AIM: To optimize the perfusates used for hypothermicmachine perfusion(HMP).METHODS: Sprague-Dawley rats were assigned randomly to three groups(n = 12 per group) that received either saline, University of Wisconsin col...AIM: To optimize the perfusates used for hypothermicmachine perfusion(HMP).METHODS: Sprague-Dawley rats were assigned randomly to three groups(n = 12 per group) that received either saline, University of Wisconsin coldstorage solution(UW) or histidine-tryptophan-ketoglutarate solution(HTK) as the perfusate. Each group was divided into two subgroups: static cold storage(SCS) and HMP(n = 6 per subgroup). The liver graft was retrieved according to the method described by Kamada. For the SCS group, the graft was directly placed into cold perfusate(0-4?℃) for 6 h after liver isolation while the portal vein of the graft was connected to the perfusion machine for the HMP group. Then the perfusates were collected at different time points for analysis of aspartate aminotransferase(AST), alanine transaminase(ALT) and lactate dehydrogenase(LDH) levels. Liver tissues were obtained for evaluation of histology, dry/wet weight(D/W) ratio, and malondialdehyde(MDA) and adenosine-triphosphate(ATP) levels. The portal vein pressure and velocity were monitored in real time in all HMP subgroups.RESULTS: Comparison of HMP and SCS: Regardless of the perfusate, HMP improved the architecture of donor graft in reducing the congestion around sinusoids and central vein and maintaining sinusoid lining in morphology; HMP improved liver function in terms of ALT, AST and LDH, especially during the 3-6 h period(SCS vs HMP using saline: ALT3, 225.00 ± 105.62 vs 49.50 ± 18.50, P = 0.047; LDH3, 1362.17 ± 563.30 vs 325.75 ± 147.43, P = 0.041; UW: LDH6, 2880.14 ± 948.46 vs 2135.00 ± 174.27, P = 0.049; HTK, AST6, 307.50 ± 52.95 vs 185.20 ± 20.46, P = 0.041); HMP decreased MDA level(saline, 2.79 ± 0.30 vs 1.09 ± 0.09, P = 0.008; UW, 3.01 ± 0.77 vs 1.23 ± 0.68, P = 0.005; HTK, 3.30 ± 0.52 vs 1.56 ± 0.22, P = 0.006). Comparison among HMP subgroups: HTK showed less portal vein resistance than UW and saline(vs saline, 3.41 ± 0.49 vs 5.00 ± 0.38, P < 0.001; vs UW, 3.41 ± 0.49 vs 4.52 ± 0.63, P = 0.007); UW reduced edema most efficiently(v展开更多
AIM To compare the effect of University of Wisconsin(UW) solution with or without metformin, an AMP-activated protein kinase(AMPK) activator, for preserving standard and marginal liver grafts of young and aged rats ex...AIM To compare the effect of University of Wisconsin(UW) solution with or without metformin, an AMP-activated protein kinase(AMPK) activator, for preserving standard and marginal liver grafts of young and aged rats ex vivo by hypothermic machine perfusion(HMP).METHODS Eighteen young(4 mo old) and 18 aged(17 mo old)healthy male SD rats were selected and randomly divided into three groups: control group, UW solution perfusion group(UWP), and UW solution with metformin perfusion group(MUWP). Aspartate aminotransferase(AST), alanine aminotransferase(ALT), lactate dehydrogenase(LDH), interleukin-18(IL-18), and tumor necrosis factor-alpha(TNF-α) in the perfused liquid were tested. The expression levels of AMPK and endothelial nitric oxide synthase(e NOS) in liver sinusoidal endothelial cells were also examined.Additionally, microscopic evaluation of the harvested perfused liver tissue samples was done. RESULTS AST, ALT, LDH, IL-18 and TNF-α levels in the young and aged liver-perfused liquid were, respectively,significantly lower in the MUWP group than in the UWP group(P < 0.05), but no significant differences were found between the young and aged MUWP groups.Metformin increased the expression of AMPK and e NOS protein levels, and promoted the extracellular release of nitric oxide through activation of the AMPK-e NOS mediated pathway. Histological examination revealed that in the MUWP group, the extent of liver cells and tissue damage was significantly reduced compared with the UWP group.CONCLUSION The addition of metformin to the UW preservative solution for ex vivo HMP can reduce rat liver injury during cold ischemia, with significant protective effects on livers, especially of aged rats.展开更多
The scarcity of donor livers has increased the interest in donation after cardiac death(DCD) as an additional pool to expand the availability of organs. However, the initial results of liver transplantation with DCD g...The scarcity of donor livers has increased the interest in donation after cardiac death(DCD) as an additional pool to expand the availability of organs. However, the initial results of liver transplantation with DCD grafts have been suboptimal due to an increased rate of complications, as well as decreased graft survival. These challenges have led to many developments in DCD donation outcome, as well as basic and translational research. In this article we review the unique characteristics of DCD donors, nuances of DCD organ procurement, the effect of prolonged warm and cold ischemia times, and discuss major studies that compared DCD to donation after brain death liver transplantation, in terms of outcomes and complications. We also review the different methods of donor treatment that has been applied to ameliorate DCD organ outcome, and we discuss the role of machine perfusion techniques in organ reconditioning. We discuss the two major perfusionmodels, namely, hypothermic machine perfusion and normothermic machine perfusion; we compare both methods, and delineate their major differences.展开更多
目的评价国内外文献报道的肾脏低温机械灌注(HMP)与静态冷保存(CS)的医疗费用,为临床决策提供参考。方法检索PubMed、CENTRAL(Cochrane Library)、Web of Science、EMBASE、CNKI、万方等所有肾脏HMP与CS的医疗费用对比的文献。根据纳入...目的评价国内外文献报道的肾脏低温机械灌注(HMP)与静态冷保存(CS)的医疗费用,为临床决策提供参考。方法检索PubMed、CENTRAL(Cochrane Library)、Web of Science、EMBASE、CNKI、万方等所有肾脏HMP与CS的医疗费用对比的文献。根据纳入和排除标准对搜索到的文献进行筛选以确定符合条件的文献。提取并分析文献中HMP和CS费用的数据,以描述性方式报告结果。结果共纳入10篇报道HMP和CS费用的文献。结果显示,在扩大标准供肾组中,HMP相比CS首次住院费用更低。HMP相比CS可能长期费用更低。其费用低可能与移植肾功能延迟(DGF)发生率降低有关。结论HMP可以带来医学和经济学效益,HMP相比CS的费用优势可能与供肾质量改善以及DGF发生率降低有关。展开更多
目的探究他克莫司(FK506)联合低温机械灌注能否具有对大鼠肝脏移植缺血再灌注损伤的保护作用。方法将大鼠分为HTK液机械灌注(HTK)组和FK506+HTK液机械灌注(FK506+HTK)组,取出HTK液机械灌注组供体肝脏后,在4℃,150 mL HTK液状态下灌注3 ...目的探究他克莫司(FK506)联合低温机械灌注能否具有对大鼠肝脏移植缺血再灌注损伤的保护作用。方法将大鼠分为HTK液机械灌注(HTK)组和FK506+HTK液机械灌注(FK506+HTK)组,取出HTK液机械灌注组供体肝脏后,在4℃,150 mL HTK液状态下灌注3 h后进行原位肝移植,FK506+HTK组供肝在4℃,FK506+150 mL HTK液灌注3 h后进行原位肝移植,两组移植后3和24 h取血,离心得血清,采用生化自动分析仪测定肝功能;移植后24 h麻醉取肝脏组织,甲醛固定进行HE染色,进行病理学观察。结果FK506+HTK组ALT水平低于HTK组(P<0.05),FK506+HTK组炎性因子浸润较HTK液组减少,肝细胞结构完整;FK506+HTK组炎性因子浸润较HTK液组减少,肝细胞结构完整。结论FK506加入到灌注液中对供肝进行机械灌注,在移植后3 h内有效减少肝脏肝功能损伤和炎性损伤,对肝脏有一定的保护作用。展开更多
基金Supported by National Science and Technology Major Project,No.2012ZX10002-017Natural Science Foundation of China for Innovative Research Group,No.81121002+4 种基金National Natural Science Foundation of China,No.81000137 and No.81470891The Qianjiang Talent Program of Zhejiang Province,China,No.2012R10045the Scientific Research Program for the Returned Overseas Chinese Scholars,Ministry of Health,China,No.J20112008National High Technology Research and Development Program of China for Young Scientists(863 Program),No.2015AA020923Ministry of Education,Zhejiang Province,China,No.Y201328095
文摘AIM: To optimize the perfusates used for hypothermicmachine perfusion(HMP).METHODS: Sprague-Dawley rats were assigned randomly to three groups(n = 12 per group) that received either saline, University of Wisconsin coldstorage solution(UW) or histidine-tryptophan-ketoglutarate solution(HTK) as the perfusate. Each group was divided into two subgroups: static cold storage(SCS) and HMP(n = 6 per subgroup). The liver graft was retrieved according to the method described by Kamada. For the SCS group, the graft was directly placed into cold perfusate(0-4?℃) for 6 h after liver isolation while the portal vein of the graft was connected to the perfusion machine for the HMP group. Then the perfusates were collected at different time points for analysis of aspartate aminotransferase(AST), alanine transaminase(ALT) and lactate dehydrogenase(LDH) levels. Liver tissues were obtained for evaluation of histology, dry/wet weight(D/W) ratio, and malondialdehyde(MDA) and adenosine-triphosphate(ATP) levels. The portal vein pressure and velocity were monitored in real time in all HMP subgroups.RESULTS: Comparison of HMP and SCS: Regardless of the perfusate, HMP improved the architecture of donor graft in reducing the congestion around sinusoids and central vein and maintaining sinusoid lining in morphology; HMP improved liver function in terms of ALT, AST and LDH, especially during the 3-6 h period(SCS vs HMP using saline: ALT3, 225.00 ± 105.62 vs 49.50 ± 18.50, P = 0.047; LDH3, 1362.17 ± 563.30 vs 325.75 ± 147.43, P = 0.041; UW: LDH6, 2880.14 ± 948.46 vs 2135.00 ± 174.27, P = 0.049; HTK, AST6, 307.50 ± 52.95 vs 185.20 ± 20.46, P = 0.041); HMP decreased MDA level(saline, 2.79 ± 0.30 vs 1.09 ± 0.09, P = 0.008; UW, 3.01 ± 0.77 vs 1.23 ± 0.68, P = 0.005; HTK, 3.30 ± 0.52 vs 1.56 ± 0.22, P = 0.006). Comparison among HMP subgroups: HTK showed less portal vein resistance than UW and saline(vs saline, 3.41 ± 0.49 vs 5.00 ± 0.38, P < 0.001; vs UW, 3.41 ± 0.49 vs 4.52 ± 0.63, P = 0.007); UW reduced edema most efficiently(v
基金Supported by the National Natural Science Foundation,No.81470896the Project of Development and Innovation Team of Ministry of Education,No.IRT_16R57
文摘AIM To compare the effect of University of Wisconsin(UW) solution with or without metformin, an AMP-activated protein kinase(AMPK) activator, for preserving standard and marginal liver grafts of young and aged rats ex vivo by hypothermic machine perfusion(HMP).METHODS Eighteen young(4 mo old) and 18 aged(17 mo old)healthy male SD rats were selected and randomly divided into three groups: control group, UW solution perfusion group(UWP), and UW solution with metformin perfusion group(MUWP). Aspartate aminotransferase(AST), alanine aminotransferase(ALT), lactate dehydrogenase(LDH), interleukin-18(IL-18), and tumor necrosis factor-alpha(TNF-α) in the perfused liquid were tested. The expression levels of AMPK and endothelial nitric oxide synthase(e NOS) in liver sinusoidal endothelial cells were also examined.Additionally, microscopic evaluation of the harvested perfused liver tissue samples was done. RESULTS AST, ALT, LDH, IL-18 and TNF-α levels in the young and aged liver-perfused liquid were, respectively,significantly lower in the MUWP group than in the UWP group(P < 0.05), but no significant differences were found between the young and aged MUWP groups.Metformin increased the expression of AMPK and e NOS protein levels, and promoted the extracellular release of nitric oxide through activation of the AMPK-e NOS mediated pathway. Histological examination revealed that in the MUWP group, the extent of liver cells and tissue damage was significantly reduced compared with the UWP group.CONCLUSION The addition of metformin to the UW preservative solution for ex vivo HMP can reduce rat liver injury during cold ischemia, with significant protective effects on livers, especially of aged rats.
文摘The scarcity of donor livers has increased the interest in donation after cardiac death(DCD) as an additional pool to expand the availability of organs. However, the initial results of liver transplantation with DCD grafts have been suboptimal due to an increased rate of complications, as well as decreased graft survival. These challenges have led to many developments in DCD donation outcome, as well as basic and translational research. In this article we review the unique characteristics of DCD donors, nuances of DCD organ procurement, the effect of prolonged warm and cold ischemia times, and discuss major studies that compared DCD to donation after brain death liver transplantation, in terms of outcomes and complications. We also review the different methods of donor treatment that has been applied to ameliorate DCD organ outcome, and we discuss the role of machine perfusion techniques in organ reconditioning. We discuss the two major perfusionmodels, namely, hypothermic machine perfusion and normothermic machine perfusion; we compare both methods, and delineate their major differences.
文摘目的评价国内外文献报道的肾脏低温机械灌注(HMP)与静态冷保存(CS)的医疗费用,为临床决策提供参考。方法检索PubMed、CENTRAL(Cochrane Library)、Web of Science、EMBASE、CNKI、万方等所有肾脏HMP与CS的医疗费用对比的文献。根据纳入和排除标准对搜索到的文献进行筛选以确定符合条件的文献。提取并分析文献中HMP和CS费用的数据,以描述性方式报告结果。结果共纳入10篇报道HMP和CS费用的文献。结果显示,在扩大标准供肾组中,HMP相比CS首次住院费用更低。HMP相比CS可能长期费用更低。其费用低可能与移植肾功能延迟(DGF)发生率降低有关。结论HMP可以带来医学和经济学效益,HMP相比CS的费用优势可能与供肾质量改善以及DGF发生率降低有关。
文摘目的探究他克莫司(FK506)联合低温机械灌注能否具有对大鼠肝脏移植缺血再灌注损伤的保护作用。方法将大鼠分为HTK液机械灌注(HTK)组和FK506+HTK液机械灌注(FK506+HTK)组,取出HTK液机械灌注组供体肝脏后,在4℃,150 mL HTK液状态下灌注3 h后进行原位肝移植,FK506+HTK组供肝在4℃,FK506+150 mL HTK液灌注3 h后进行原位肝移植,两组移植后3和24 h取血,离心得血清,采用生化自动分析仪测定肝功能;移植后24 h麻醉取肝脏组织,甲醛固定进行HE染色,进行病理学观察。结果FK506+HTK组ALT水平低于HTK组(P<0.05),FK506+HTK组炎性因子浸润较HTK液组减少,肝细胞结构完整;FK506+HTK组炎性因子浸润较HTK液组减少,肝细胞结构完整。结论FK506加入到灌注液中对供肝进行机械灌注,在移植后3 h内有效减少肝脏肝功能损伤和炎性损伤,对肝脏有一定的保护作用。
