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Liver transplantation is the cure for a variety of end-stage liver disease, the only effective method. Recent years, with surgical techniques, organ preservation, Wai-operative treatment of the progress and the level of awareness of the deepening of the immune response, clinical liver transplantation has achieved great success, but the lack of donor sources with the sharp increase in the number of patients waiting for liver transplantation become increasingly prominent contradiction between supply and demand, the lack of donor liver has become a bottleneck restricting the development of clinical liver transplantation further. Heart-beating donors (NHBD) as a donor source is one important way, is currently attracting much attention. The study found that the NHBD liver transplant recipients with higher primary graft function incidence. Obviously donor warm ischemia, cold ischemia and reperfusion injury is a very important factor, and the greater impact on the immune rejection, as in recent years, cyclosporine, FK506 new potent immune inhibitors development and application of the extent of the impact has been lower. Donor hot and cold ischemic injury beyond its safe time limits will inevitably lead to the NHBD liver transplant failed. But this security time limit is still unclear, and also the lack of able to play in a multi-link effect of interventions for NHBD liver transplantation protection and to prolong graft tolerance to hot and cold ischemia security time limit. This is the first selection of the country improved strains with similar genetic backgrounds the normalized experimental animals - China Bama miniature pigs as experimental subjects, in venous bypass the conditions under the successful establishment of a high degree of standardization, the series of experimental studies for liver transplantation miniature pigs simplify orthotopic liver transplantation model, and on the the NHBD liver transplant graft tolerance based on warm ischemia, cold preservation and safe time limits and cardiac arrest donor liver transplantation donor drugs (PTX) pretreatment on the transplanted liver protective effect, extend the time limit of warm ischemia donor liver withstand cold preservation of security in the preliminary study, the main results are as follows: 1. miniature pigs simplify-orthotopic liver transplantation model making, Total Enforcement liver transplantation 10 cases. The mean operative time was 177.5 ± 13min, mean hepatic phase 31.3 ± 2.7min. Anhepatic phase, hemodynamic and metabolic changed dramatically: the MAP never liver early (14.46 ± 1.86) kPa (4.5 ± 1.58) kPa reduced to CVP from (2.83 ± 0.75) cmH2O (1.00 ± 0.89, down ) cmH2O, heart rate (Hr) significantly accelerated (the faster from 88.2 ± 10.1bpm increase to 175.8 ± 4.0bpm), accompanied by a significant reduction in severe acidosis and hyperkalemia, PH, BE, cHCO3, serum potassium significantly higher. But with the opening up of the blood flow in the portal vein and the inferior vena cava, the hemodynamic and metabolic disorders that gradually returned to normal. The the animal of 1w survival after up to 90%. The results of liver function: one day after the ALT, AST was significantly higher peak, especially AST in three days began to decline, but still significantly higher than the normal level, first lt; WP = 11 gt; -7 days gradually reduced to normal levels; TBIL after 1, 2 and 3 days increased slightly, but still in the normal range within 7 days to return to the preoperative level. After 5,10 days liver biopsy was found that transplanted liver ischemia-reperfusion injury and recovery process pathological changes typical pathological features, no acute immune rejection. These results indicate that the shorter anhepatic phase premise vitro venous bypass can still successfully established the ideal animal liver transplant model. Receptors early postoperative primary graft liver function and lead to death based on analysis infer postoperative liver function (ALT, AST values), liver pathology, microcirculation, reversible hepatic energy metabolism damage results , warm ischemia not simultaneously drive (0,30,45,60 min) after liver transplantation, the donor line in each group one week survival rates were as follows: 100% (5/5), 100% (5/5), 60% (3/5), 20% (1/5). And warm ischemia 0 min group, 30 min group hot 45 min ischemia group, 60 min group in the postoperative ALT and AST values, liver pathology, microcirculation changes hepatic energy metabolism damage and recovery process also significant differences, The first two groups in the extent of damage was significantly lighter than the latter two groups, and easy recovery consistent with postoperative survival. That under our experimental conditions, Bama miniature pig cardiac arrest donor liver transplantation, donor liver tolerance to warm ischemia injury safety time limit of approximately 30 min. This study also further explored the safety time limit cold preservation in UW solution the warm ischemia donor 30min the safety time frame within different time periods (10,20,30 min). The results show that the donor warm ischemia time 10min, UW liquid cooling saved the 20h group after liver transplantation miniature pig one week survival rate was 100%, and save 24,28 h group one week survival rates were 40%, 0%; When the donor warm ischemia time 20 min, UW liquid cooling save one week the 12h group after liver transplantation miniature pig survival rate of 100%, save 16,20 h group one week survival rates were 20%, 0%; donor warm ischemia time of 30min, UW liquid cooling save one week the 6h group after liver transplantation miniature pig survival rate of 100 percent, save 10,14 h group 1 week survival rate were 40%, 0%. Initial cardiac arrest donor liver transplantation, donor hot ischemia time of 30min gradually extend as donor warm ischemic time, that is, until 20,30 min 10min donor liver in UW solution respectively cold preservation 20,12,6 h safer. Further studies have shown that the same warm ischemic conditions with prolonged cold preservation time, reflect hepatic parenchymal cell damage, ALT, AST values ??gradually rise, and reflect hepatic energy metabolism ATP content Quecheng the gradual downward trend hepatic microcirculation blood flow was also a gradual downward trend, morphological results show the extent of cell degeneration, necrosis and ultrastructure damage liver tissue gradually increased, and this change quickly manifested in reperfusion 1h, safety time frame within the group and there are significant differences between the groups other than the security time limit, biochemical, and indicators of hepatic microcirculation changes consistent pathological findings and animal survival, which further confirms the safety conclusions. Prompt cardiac arrest donor liver transplantation should be as short as possible donor warm ischemia time, the maximum should not exceed 30min. Warm ischemia time in less than 10min, the donor liver cold preservation time was extended to 20h transplantation still fight for more donor trimming, transporters and receptors diseased liver resection time; When warm ischemia time of 20min the donor liver cold preservation time should not exceed 12h; warm ischemia time of 30 min, the donor liver cold preservation time should be controlled within the 6h. 4 for the current no can play in a multi-link effect of interventions for NHBD liver transplantation protect and extend lt; WP = 12 gt; the NHBD liver transplant when donor to withstand hot and cold ischemia safety time limit status of the Preliminary Study (PTX) pretreatment of donor drugs shift?
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