The Evaluation Of The Modified HTK Solution And Of The Combination Of Deferoxamine With LK614 In The Preservation Of Rat Livers

Objective: This screening study tested the effects of iron chelators (Deferoxamine and LK-614) supplementation in modified HTK organ preservation solutions on liver function in an orthotopic rat liver transplantation model. To improve the protective effect of HTK solution on the cold ischemic storage and reperfusion, we modified the traditional HTK solution, and used the rat liver transplant model to evaluate the modified solution as comparing it with the traditional HTK solution.Methods: The rat livers underwent a 16hr or 20hr cold ischemic preservation in histidine-tryptophan-ketoglutarate (HTK) or in modified solutions supplemented with or without iron chelators of low (deferoxamine) and high (LK-614) membrane permeability at 4℃. Then the grafts were implanted into the recipient rats using orthotopic liver transplantation technique. The 28-day survival rate of operated rats was observed. Some of the recipients rats were sacrified to assay liver function 28-day post transplantation ,Prothrombin time (PT) was measured by the standard kit . The releases of biochemical markers (GPT, GOT, LDH, Total Bilirubin, and alkaline phosphatase) were measured using a standard kitResults: The supplement of iron chelator Deferoxamine and LK-614 increased the 28-day survival rates. In A type, the long-term survival rates for HTK, mHTK and mHTK++ were 8/10, 6/9, and 5/6 respectively. In B type, the rates severely decreased to: 2/7, 2/9, 3/8. But there were no significantly differences among the three solutions. As for the biochemical markers, mHTK++ group had a tendency of better, but no statistical difference existed among different solutions.Conclusions: Our results suggested that all the three solutions effectively protected the liver from long-term ischemic/reperfusion injury. But the mHTK solution did not show better results than traditional HTK solution. The antioxidants supplement to the mHTK appeared a good outcome, but the difference is statistically no significant difference. Despite studies of using the cultured hepatocytes, liver endothelial cells, the Deferoxamine inhibited the type of injury which had shown better results, it is worthy to further study the base solution with optimized chelator concentration.