BACKGROUND: Although the use of non-heart beating donors (NHBDs) could bridge the widening gap between organ demand and supply, its application to liver transplantation is limited due to the high incidence of primary ...BACKGROUND: Although the use of non-heart beating donors (NHBDs) could bridge the widening gap between organ demand and supply, its application to liver transplantation is limited due to the high incidence of primary graft loss. Prevention of liver injury in NHBDs will benefit the results of transplantation. This study was conducted to evaluate the protective effects of L-arginine on liver grafts from NHBDs. METHODS: One hundred and four Wistar rats were randomly divided into 7 groups: normal control (n=8) controls 1, 2 and 3 (C-1, C-2, C-3, n=16), and experimental 1, 2 and 3 (E-1, E-2, E-3, n=16). For groups C-1 and E-1, C-2 and E-2, and C-3 and E-3, the warm ischemia time was 0, 30, and 45 minutes, respectively. Liver grafts were flushed with and preserved in 4 degrees C Euro-collins solution containing 1 mmol/L L-arginine for 1 hour in each experimental group. Recipients of each experimental group were injected with L-arginine (10 mg/kg body weight) by tail vein 10 minutes before portal vein reperfusion. Donors and recipients of each experimental control group were treated with normal saline. Then transplantation was performed. At 1, 3, and 24 hours after portal vein reperfusion, blood samples were obtained to determine the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), nitric oxide (NO) and plasma endothelin (ET). At 3 hours after portal vein reperfusion, grafts samples were fixed in 2.5% glutaraldehyde for electron microscopic observation. RESULTS: At I hour after portal vein reperfusion, the levels of NO in groups E-1, E-2, E-3 and C-1, C-2, C-3 were lower, while the levels of plasma ET, serum ALT and AST were higher than those in the normal control group (P<0.05). At 1, 3, and 24 hours, the levels of NO in groups E-1, E-2, E-3 were higher, while the levels of plasma ET, serum ALT and AST were lower than those in the corresponding control groups (C-1, C-2, C-3) (P<0.05). The levels of NO in groups C-2 and C-3 were lower than in group C-1 (P<0.05), and the level of NO in group C-3 was lower than in group C-2 (P<0.05). At 1, 3 and 24 hours, the levels of plasma ET, serum ALT, and AST in groups E-1, E-2, E-3 were lower than those in the corresponding control groups (C-1, C-2, C-3) (P<0.05). The levels of plasma ET, serum ALT, and AST were lower in group C-3 than in groups C-1 and C-2 (P<0.05). Pathological changes in groups E-1, E-2, E-3 were milder than those in the corresponding experimental control groups (C-1, C-2, C-3). CONCLUSIONS: The imbalance between NO and ET plays an important role in the development of ischemia-reperfusion injury of liver grafts from NHBDs. L-arginine can attenuate injury in liver grafts from NHBDs by improving the balance between NO and ET.展开更多
BACKGROUND: Liver transplantation is an effective treatment for end-stage liver disease, but a huge gap remains between the number of people who need a liver transplant and the number of organs available. In order to ...BACKGROUND: Liver transplantation is an effective treatment for end-stage liver disease, but a huge gap remains between the number of people who need a liver transplant and the number of organs available. In order to maximize donor organ access for adult and pediatric recipients, novel surgical and liver replacement procedures have evolved. Newer surgical techniques include split cadaveric liver transplantation and living donor liver transplantation (LDLT). With marginal and abnormal donor livers, despite tremendous advances in surgical technology, individual surgical procedure can not be completely brought into play unless effective measurements and basal studies are undertaken. DATA SOURCES: A literature search of MEDLINE and the Web of Science database using 'liver transplantation' and 'expanding donor pool' was conducted and research articles were reviewed. RESULTS: Therapies directed toward scavenging O(2-), inhibiting nicotinamide adenine dinucleotide phosphate oxidase, and/or immuno-neutralizing tumor necrosis factor-alpha may prove useful in limiting the liver injury induced by surgical procedures such as split liver transplantation or LDLT. Improved donor organ perfusion and preservation methods, modulation of inflammatory cytokines, energy status enhancement, microcirculation amelioration, and antioxidant usage can improve non-heart beating donor liver transplantation. Effective measures have been taken to improve the local conditions of donor cells with steatosis, including usage of fat-derived hormone and inflammatory mediators, ischemic preconditioning, depletion of Kupffer cells, and cytokine antibody and gene therapy. Double-filtration plasmapheresis can effectively reduce HCV viremia and prevent HCV recurrence in patient with high HCV RNA levels after LDLT. CONCLUSIONS: Shortage of grafts and poor function of marginal and abnormal donor grafts put many patients at risk of death in waiting for liver transplantation. Advances in surgical technology, combined with improvement and breakthroughs in basic studies hold a promise in expanding the liver donor pool.展开更多
INTRODUCTIONThe last two decades of the twentieth century havewitnessed increasingly successful rates of livertransplantation.The number of liver transplantations hasincreased steadily while the number of organ donors
Background Non-heart-beating donor lung has been a promising source of lung transplantation. Many studies on non-heart-beating donor lungs are based on animal lung transplantation. In this study, we assessed by organ ...Background Non-heart-beating donor lung has been a promising source of lung transplantation. Many studies on non-heart-beating donor lungs are based on animal lung transplantation. In this study, we assessed by organ bath the effect of one-hour warm ischemia on the non-heart-beating donor lung in terms of the integrity of contractile and relaxant functions and tissue structures of pulmonic arteries and bronchi. Methods Sixteen Swedish pigs were randomly classified into two groups： heart-beating donor group and 1-hour warm ischemia non-heart-beating donor group. Pulmonic and bronchial rings were taken from the isolated left lungs of the pigs. The pulmonic rings were stimulated by U-46619 （5.7 mol/L） and acetylcholine （104 mmol/L） to assess the contractile abilities of smooth muscle and the endothelium-dependent relaxation response, respectively. As such, acetylcholine （10^-5 mmol/L） and natrium arachidonic acid （0.01%） were used to detect the contraction of bronchial smooth muscle and epithelium-dependent relaxation response. Meanwhile, the variances of precontraction tension of control groups were recorded to measure whether there was spontaneous relaxation during endothelium/epithelium-dependent relaxation course. Finally, papaverine solution （10.4 mmol/L） was used to detect the non-endothelium/epithelium-dependent relaxant abilities of pulmonic and bronchial smooth muscles. Results There was no significant difference in the tension values of precontraction of pulmonic rings （P 〉0.05）, endothelium-dependent relaxation （P 〉0.05）, precontraction of bronchial rings （P 〉0.05） and epithelium-dependent relaxation （P 〉0.05） between the heart-beating donor group and the 1-hour warm ischemia non-heart-beating donor group. And the pulmonic and bronchial rings of each subgroup B had no spontaneous relaxation. Finally, papaverine solution relaxed the smooth muscle of all the rings completely. Conclusions The results of this experiment suggest that the contractile and relaxant functions and tissue structures of pulmonic arteries and bronchi are not damaged after warm ischemia for 1 hour, and support the further study of non-heart-beating donor lung.展开更多
Orthotopic liver transplantation ( OLT) has evolved over the last forty years from an experimental endeavor to standard of care therapy for many patients with end stage hepatic disease. Many technical advances have co...Orthotopic liver transplantation ( OLT) has evolved over the last forty years from an experimental endeavor to standard of care therapy for many patients with end stage hepatic disease. Many technical advances have contributed to the current success of OLT, but surgical complications, especially involving the biliary reconstruction, remain a morbid problem. Biliary complications after OLT include leaks and strictures. Strictures may be anastoinotic or intrahepatic and diffuse, as seen in cases of hepatic artery thrombosis. Current efforts to expand the limited donor pool include the use of non-heart beating donors. The organ procurement process in these donors entails an increased period of warm ischemia and results with non-heart beating donor grafts have been mixed. It is now appreciated that there is an increased incidence of subsequent diffuse biliary stricturing or ' ischemic cholangiopathy' in recipients of these organs. Animal models of this phenomenon and potential therapeutic strategies targeted at ischemic cholangiopathy are being developed with potential applicability to non-heart beating donation and will be the focus of this review.展开更多
基金a grant from the Science & Technology Development Foundation of Guangdong Health Bureau(No.2006345).
文摘BACKGROUND: Although the use of non-heart beating donors (NHBDs) could bridge the widening gap between organ demand and supply, its application to liver transplantation is limited due to the high incidence of primary graft loss. Prevention of liver injury in NHBDs will benefit the results of transplantation. This study was conducted to evaluate the protective effects of L-arginine on liver grafts from NHBDs. METHODS: One hundred and four Wistar rats were randomly divided into 7 groups: normal control (n=8) controls 1, 2 and 3 (C-1, C-2, C-3, n=16), and experimental 1, 2 and 3 (E-1, E-2, E-3, n=16). For groups C-1 and E-1, C-2 and E-2, and C-3 and E-3, the warm ischemia time was 0, 30, and 45 minutes, respectively. Liver grafts were flushed with and preserved in 4 degrees C Euro-collins solution containing 1 mmol/L L-arginine for 1 hour in each experimental group. Recipients of each experimental group were injected with L-arginine (10 mg/kg body weight) by tail vein 10 minutes before portal vein reperfusion. Donors and recipients of each experimental control group were treated with normal saline. Then transplantation was performed. At 1, 3, and 24 hours after portal vein reperfusion, blood samples were obtained to determine the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), nitric oxide (NO) and plasma endothelin (ET). At 3 hours after portal vein reperfusion, grafts samples were fixed in 2.5% glutaraldehyde for electron microscopic observation. RESULTS: At I hour after portal vein reperfusion, the levels of NO in groups E-1, E-2, E-3 and C-1, C-2, C-3 were lower, while the levels of plasma ET, serum ALT and AST were higher than those in the normal control group (P<0.05). At 1, 3, and 24 hours, the levels of NO in groups E-1, E-2, E-3 were higher, while the levels of plasma ET, serum ALT and AST were lower than those in the corresponding control groups (C-1, C-2, C-3) (P<0.05). The levels of NO in groups C-2 and C-3 were lower than in group C-1 (P<0.05), and the level of NO in group C-3 was lower than in group C-2 (P<0.05). At 1, 3 and 24 hours, the levels of plasma ET, serum ALT, and AST in groups E-1, E-2, E-3 were lower than those in the corresponding control groups (C-1, C-2, C-3) (P<0.05). The levels of plasma ET, serum ALT, and AST were lower in group C-3 than in groups C-1 and C-2 (P<0.05). Pathological changes in groups E-1, E-2, E-3 were milder than those in the corresponding experimental control groups (C-1, C-2, C-3). CONCLUSIONS: The imbalance between NO and ET plays an important role in the development of ischemia-reperfusion injury of liver grafts from NHBDs. L-arginine can attenuate injury in liver grafts from NHBDs by improving the balance between NO and ET.
基金supported by a grant from the Science and Technology Commission of Zhejiang Province, China (2006C13020)
文摘BACKGROUND: Liver transplantation is an effective treatment for end-stage liver disease, but a huge gap remains between the number of people who need a liver transplant and the number of organs available. In order to maximize donor organ access for adult and pediatric recipients, novel surgical and liver replacement procedures have evolved. Newer surgical techniques include split cadaveric liver transplantation and living donor liver transplantation (LDLT). With marginal and abnormal donor livers, despite tremendous advances in surgical technology, individual surgical procedure can not be completely brought into play unless effective measurements and basal studies are undertaken. DATA SOURCES: A literature search of MEDLINE and the Web of Science database using 'liver transplantation' and 'expanding donor pool' was conducted and research articles were reviewed. RESULTS: Therapies directed toward scavenging O(2-), inhibiting nicotinamide adenine dinucleotide phosphate oxidase, and/or immuno-neutralizing tumor necrosis factor-alpha may prove useful in limiting the liver injury induced by surgical procedures such as split liver transplantation or LDLT. Improved donor organ perfusion and preservation methods, modulation of inflammatory cytokines, energy status enhancement, microcirculation amelioration, and antioxidant usage can improve non-heart beating donor liver transplantation. Effective measures have been taken to improve the local conditions of donor cells with steatosis, including usage of fat-derived hormone and inflammatory mediators, ischemic preconditioning, depletion of Kupffer cells, and cytokine antibody and gene therapy. Double-filtration plasmapheresis can effectively reduce HCV viremia and prevent HCV recurrence in patient with high HCV RNA levels after LDLT. CONCLUSIONS: Shortage of grafts and poor function of marginal and abnormal donor grafts put many patients at risk of death in waiting for liver transplantation. Advances in surgical technology, combined with improvement and breakthroughs in basic studies hold a promise in expanding the liver donor pool.
基金Shanghai Science and Technology Development Fund,№964119027.
文摘INTRODUCTIONThe last two decades of the twentieth century havewitnessed increasingly successful rates of livertransplantation.The number of liver transplantations hasincreased steadily while the number of organ donors
文摘Background Non-heart-beating donor lung has been a promising source of lung transplantation. Many studies on non-heart-beating donor lungs are based on animal lung transplantation. In this study, we assessed by organ bath the effect of one-hour warm ischemia on the non-heart-beating donor lung in terms of the integrity of contractile and relaxant functions and tissue structures of pulmonic arteries and bronchi. Methods Sixteen Swedish pigs were randomly classified into two groups： heart-beating donor group and 1-hour warm ischemia non-heart-beating donor group. Pulmonic and bronchial rings were taken from the isolated left lungs of the pigs. The pulmonic rings were stimulated by U-46619 （5.7 mol/L） and acetylcholine （104 mmol/L） to assess the contractile abilities of smooth muscle and the endothelium-dependent relaxation response, respectively. As such, acetylcholine （10^-5 mmol/L） and natrium arachidonic acid （0.01%） were used to detect the contraction of bronchial smooth muscle and epithelium-dependent relaxation response. Meanwhile, the variances of precontraction tension of control groups were recorded to measure whether there was spontaneous relaxation during endothelium/epithelium-dependent relaxation course. Finally, papaverine solution （10.4 mmol/L） was used to detect the non-endothelium/epithelium-dependent relaxant abilities of pulmonic and bronchial smooth muscles. Results There was no significant difference in the tension values of precontraction of pulmonic rings （P 〉0.05）, endothelium-dependent relaxation （P 〉0.05）, precontraction of bronchial rings （P 〉0.05） and epithelium-dependent relaxation （P 〉0.05） between the heart-beating donor group and the 1-hour warm ischemia non-heart-beating donor group. And the pulmonic and bronchial rings of each subgroup B had no spontaneous relaxation. Finally, papaverine solution relaxed the smooth muscle of all the rings completely. Conclusions The results of this experiment suggest that the contractile and relaxant functions and tissue structures of pulmonic arteries and bronchi are not damaged after warm ischemia for 1 hour, and support the further study of non-heart-beating donor lung.
文摘Orthotopic liver transplantation ( OLT) has evolved over the last forty years from an experimental endeavor to standard of care therapy for many patients with end stage hepatic disease. Many technical advances have contributed to the current success of OLT, but surgical complications, especially involving the biliary reconstruction, remain a morbid problem. Biliary complications after OLT include leaks and strictures. Strictures may be anastoinotic or intrahepatic and diffuse, as seen in cases of hepatic artery thrombosis. Current efforts to expand the limited donor pool include the use of non-heart beating donors. The organ procurement process in these donors entails an increased period of warm ischemia and results with non-heart beating donor grafts have been mixed. It is now appreciated that there is an increased incidence of subsequent diffuse biliary stricturing or ' ischemic cholangiopathy' in recipients of these organs. Animal models of this phenomenon and potential therapeutic strategies targeted at ischemic cholangiopathy are being developed with potential applicability to non-heart beating donation and will be the focus of this review.
