Cold preservation of pig liver grafts with warm ischemia and pentoxifylline-UW solution

We undertook this study to investigate the safe time limits of cold preservation in UW solution of liver grafts subjected to warm ischemia (WI) for 20 min and the changes of the limits when pentoxifylline is added to UW solution.

The safe time limit was studied in a simple porcine orthotopic liver transplantation (LTx) model. In donors, livers were subjected to 20 min of WI and subsequent 12-h (group 1, n = 5), 16-h (group 2, n = 5), and 20-h (group 3, n = 3) cold preservation in UW solution, respectively. After the safe time limits were clear, another group (group 4, n = 5) was built to test whether or not the limits can be changed when pentoxifylline is added to UW solution in an unsafe time limit group.

All five animals in group 1 survived up to 7 days of the survey endpoint. In group 2, only one animal survived up to the same survey endpoint and all animals in group 3 died within 12 h. The 1-week survival rate of group 1 was significantly higher than the other two groups. Group 1 had a lower level of alanine aminotransferase (ALT) or aspartase aminotransferase (AST) after LTx, less pathological damage, higher concentration of adenosine triphosphate (ATP) and higher microcirculation blood flux in the grafted liver tissue at 1 h after reperfusion than the other two groups. The results primarily showed that 12-h cold preservation was safe, 16 h was unsafe, and 20 h was highly unsafe. But when pentoxifylline was added to UW solution in cold preservation (16-h group, group 4), in contrast to group 2, the incidence of liver tissue necrosis and primary graft nonfunction was significantly lower in group 4 than in group 2. The 1-week survival rate of the pigs was 100% in the former and 20% in latter group. Levels of ALT and AST in recipients' artery blood, malondialdehyde and TNF-alpha concentration in grafted liver tissue, resistance of portal vein and hepatic artery after preservation in group 4 were significantly reduced, whereas microcirculation blood flux of the grafted liver, superoxide dismutase concentration and ATP concentration in grafted liver tissue were significantly elevated.

The safe time limit of cold preservation in UW solution of liver grafts subjected to WI for 20 min was about 12 h and the limits can be prolonged to 16 h when pentoxifylline is added to UW solution. Many mechanisms were involved.