Comparable Levels of Inflammatory Mediators in Portal Venous Blood Collected from Organ Donors Donating after Circulatory Death and those Donating after Brain Death
Janske Reiling1,2,3,4, Daniel M Hohenhaus5, Matt J Sweet5, Ashok S Raj1,6, Catherine M Campbell7, Kim R Bridle1,2, Nishreen Santrampurwala1,2, Laurence J Britton1,2,6, Darrell HG Crawford1,2, Cornelis HC Dejong4,8, Jonathan Fawcett1,2,3,9.
1Faculty of Medicine, The University of Queensland, Brisbane, Australia; 2Gallipoli Medical Research Institute, Greenslopes Private Hospital, Brisbane, Australia; 3Princess Alexandra Research Foundation, Princess Alexandra Hospital, Brisbane, Australia; 4Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, , Maastricht, Netherlands; 5Institute for Molecular Bioscience (IMB), and IMB centre for Inflammation and Disease Research, , University of Queensland, Brisbane, Australia; 6Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Australia; 7Envoi Specialist Pathologists, Brisbane, Australia; 8Department of Surgery, RWTH Universitätsklinikum Aachen, Aachen, Germany; 9Queensland Liver Transplant Service, Princess Alexandra Hospital, Brisbane, Australia
Introduction: Extended criteria donors, such as those who donate after cardiac death (DCD) are increasingly considered for transplantation. Biliary stricture formation often complicates the use of these grafts and the aetiology remains largely unknown. We have previously shown that endotoxins, in the form of lipopolysaccharides (LPS), are potent inducers of biliary injury. However, it remains unclear if endotoxaemia occurs during DCD organ donation. The aim of this study was to determine the inflammatory propensity of portal blood collected from DCD donors compared to those donating after brain death (DBD).
Materials and Methods: Serial portal venous as well as hepatic venous blood samples were collected from adult DBD and DCD organ donors. An NF-κB-dependent cell-based assay was used to detect endotoxins and/or other inflammatory stimuli in the portal blood samples. β-galactosidase activity in hepatic venous samples was assessed as a marker for hepatic Kupffer cell activation. In addition, bile and bile duct tissue was collection for assessment of biliary injury.
Results and Discussion: Thirty patients (nine DCD, 21 DBD) were included in this study. Compared to DBD donors, portal samples of DCD donors did not have an enhanced propensity for triggering inflammatory responses. However, Kupffer cell activation was enhanced and prolonged in DCD donors. Lactate dehydrogenase as a biomarker of biliary injury was increased in bile collected from DCD donors and histological scoring showed evidence of increased injury of peri-luminal peribiliary glands.
Conclusion: In this study no evidence was found of endotoxaemia or increased propensity to produce an inflammatory response in portal blood collected from DCD donors. Despite this, hepatic Kupffer cell activation was increased and there was evidence of biliary injury.
Liver Transplant Bequest, PA Research Foundation, Princess Alexandra Hospital, Brisbane, Australia. . Gallipoli Medical Research Foundation, Greenslopes Private Hospital, Brisbane, Australia.
