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Primary Study on the Pathogenesis and Intervention of Early Biliary Complications after Liver Transplantation

Author: ZhengShuGuo
Tutor: HeZhenPing;DongJiaHong
School: Third Military Medical University
Course: Surgery
Keywords: Liver transplant Animal models Miniature pigs Biliary complications Ischemia-reperfusion Pentoxifylline
CLC: R657.3
Type: PhD thesis
Year: 2002
Downloads: 178
Quote: 1
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Abstract


The high incidence of biliary complications after liver transplantation, processing difficulties, a direct impact on patient survival and quality of life. In various biliary complications in the early postoperative extrahepatic bile duct necrosis concurrent bile leakage is the most serious type of pathological, can cause graft loss and death receptor, is the need to attach great importance to the field of liver transplantation and problems to be solved. The study found that transplantation bile duct ischemia-reperfusion injury is important etiological factor for liver transplantation biliary complications, early bile duct necrosis, and bile leakage after a long time of warm ischemia and cold preservation of the donor liver bile duct directly reasons. So far, the bile duct of warm ischemia, cold preservation tolerance and transplantation of the liver and gallbladder pipe ischemia-reperfusion injury Although preliminary clinical and experimental evidence has accumulated, transplantation bile duct ischemia tolerance to heat and cold preservation safety time is unclear, yet the lack of effect of ischemia-reperfusion injury in the transplanted liver and gallbladder tube with the exact protective effect of interventions can play in a multi-link. This article was first selected gene homozygosity and high similarity coefficient Bama miniature pigs as experimental subjects, under conditions of non vitro venous bypass successfully established a high degree of standardization, observational study for biliary complications of orthotopic liver transplantation safety time limit of the model, and on this basis transplant hepatobiliary tube tolerance to warm ischemia, cold preservation, transplant hepatobiliary pipe prevention of ischemia-reperfusion injury protection and early postoperative biliary complications preliminary study, the main The results are as follows: 1. Downlink orthotopic liver transplantation in non-veno bypass conditions 20 times the mean operative time was 181 ± 25.8min mean hepatic phase 28.4 ± 3.2min. Anhepatic phase of hemodynamic and metabolic changed dramatically: the MAP never liver early 14.59 ± 1.68kPa fell to 5.87 ± 0.91kPa CVP decreased to 0.27 ± 0.66 ± 0.11kPa 0.10kPa, accompanied by severe acid poisoning and hyperkalemia, pH, BE, cHCO 3 significantly reduced, a significant increase in serum potassium. 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. Animals after surgery the only the intravenous infusion 2d, 1w survival rate of 90%. The day 5,10 organization of the LFTs: after postoperative day 1 ALT, AST was significantly increased and reached a peak in AST and more significantly, three days began to decline, reduced to normal levels in seven days; typical pathological features of biopsy found that the transplanted liver was ischemia-reperfusion injury and recovery process of pathological change, no acute immune rejection. These results suggest that, Bama miniature pigs can be safely tolerated 28.4 ± 3.2 min anhepatic phase, with the recovery of the hepatic blood flow, hemodynamic and metabolic disorders that returned to normal. Died early after liver transplantation bile duct necrosis caused by bile leakage and receptor basis, respectively, discussed 10n five n and 20 n warm ischemia transplantation bile duct security tolerate cold preservation time limit. The results show that the warm ischemia 10min, cold preservation time of less than 16h group, all animals survived lw and early bile duct necrosis and death of the animals; cold preservation time more than 16h significantly increased incidence of early postoperative bile duct necrosis, and due to bile duct necrosis and primary graft non-functional due to receptor death: the incidence of bile duct necrosis gradually increased with the further extension of the cold preservation time, lw survival rate is gradually reduced. When there is a 20min warm ischemia, cold preservation 8h group lw survival rate was 100%, bile duct necrosis; cold save up to 12h, a significant increase in the incidence of bile duct necrosis, bile duct necrosis, and bile leakage due the receptor death; appeared as a further extension of the cold preservation time, primary graft non-functional and surgery, postoperative animals early death, all surviving animals bile duct necrosis occurs. These results suggest that in Under the the 10min heat ischemic conditions, transplant hepatobiliary tube security tolerate cold preservation time limit within 16h, liver graft tolerance under the same conditions the safety of cold preservation time limit within 20h; warm ischemia up to 20n five n transplantation bile duct cold storage time should not exceed 8h, and the the corresponding transplanted liver cold preservation time should not exceed 12h. Transplant hepatobiliary tube ischemia-reperfusion injury no effective protection of the status quo, this study from PTX tube transplanted liver and gallbladder tissue ischemia protective effects and possible mechanisms of reperfusion injury in a preliminary observation, the experimental animals were divided into Lang, IR NS and IR PTX3 group, results showed: IR PTX group, the incidence of the animal bile duct necrosis compared with only, Lang NS group was significantly lower, and not the death of the animal; dish, Lang NS two groups, IR PTX group surgery and all postoperative phase point to a significant decrease in ALT, AST, GGT, ALP, transplant surgery bile duct tissue microcirculatory blood flow GSH content, Na K A TP enzyme, C expansion ten. ATp significantly increased the enzyme activity, MDA content, the number of apoptotic cells and pathomorphological scores were significantly lower. Prompted to save the liquid PTX administered via the hepatic artery, ischemia and reperfusion injury in the transplanted liver and gallbladder tube with a multi-link antagonism, can significantly reduce transplant the bile duct organizations Vll ischemia reperfusion injury, reduce liver transplantation bile duct necrosis incidence of to extend the established warm ischemia donor liver bile duct cold preservation time, resulting in a protective effect on the morphology and function; under our experimental conditions, the increase in the bile duct tissue antioxidant capacity and inhibition of lipid peroxidation, improve tissue micro- circulation, to inhibit bile duct cells apoptosis and maintain the cholangiocyte A Yang enzyme PIX to protect transplanted bile duct ischemia-reperfusion injury. In short, the bypass small pig liver transplantation model has a high degree of standardization, easy to operate, easy to copy, and the advantages of high success rate, good reproducibility and stability, and it overcomes the pig liver transplantation in the past many problem, so that the pig liver transplantation in this complex, difficult surgery has become relatively simple. The model can be excluded animal genetic background and the acute immune rejection factors, more intuitive to show the process of the pathophysiology of ischemia-reperfusion injury, is liver transplantation, transplantation bile duct ischemia-reperfusion injury study ideal animal model. Transplanted liver and bile duct tissue tolerance time limit for cold preservation of security this study revealed different warm ischemia, warm ischemia injury donor liver cold preservation time properly control for clinical liver transplantation reasonable choice to use such for liver provides important basic research information, and for

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