergent behavior of the two glycocalyx components suggests differential shedding mechanisms or sensitivities to IRI.

Postoperative recipient serum syndecan-1 levels were elevated immediately after transplantation but declined over subsequent days.

• Syndecan-1 was measured in recipient serum at multiple postoperative time points.
• Levels were elevated immediately after transplantation, consistent with reperfusion-associated glycocalyx injury.
• Syndecan-1 concentrations declined over subsequent postoperative days, suggesting partial recovery of endothelial integrity.
• Heparan sulfate remained stable in recipient serum throughout the postoperative period.

Glycocalyx degradation via syndecan-1 shedding represents a potentially modifiable aspect of graft physiology relevant to future protective strategies.

• The authors interpret elevated syndecan-1 during NMP as reflecting endothelial vulnerability.
• They suggest that glycocalyx injury during NMP is particularly pronounced in DCD livers.
• The findings point toward NMP as a platform for implementing glycocalyx-protective interventions prior to transplantation.
• Ischemia-reperfusion injury was identified as the pivotal mechanism driving glycocalyx degradation, oxidative stress, and microcirculatory dysfunction.