Impact of Heparin on Endothelial Glycocalyx in Lung Grafts during Ex Vivo Lung Perfusion

Abstract

Purpose Endothelial glycocalyx degradation is known to critically affect graft quality. Glycocalyx protection and preservation during ex vivo lung perfusion (EVLP) may increase conversion to transplant and improve posttransplant outcomes. To date it is unclear the role of routine heparin use on graft protection during current EVLP regardless of blood product use in perfusate. Heparin may protect glycocalyx via inhibiting heparanase activity. In this study, we investigated the effect of heparin on intragraft endothelial protection and graft quality during EVLP. Methods Using a rat EVLP model, 1000U heparin/100mL Steen solution was administered into the perfusate every hour for 4 hours and lung physiologic parameters were monitored. After 4 hours, the perfusate and tissue samples were analyzed for endothelial glycocalyx integrity. Data were compared between lungs with/without heparin treatment. Results Compared to control tissues, heparin significantly decreased heparanase activity and matrix metalloprotease-9 expression in lung tissue during EVLP. (Figure 1A) We also detected increased levels of syndecan-1 in perfusate during 4h EVLP with heparin. (Figure 1B) Additionally, no significant differences were observed between heparin-treated and control lung tissues regarding gene expression of proinflammatory cytokines, physiological parameters, tissue glycosaminoglycans, and edema development. Conclusion This study suggests that heparin inhibits heparanase activity in lung tissue during EVLP; however, it may enhance endothelial glycocalyx breakdown. As a result, our findings raise concerns about the use of heparin during EVLP. Alternative treatments aimed at protecting and maintaining graft endothelial cell viability/health during EVLP may result in improved graft preservation and outcomes.