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Primary Study On The Pathogenesis And Intervention Of Early Biliary Complications After Liver Transplantation

Posted on:2003-09-02Degree:DoctorType:Dissertation
Country:ChinaCandidate:S G ZhengFull Text:PDF
GTID:1104360095461214Subject:Surgery
Abstract/Summary:PDF Full Text Request
Biliary complications occur frequently following liver transplantation and are associated with patients' survival and quality of life. Among all types of biliary complications, necrosis of bile duct accompanied by leakage is the most severe one in the early posttransplantation period which can lead to graft loss and recipients death.Many studies have suggested that ischemia-reperfusion(IR) injuries are the major etiological factors of biliary complications following liver transplantation and prolonged warm ischemia and cold storage time are the direct causes for early biliary necrosis and leakage. By now, although primary experiences are available on the tolerance study of bile duct to warm ischemia and cold preservation and on the prevention of ischemia reperfusion-mediated injury of bile duct during liver transplantation, the tolerance time limit of bile duct to warm ischemia and cold preservation remains unknown and effective measures against liver transplantation-related biliary injuries are lacking.Miniature swines with more genetical homogeneity and high coefficience of similarity were used in the experiments to establish orthotopic liver transplantation(OLT) model without veno-venous bypass. The tolerance time limits of ischemia and preservation and intervention of IR injuries of bile duct during the early period after liver transplantation were investigated. The results showed that:1. 20 OLTs were performed between pairs of miniature pigs. The mean operation time and anhepatic phase was 181#25.8 and 28.4#3.2 minutes respectively. During the anhepatic phase, dramatic hemodynamic andmetabolism changes accompanied by severe acidosis, hyperkalemia were identified. MAP and CVP decreased from 14.59 + 1.68 and 0.66?.11kPa to 5.87?.91 and 0.27 + 0.10 kPa respectively, while pH, BE and cHCO3 were significantly reduced. After reperfusion, the disorder of hemodynamics and metabolism described above were recovered gradually. The animals received transfuse for only two days and regained normal life activity. 1-week survival rate was 90%. Liver function tests showed concentrations of AST and ALT were significantly increased and reached the peak level on postoperative 1 day, especially that of AST. From postoperative 3 day, AST and ALT began to decrease and reached normal level on postoperative 7 day. On postoperative 5 and 10 day, hepatic biopsies revealed mild IR injuries and the subsequent changes in the graft. No typical pathological changes of acute rejection were observed. The results suggested that miniature pigs were able to tolerate anhepatic phase of 28.4+3.2 minutes. Hemodynamics and metabolism changes recovered following the reperfusion.2. To study the tolerance time limits of the bile duct to warm ischemia and cold preservation, the above established OLT models were adopted and necrosis of bile duct and the related bile leakage and recipient death were used as the standards for evaluating the tolerance time limits.The results showed that after 10 minutes of warm ischemia followed by less than 16 hours of cold preservation, all animals could survive 1 week and there was no necrosis of bile duct and animal death. However, as long as the cold preversation time exceeded 16 hours, the incidence of biliary necrosis was significantly increased, and recipient death from biliary necrosis and primary graft nonfunction occurred, the 1-week survival rate of the animals was decreased significantly. When the graft was subjected to 20 minutes of warm ischemia followed by 8 hours of cold preservation, the 1-week survival rate of the pigs was 100% and no biliarynecrosis was found. But when the cold preservation time is more than 12 hours,the incidence of biliary necrosis was significantly increased, and recipient death from bile leaks occurred, with the prolongation of the cold preservation, primary graft nonfunction and intraoperative or early postoperative death occurred, the living animals all developed biliary necrosis. It is concluded that under the condition of 10 and 20 minutes of warm i...
Keywords/Search Tags:Liver transplantation, Animal model, Biliary complications, Ischemia reperfusion, Pentoxifylline, Miniature pigs
PDF Full Text Request
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