Background. Damage to the endothelium has been established as a key pathological process in lung transplantation and ex vivo\nlung perfusion (EVLP), a new technology that provides a platform for the assessment of injured donor lungs. Damage to the lung\nendothelial glycocalyx, a structure that lines the endothelium and is integral to vascular barrier function, has been associated with\nlung dysfunction. We hypothesised that endothelial glycocalyx shedding occurs during EVLP and aimed to establish a porcine\nmodel to investigate the mechanism underlying glycocalyx breakdown during EVLP. Methods. Concentrations of endothelial\nglycocalyx breakdown products, syndecan-1, hyaluronan, heparan sulphate, and CD44, were measured using the ELISA and\nmatrix metalloproteinase (MMP) activity by zymography in the perfusate of both human (n =9) and porcine (n =4) lungs\nundergoing EVLP. Porcine lungs underwent prolonged EVLP (up to 12 hours) with perfusion and ventilation parameters\nrecorded hourly. Results. During human EVLP, endothelial glycocalyx breakdown products in the perfusate increased over time.\nIncreasing MMP-2 activity over time was positively correlated with levels of syndecan-1 (r =0.886; p =0.03) and hyaluronan\n(r =0.943; p =0.02). In the porcine EVLP model, hyaluronan was the only glycocalyx product detectable during EVLP (1 hr: 19\n(13-84) vs 12 hr: 143 (109-264) ng/ml; p =0.13). Porcine hyaluronan was associated with MMP-9 activity (r =0.83; p =0.02) and\nalso with dynamic compliance (r =0.57; p =0.03). Conclusion. Endothelial glycocalyx products accumulate during both porcine\nand human EVLP, and this accumulation parallels an accumulation of matrix-degrading enzyme activity. Preliminary evidence in\nour porcine EVLP model suggests that shedding may be related to organ function, thus warranting additional study.
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