Glycocalyx as a Useful Marker of Endothelial Injury in Liver Transplantation: The Role of Preservation Solution.

Abstract

The reported investigations from Schiefer et al,1 on the role of glycocalyx (GC) in orthotopic liver transplantation, propose GC as a relevant injury marker to be used in this field. GC is a complex sugar monolayer, which covers the endothelium and is thus exposed and susceptible to alteration as a consequence of liver ischemia-reperfusion (IR) injury associated with orthotopic liver transplantation. The authors have used histidine-tryptophan-ketoglutarate (HTK) solution in their study. However, other preservation solutions (PSs) with different compositions (such as University of Wisconsin [UW], Celsior, and IGL-1 PS) are commercially available and should be tested. Extension of the study with use of these alternative PS could provide important insights into organ PS. The presence of an oncotic agent (such as hydroxyethyl starch in the UW solution or polyethylene glycol 35 [PEG35] in IGL-1 solution) differentiates UW and IGL-1 from HTK and Celsior solutions, which do not contain oncotic agents. This difference is relevant because oncotic pressure, controlled by the oncotic agent, minimizes interstitial edema, which could directly affect GC. However, the oncotic agent increases viscosity, which may in turn affect the protective performance of the PS. Balancing the limitation of edema against viscosity during organ preservation is critical to GC integrity and graft status. In this context, our group reported that PEG35 used in a rinsing solution reduces liver graft damage after cold static preservation.2 The comparison of 2 PS, HTK, and IGL-1, in a rat liver cold preservation model, showed that the presence of PEG35 in the IGL-1 PS was the determinant of GC protection.3 These data support the concept that PEG35 reduces IR injury effects on the narrowing and the integrity of the GC. GC protection is linked to the mechanical properties that PEG35 confers on PS because of its viscosity, such as shear stress and PEG35 interacting with the cells causing remodeling of the cell’s actin cytoskeleton.4 It is acknowledged that IR injury is maximized in fatty livers partly because of sinusoidal narrowing and is accentuated by both normothermic and hypothermic machine perfusion.5 In addition, nitric oxide, a potent physiological vasodilator, is promoted by PEG35 through endothelial nitric oxide synthase activation.2,3 Therefore, PEG35 should be considered as an important component in any dynamic preservation strategy, such as hypothermic oxygenated perfusion, to preserve GC integrity and improve liver preservation, especially when fatty liver grafts are used.5 Thus, we support the relevance of the investigations reported by Schieffer et al, which point firmly, for the first time, to the utility of GC as a suitable marker of graft damage and preservation in orthotopic liver transplantation. Further investigation will be important to compare GC as an injury marker using different PS.