THORACIC – Original Submission|Articles in Press

Effects of Intraoperative Support Strategies on Endothelial Injury and Clinical Lung Transplant Outcomes

Published:January 27, 2023DOI:
      In lung transplantation, postoperative outcomes favor intraoperative use of extracorporeal membrane oxygenation (ECMO) over cardiopulmonary bypass (CBP). We investigated the effect of intraoperative support strategies on endothelial injury biomarkers and short-term posttransplant outcomes. Adults undergoing bilateral lung transplantation with No-Support, venoarterial (V-A) ECMO, or CPB were included. Plasma samples pre- and post-transplant were collected for Luminex assay to measure endothelial injury biomarkers including syndecan-1 (SYN-1), intercellular adhesion molecule-1 (ICAM-1), and matrix metalloprotease-9. Fifty five patients were included for analysis. The plasma level of SYN-1 at arrival in the intensive care unit was significantly higher with CPB compared to V-A ECMO and No-Support (P < 0.01). The rate of primary graft dysfunction grade 3 (PGD3) at 72 hours was 60.0% in CPB, 40.1% in V-A ECMO, and 15% in No-Support (P = 0.01). Postoperative plasma levels of SYN-1 and ICAM-1 were significantly higher in recipients who developed PGD3 at 72 hours. SYN-1 levels were also significantly higher in patients who developed acute kidney injury and hepatic dysfunction after transplant. Postoperative, SYN-1 upon intensive care arrival was found to be a significant predictive biomarker of PGD3, acute kidney injury, and hepatic dysfunction following lung transplantation. CPB is associated with higher plasma concentrations of SYN-1, a marker of endothelial glycocalyx degradation, upon arrival to the intensive care unit. Higher levels of SYN-1 are predictive of end-organ dysfunction following lung transplantation. Our data suggests that intraoperative strategies aimed at modulating endothelial injury will help improve lung transplantation outcomes.

      Graphical abstract



      AKI (acute kidney injury), BMI (body mass index), CIT (cold ischemic time), CPB (cardiopulmonary bypass), ECLS (extracorporeal life support), ECMO (extracorporeal membrane oxygenation), ICAM-1 (intercellular adhesion molecule 1), ICU (intensive care unit), MMP (matrix metalloprotease), MV (mechanical ventilation), PGD (primary graft dysfunction), RBC (red blood cells), RRT (renal replacement therapy), SYN-1 (syndecan-1), UNOS (United Network for Organ Sharing), V-A ECMO (veno-arterial extracorporeal membrane oxygenation)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Seminars in Thoracic and Cardiovascular Surgery
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Van Raemdonck D
        • Hartwig MG
        • Hertz MI
        • et al.
        Report of the ISHLT Working Group on primary lung graft dysfunction Part IV: Prevention and treatment: A 2016 Consensus Group statement of the International Society for Heart and Lung Transplantation.
        J Heart Lung Transplant. 2017; 36: 1121-1136
        • Coster JN
        • Loor G
        Extracorporeal life support during lung transplantation.
        Indian J Thorac Cardiovasc Surg. 2021; 37: 476-483
        • American Association for Thoracic Surgery: Digital Education & Resource Center
        Presentation: “AATS Expert Consensus: The use of mechanical circulatory support in lung transplantation.” May 16, Boston, MA2022 (Presenter: M. Hartwig; 102nd Annual MeetingAvailable at) (Accessed August 6, 2022)
        • Biscotti M
        • Yang J
        • Sonett J
        • et al.
        Comparison of extracorporeal membrane oxygenation versus cardiopulmonary bypass for lung transplantation.
        J Thorac Cardiovasc Surg. 2014; 148: 2410-2415
        • Ius F
        • Kuehn C
        • Tudorache I
        • et al.
        Lung transplantation on cardiopulmonary support: Venoarterial extracorporeal membrane oxygenation outperformed cardiopulmonary bypass.
        J Thorac Cardiovasc Surg. 2012; 144: 1510-1516
        • Machuca TN
        • Collaud S
        • Mercier O
        • et al.
        Outcomes of intraoperative extracorporeal membrane oxygenation versus cardiopulmonary bypass for lung transplantation.
        J Thorac Cardiovasc Surg. 2015; 149: 1152-1157
        • Magouliotis DE
        • Tasiopoulou VS
        • Svokos AA
        • et al.
        Extracorporeal membrane oxygenation versus cardiopulmonary bypass during lung transplantation: A meta-analysis.
        Gen Thorac Cardiovasc Surg. 2018; 66: 38-47
        • Hoechter DJ
        • Shen YM
        • Kammerer T
        • et al.
        Extracorporeal circulation during lung transplantation procedures: A meta-analysis.
        ASAIO J. 2017; 63: 551-561
        • Uchimido R
        • Schmidt EP
        • Shapiro NI
        The glycocalyx: A novel diagnostic and therapeutic target in sepsis.
        Critical Care. 2019; 23
        • Zhang D
        • Li L
        • Chen Y
        • et al.
        Syndecan-1, an indicator of endothelial glycocalyx degradation, predicts outcomes of patients admitted to an ICU with COVID-19.
        Mol Med. 2021; 27
        • Brettner F
        • von Dossow V
        • Chappell D
        The endothelial glycocalyx and perioperative lung injury.
        Curr Opin Anesthesiol. 2017; 30: 36-41
        • Rancan L
        • Simon C
        • Pedrosa GS
        • et al.
        Glycocalyx degradation after pulmonary transplantation surgery.
        Eur Surg Res. 2018; 59: 115-125
        • Shah RJ
        • Bellamy SL
        • Localio AR
        • et al.
        A panel of lung injury biomarkers enhances the definition of primary graft dysfunction (PGD) after lung transplantation.
        J Heart Lung Transplant. 2012; 31: 942-949
        • Yano Y
        • Omoto Y
        • Yamakawa Y
        • et al.
        Increased matrix metalloproteinase 9 activity and mRNA expression in lung ischemia-reperfusion injury.
        J Heart Lung Transplant. 2001; 20: 679-686
        • Allen JG
        • Lee MT
        • Weiss ES
        • et al.
        Preoperative recipient cytokine levels are associated with early lung allograft dysfunction.
        Ann Thorac Surg. 2012; 93: 1843-1849
        • Sladden TM
        • Yerkovich S
        • Grant M
        • et al.
        Endothelial glycocalyx shedding predicts donor organ acceptability and is associated with primary graft dysfunction in lung transplant recipients.
        Transplantation. 2019; 103: 1277-1285
        • Dekker NAM
        • Veerhoek D
        • Koning NJ
        • et al.
        Postoperative microcirculatory perfusion and endothelial glycocalyx shedding following cardiac surgery with cardiopulmonary bypass.
        Anaesthesia. 2019; 74: 609-618
        • Galea J
        • Rebuck N
        • Finn A
        • et al.
        Expression of soluble endothelial adhesion molecules in clinical cardiopulmonary bypass.
        Perfusion. 1998; 13: 314-321
        • Grünenfelder J
        • Zünd G
        • Schoeberlein A
        • et al.
        Expression of adhesion molecules and cytokines after coronary artery bypass grafting during normothermic and hypothermic cardiac arrest.
        Eur J Cardiothorac Surg. 2000; 17: 723-728
        • Görlach G
        • Sroka J
        • Heidt M
        • et al.
        Intracellular adhesion molecule-1 in patients developing pulmonary insufficiency after cardiopulmonary bypass.
        Thorac Cardiov Surg. 2003; 51: 138-141
        • Schmid F
        • Floerchinger B
        • Vudattu NK
        • et al.
        Direct evidence of endothelial injury during cardiopulmonary bypass by demonstration of circulating endothelial cells.
        Perfusion. 2006; 21: 133-137
        • Covarrubias M
        • Ware LB
        • Kawut SM
        • et al.
        Plasma intercellular adhesion molecule-1 and von Willebrand factor in primary graft dysfunction after lung transplantation.
        Am J Transpl. 2007; 7: 2573-2578
        • Mathis A
        • Putzer G
        • Schneeberger S
        • Martini J
        The endothelial glycocalyx and organ preservation – from physiology to possible clinical implications for solid organ transplantation.
        Int J Mol Sci. 2022; 22
        • Atkinson JJ
        • Senior RM
        Matrix metalloproteinase-9 in lung remodeling.
        Am J Respir Cell Mol Biol. 2003; 28: 12-24
        • VanTeeffelen JWGE
        • Brands J
        • et al.
        Heparin impairs glycocalyx barrier properties and attenuates shear dependent vasodilation in mice.
        Hypertension. 2007; 50: 261-267
        • Nguyen KT
        • Donoghue L
        • Giridharan GA
        • et al.
        Acute response of human aortic endothelial cells to loss of pulsatility during as seen during cardiopulmonary bypass.
        Cells Tissues Organs. 2022; 211: 324-334
      1. Zhang, Y, Zeng, J, Li, J, et al.. Pulsatility protects endothelial function during extracorporeal membrane oxygenation. Res Square.