Effect of normothermic mechanical portal vein perfusion pressure on repairing donor liver injury induced by prolonged warm ischemia in rats / 中华器官移植杂志

ABSTRACT

Objective:To develop an ex vivo normothermic mechanical perfusion(NMP)and compare the effect of different portal perfusion pressures on attenuating hepatic injury from donor after cardiac death(DCD).Methods:All rat livers were subjected to in situ warm ischemia for 30 min after cardiac attest and thereafter stored for 8 h under cold preservation. Six livers were harvested and regarded as static cold storage(group CS, n=6). In experimental group, liver received an ex vivo dual NMP with oxygenated perfusion via hepatic artery for 2 h after cold storage. Hepatic injury was assessed and compared from perfused livers with full portal vein pressure(group M1, n=6)and low portal vein pressure(group M2, n=6). The evaluation parameters included perfusion flow, liver enzymes of perfusate, pathological changes by hematoxylin-eosin staining, Suzuki histological criteria, expression of activation markers of polymorphonuclear neutrophils and macrophages, myeloperoxidase (MPO)and CD68 by immunohistochemistry, level of malondialdehyde(MDA)and activity of superoxide dismutase(SOD). Results:In experimental group during NMP, perfusion flows tended to increase when portal pressures were stabilized in groups M1 and M2.Perfusion flow during NMP 60~120 min was significantly higher than during NMP 0~20 min.After NMP with full portal pressure, hepatic sinusoidal congestion, hepatocyte necrosis, steatosis and Suzuki criteria were lower in group M1 than those in group CS( P<0.05). Compared with group M1, lower hepatic injury was characterized with a lower change of liver enzymes in perfusate( P<0.05), a better histological evaluation( P<0.05), a lower level of MDA and a higher activity of SOD( P<0.05), lower expressions of CD68 and MPO ( P<0.05)and lower levels of TNF-α and IL-6( P<0.05)in perfused liver. Conclusions:The ex vivo dual NMP with oxygenated perfusion via hepatic artery mimics liver perfusion under the physiological conditions.NMP with a lower portal pressure can attenuate hepatic ischemia-reperfusion injury and confer a better protection against liver damage from DCD.