Ischemic preconditioning improves liver tolerance to congestion-reperfusion injury in mice

Background: Congestion-reperfusion injury (CRI) is a common complication after living donor liver transplantation, which has not been fully understood. It causes more severe inflammatory response as compared with ischemia-reperfusion injury (IRI). Ischemic preconditioning (IPC) has been endowed with powerful protective properties toward IRI. This study aimed to investigate whether IPC also has a protective effect against CRI and potential underlying mechanisms. Materials and methods: Mice were randomly divided into sham operation, CRI, IPC-CRI, and congestion precondition (CPC-CRI) group. The hepatic vein of the left anterior hepatic lobe was occluded for 75 min followed by reperfusion in the CRI group. The blood inflow was previously clamped for 10 min followed by 10 min of reperfusion just before occluding the hepatic vein in the IPC-CRI group. To imitating IPC in the CPC-CRI group, 10 min of congestion followed by 10 min of reperfusion just before CRI was performed. The animals were sacrificed at 2, 6, 24, 48 h, and 7 d after reperfusion. The blood and liver samples were collected for hepatic function assay, histology, terminal deoxynucleotidyl transferase dUTP nick end labeling, myeloperoxidase, and real-time polymerase chain reaction analysis. Results: Mice in the CRI, IPC-CRI, and CPC-CRI group demonstrated elevated liver enzymes, histologic damage, cellular apoptosis, and inflammatory response compared with those in the sham operation group. Compared with the CRI group, mice in the IPC-CRI group expressed lower alanine transaminase activities (2 h: 839.2 +/- 132.5 versus 384.2 +/- 94.8, P < 0.01; and 6 h: 680 +/- 142.4 versus 342.3 +/- 99.7, P < 0.01) and lower myeloperoxidase levels (2 h: 7.1 +/- 4.0 U/g versus 3.8 +/- 1.6 U/g, P < 0.05; and 6 h: 8.1 +/- 1.3 U/g versus 5.2 +/- 3.0 U/g, P < 0.05). However, the alanine transaminase level in the CPC-CRI group was notably higher at 2 h (839.2 +/- 132.5 versus 1087.5 +/- 192.5, P < 0.05). Livers from mice in the IPC-CRI group showed better tissue integrity, diminished hepatocellular injury, and apoptosis at 2 and 6 h. The messenger RNA transcriptions of interleukin 1 and interleukin 6 were significantly lower after 2-24 h of reperfusion, whereas tumor necrosis factor a and monocyte chemoattractant protein 1 were significantly lower after 24 h of reperfusion in the IPC-CRI group. Conclusions: IPC can significantly improve liver tolerance to CRI by attenuating neutrophil infiltration, proinflammatory cytokine formation, and hepatocytes apoptosis. This pretreatment strategy holds greater prospect of being translated into clinical use in living donor liver transplantation. (C) 2014 Elsevier Inc. All rights reserved.