A new designed machine perfusion system to mimic the cardiac cycle's heart function for a better hepatic microcirculation perfusion
Fan Lin1, Fu Zhen1, Ye Qi Fa1,2.
1Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Wuhan, Hubei, People's Republic of China; 2The 3rd Xiangya Hospital of Central South University, Research Center of National Health Ministry on Transplantation Medicine Engineering and Technology, Changsha,Hunan, People's Republic of China
Background: Machine perfusion is a relatively new concept developed for protecting marginal liver transplantation. However, so far, limited studies have reported on liver transplantation donated after cardiac death (DCD).
Objective: To establish and verify a novel machine perfusion concept to eliminate these risk factors and recover DCD livers.
Methods: To explore a novel hypothermic oxygenated perfusion (HOPE) system, two pumps and an elastic water sac were integrated into the perfusion system to mimic the cardiac cycle's heart function. Compared to the other two traditional systems (HOPE S1 and S2), the novel HOPE system (HOPE S3) was verified in rats by no injured livers (perfused with methylene blue diluted by UW-G) or DCD livers subjected to 60 min in situ warm ischemia, without application of heparin. Liver perfusion outcomes were compared using macroscopy, microscopy, molecular tests, and orthotopic liver transplantation (OLT).
Results: DCD livers, subjected to HOPE systems' perfusion, disclosed reduced injury and improved survival compared to static cold storage after warm ischemia of 60 min (DCD+SCS). The post-transplantation survival rates of 4 weeks were 0%, 20 and 30% in DCD+SCS, DCD+SCS+HOPE S1, and DCD+SCS+HOPE S2 group, respectively. In contrast, HOPE S3 protected from hepatocyte and non-parenchymal cell injury and led to 60% (6/10) animal survival after 60 min of warm donor ischemia (DCD+SCS+HOPE S3). These data were further demonstrated by monitoring the hepatic sinusoid microcirculation, function morphological, and molecular changes of preserved livers.
Conclusion: The newly designed novel machine perfusion system achieved complete and homogeneous liver perfusion and is regarded as a useful tool for resuscitating DCD liver grafts with severe warm ischemic injuries. Key words：Liver transplantation; Hypothermic oxyenated perfusion; Donation after cardiac death; Organ recovery; Perservayion manner; Ischemic reperfusion injury; Static cold storage; Hepatic sinusoidal; Hepatic microcirculation; Inferior vena cava.
National Natural Science Foundation of China (Grant No. 81970548). Medical Science Advancement Program (Youth Scholars) of Wuhan University (Grant No. TFZZ2018035). Science and Technology Innovation Cultivation Fund of Zhongnan Hospital of Wuhan University(No.znpy2019041).
right-click to download