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Ex Situ Normothermic Machine Perfusion of Donor Livers
Published on: May 26, 2015
A Novel Machine Perfusion System for Enhancing Hepatic Microcirculation Perfusion
Lin Fan1, Haoyang Xia1, Guizhu Peng1
1Hubei Provincial Clinical Research Center for Natural Polymer Biological Liver, Hubei Key Laboratory of Medical Technology on Transplantation, National Quality Control Center for Donated Organ Procurement, Transplant Center of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
Background:
Machine perfusion is a promising strategy for safeguarding liver transplants donated after cardiac death (DCD). In this study, we developed and validated a novel machine perfusion approach for mitigating risk factors and salvaging severe DCD livers.
Methods:
A novel hypothermic oxygenated perfusion (HOPE) system was developed, incorporating two pumps and an elastic water sac to emulate the functionality of the cardiac cycle. Compared to conventional systems (HOPE S1 and S2), the novel HOPE system (HOPE S3) was evaluated in rats, utilizing healthy livers perfused with methylene blue diluted using Histidine-tryptophan-ketoglutarate (HTK) solution or DCD livers subjected to 60 min of warm ischemia without heparin administration. Liver perfusion outcomes were assessed through macroscopic and microscopic evaluations, molecular analyses, and orthotopic liver transplantation (OLT).
Results:
DCD livers subjected to HOPE systems' perfusion exhibited decreased injury and enhanced survival rates compared to static cold storage following 60 min of warm ischemia (DCD + SCS). The 4-week post-transplantation survival rates were 0%, 20%, and 33% in the DCD + SCS, HOPE S1, and HOPE S2 groups, respectively. HOPE S3 conferred protection against hepatocyte and non-parenchymal cell injury, resulting in a 67% animal survival rate following 60 min of warm donor ischemia (HOPE S3). Assessments of hepatic sinusoidal microcirculation, morphological changes, and molecular alterations in preserved livers further confirmed these findings.
Conclusions:
The newly devised machine perfusion system can enhance and uniform liver perfusion and may become a promising tool for revitalizing DCD liver grafts afflicted with severe warm ischemic injuries.

