Queensland Lung Transplant Service, The Prince Charles Hospital, Brisbane, Australia.
Faculty of Medicine, The University of Queensland, Brisbane, Australia.
Transplantation. 2019 Jun;103(6):1277-1285. doi: 10.1097/TP.0000000000002539.
The endothelial glycocalyx, a sieve-like structure located on the luminal surface of all blood vessels, has been found to be integral to regulation of capillary permeability and mechanotransduction. Given this, we investigated the role of endothelial glycocalyx breakdown products in organ donors and recipients in terms of acceptability for transplant and risk of primary graft dysfunction (PGD).
Endothelial glycocalyx breakdown products were measured in the peripheral blood of 135 intended and actual organ donors. Breakdown product levels were tested for association with donor demographic and clinical data, organ acceptability for transplant along with lung recipient outcomes (n = 35). Liquid chromatography mass spectrometry analysis was performed to confirm glycosaminoglycan levels and sulfation patterns on donor samples (n = 15). In transplant recipients (n = 50), levels were measured pretransplant and daily for 4 days posttransplant. Levels were correlated with PGD severity and intubation time.
Decreased hyaluronan levels in peripheral blood independently predicted organ acceptability in intended and actual donors (odds ratio, 0.96; [95% confidence interval, 0.93-0.99] P = 0.026). Furthermore, high donor syndecan-1 levels were associated with PGD in recipients (3142 [1575-4829] versus 6229 [4009-8093] pg/mL; P = 0.045). In recipient blood, levels of syndecan-1 were correlated with severe (grades 2-3) PGD at 72 hours posttransplant (5982 [3016-17191] versus 3060 [2005-4824] pg/mL; P = 0.01).
Endothelial glycocalyx breakdown occurs in lung transplant donors and recipients and predicts organ acceptability and development of PGD. Glycocalyx breakdown products may be useful biomarkers in transplantation, and interventions to protect the glycocalyx could improve transplant outcomes.
内皮糖萼位于所有血管的腔面,是一种筛状结构,已被发现对毛细血管通透性和机械转导的调节至关重要。鉴于此,我们研究了内皮糖萼降解产物在器官供体和受体中的作用,以评估其对移植的可接受性和原发性移植物功能障碍(PGD)的风险。
测量了 135 名拟议和实际器官供体的外周血中的内皮糖萼降解产物。测试了分解产物水平与供体人口统计学和临床数据、器官移植接受能力以及肺受体结局之间的相关性(n=35)。对供体样本进行了液相色谱-质谱分析,以确认糖胺聚糖水平和硫酸化模式(n=15)。在移植受者(n=50)中,在移植前和移植后 4 天每天测量水平。将水平与 PGD 严重程度和插管时间相关联。
外周血中透明质酸水平降低独立预测了拟议和实际供体的器官可接受性(优势比,0.96;[95%置信区间,0.93-0.99] P=0.026)。此外,供体高硫酸乙酰肝素 1 水平与受体的 PGD 相关(3142[1575-4829]与 6229[4009-8093]pg/ml;P=0.045)。在受体血液中,硫酸乙酰肝素 1 水平与移植后 72 小时严重(2-3 级)PGD 相关(5982[3016-17191]与 3060[2005-4824]pg/ml;P=0.01)。
肺移植供体和受体中发生内皮糖萼降解,并预测器官可接受性和 PGD 的发生。糖萼降解产物可能是移植中的有用生物标志物,保护糖萼的干预措施可能改善移植结果。