Endothelial glycocalyx damage marker Syndecan-1 measured during hypothermic oxygenated machine perfusion predicts early allograft dysfunction after liver transplantation
Laurin Rauter1, Dagmar Kollmann2, Judith Schiefer3, Marija Spasic1, Pierre Raeven3, Jule Dingfelder1,2, David Pereyra1,2, David Baron3, Effimia Pompouridou1, Thomas Soliman1, Gabriela Berlakovich1, Georg Györi1.
1Department of General Surgery, Division of Transplantation, Medical University of Vienna, Vienna, Austria; 2Department of General Surgery, Division of Visceral Surgery, Medical University of Vienna, Vienna, Austria; 3Department of Anesthesia, Intensive Care Medicine and Pain Medicine, Medical University of Vienna, Vienna, Austria
Background: During liver transplantation, the graft has to endure a damaging ischemic phase and additional injury after reperfusion (IRI), particularly mediated by reactive oxygen species (ROS). The endothelial glycocalyx covers the luminal side of the vascular endothelium and regulates vascular permeability, modulates adhesion of leucocytes onto the vascular wall and transduces mechanical shear stress. It is very sensitive to ROS and therefore degraded during graft preservation and reperfusion. Hypothermic oxygenated machine perfusion (HOPE) is a preservation strategy that can reduce IRI-inflicted graft injury compared to static cold storage (SCS). We aimed to measure glycocalyx degradation after HOPE or SCS alone, to evaluate its viability-assessment potential for liver transplantation.
Methods: We measured glycocalyx degradation via ELISA for its main component Syndecan-1, in samples from 77 liver transplant patients. 37 grafts were directly transplanted after SCS, 40 grafts additionally underwent HOPE with the Organ Assist® perfusion system, prior to liver transplantation.
Results: Compared to SCS alone [4011 (3382-4683)], Sdc-1 concentrations in the graft effluent are significantly lower after HOPE [466 (350-1073) , p<0.001]. Further, Sdc-1 concentrations regenerate faster towards baseline levels on postoperative day 1 [HOPE: 362 (232-880) vs. SCS: 1017 (637-1900), p<0.001], indicating a shorter postoperative glycocalyx shedding period. Regarding viability assessment, Sdc-1 concentrations in the perfusate were elevated after 60 minutes of HOPE in patients who later developed EAD, compared to non-EAD patients [896 (419-1681) vs. 429 (260-556), p=0.018]. Additionally ROC-analysis indicated a significant discriminatory value of Sdc-1 concentration after 60 minutes of HOPE regarding the occurrence of EAD with an AUC of 74.0% (p=0.018, sensitivity 66.7% and specificity 84.6%).
Conclusions: HOPE reduces the postoperative duration of glycocalyx shedding, evident by Sdc-1 release in recipient serum after liver transplantation. Sdc-1 concentration during HOPE can predict early allograft dysfunction. Therefore, Sdc-1 could be a potential viability assessment marker in liver transplantation.