| Liver transplantation has been widely accepted as an effective treatment for end-stage liver disease.Refinements in surgical techniques,organ preservation,patient management, and understanding of the immune responses have significantly expanded the application of liver transplantation in recent years.A serious shortage of donor organs has limited its clinical application.To increase the number of livers available for liver transplantation,graft procurement from non-heart-beating donors(NHBDs)has again become the focus of attention.Although successful kidney transplantations have been reported with organs procured from NHBDs, less encouraging results have been observed in liver transplantation.It is found that the incidence rate of primary liver graft nonfunction after operation was high for NHBDs liver transplantation.Warm ischemia or cold ischemia or ischemia-reperfusion injury of the grafts are considered as main risk factors for postoperative grafts dysfunction afer NHBDs liver transplantation. In contrast,the immune rejection regarded as once the most important risk factor has seldom lead to graft dysfunction, as many new immunosuppressants(Cyclosporine , FK506 and so on) are developed and used in liver transplantation. Prolonged warm ischemia and cold storage time are the direct causes for early primary liver graft nonfunction .But the tolerance limits of liver grafts to warm or cold ischemia are yet unknown in NHBDs liver transplantation until now. The effective measures against liver transplantation-related warm ischemia injury , cold ischemia injury and ischemia-reperfusion injury are still lacking.Methods that can protect the grafts agaist warm or cold ischemia of the grafts are urgently needed when NHBDs liver transplantation are performed. In our experiments, a simplified orthotopic liver transplantation(OLT) model without Venovenous bypass(VVB) in Guangxi BAMA miniature swine has been successfully developed and evaluated in term of morbidity and mortality. Basing this model,the tolerance time limits to warm ischemia and cold preservation in UW solution of the liver grafts were investigated. Then the effect of 'liver-graft-drug(PTX) -preconditioning' onwarm ischemia and preservation/reperfusion injuries of grafted liver during the early period after liver transplantation was investigated and the effectiveness of the mothed on the prolongation tolerance limits to warm or cold ischemia of the liver graft was also evaluated. The results showed:1. Ten OLTs were performed between pairs of Guangxi BAMA miniature swine(3-6months of age,8-11Kg).In the donors, the liver freeing , cold perfusion in situ ,hepatectomy and preserving of the liver in UW solution was performed by routine method,200ml of blood was taken from the donor for transfusing to the recipient in the liver transplantation operation. In the recipient, after total hepatectomy and complete portal and caval clamping,the suprahepatic vena cava and portal vein were sutured without VVB, after that, the liver graft was perfused.Then infrahepatic vena cava,hepatic artery and biliary reconstruction were performed with end-to-end sutures. The mean operation time and anhepatic phase duration were 177.5±13min and 31.3±2.67 minutes respectively. During the anhepatic phase,dramatic hemodynamic and metabolism changes accompanied by severe acidosis, hyperkalemia were identified.MAP and CVP decreased from 14.46±1.86 kPa and 2.83±0.75cmH2O to 4.5±1.58kPa and 1.00±0.89cmH2O respectively.pH, BE and cHCO3 were significantly reduced,too.After reperfusion, the hemodynamic status recovered promptly and became stable gradually. 90% (9/10) of the animals survived more than 1 week. 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 4-7 day. TBIL was increased on postoperative 1-3 day and reached normal level on postoperative 4-7 da... |