Bile as parameter for quality assessment during normothermic ex vivo rat liver machine perfusion

Introduction Organ shortage for liver transplantation is a worldwide problem, necessitating the use of extended criteria donor (ECD) organs. Normothermic ex vivo liver machine perfusion (NEVLP) can be used to assess and resuscitate ECD grafts. Our aim was to evaluate bile as a parameter for quality assessment of ECD grafts in our rodent model of rat NEVLP.

Methods Liver grafts from 24 male Sprague Dawley rats were divided into four groups and underwent 6 hours of NEVLP: 45min of warm ischemia (ECD model) using either DMEM or Steen®​ solution as perfusate, and healthy livers without prolonged ischemia using DMEM or Steen®​ as controls. Bile was collected and biliary pH was assessed hourly. AST, ALT, LDH and Urea levels were measured in perfusate samples every three hours. HE- and TUNEL-staining were performed at the end of perfusion.

Results A significant increase in liver enzymes was seen in livers exposed to prolonged warm ischemia compared to healthy livers (ALT T6h: 201.6U/L vs. 821.2U/L; p=0.004), along with organ damage in HE-staining. Bile secretion of ECD grafts was significantly decreased compared to healthy livers (e. g. T1h-2h: 1223mg vs 282mg; p < 0.0001), while bile pH was significantly increased in both ECD groups (e. g. T1h-2h: pH 7.965 vs. 8.645; p < 0.0001). Differences between DMEM and Steen perfusate were not found.

Conclusion Bile secretion and pH can be used as parameter of liver integrity in our rat NEVLP model. We propose to perform bile analyses to assess the quality of marginal grafts during clinical NEVLP.

Publikationsverlauf

Artikel online veröffentlicht:
26. Januar 2022