Sanguineous normothermic machine perfusion improves hemodynamics and biliary epithelial regeneration in DCD porcine livers

摘要

The effect of normothermic machine perfusion (NMP) on post-reperfusion hemodynamics and extrahepatic biliary duct histology of donors after cardiac death (DCD) livers after transplantation has not been addressed thoroughly and represented the object of this study. Ten livers (n=5/group) with 60’ of warm ischemia were preserved by cold storage (CS) or sanguineous NMP for 10 hours, and then reperfused for 24 hours with whole blood in an isolated perfusion system to simulate transplantation. In our experiment, arterial and portal venous flows were stable in NMP group during the entire simulated reperfusion, while decreased dramatically in CS group after 16 hours post-reperfusion (P<.05), findings consistent with severe parenchymal injury. Similarly, significant differences existed between CS and NMP group on hepatocellular enzyme release, bile volume produced, and enzyme released into bile (P<.05). On histology CS livers presented with diffuse hepatocyte congestion, necrosis, intraparenchymal hemorrhage, denudated biliary epithelium and submucosal bile duct necrosis, while NMP liver showed very mild injury in liver parenchyma and biliary architecture. Most importantly, Ki67 staining in extrahepatic bile duct showed biliary epithelial regeneration. Our findings advance the knowledge of post-reperfusion events that characterize DCD livers and propose NMP as a beneficial preservation modality able to improve biliary regeneration after a major ischemic event, which may prevent in clinical transplantation the development of ischemic cholangiopathy.