Two Compartment Evaluation of Liver Grafts During Acellular Room Temperature Machine Perfusion (acRTMP) in a Rat Liver Transplant Model.
Two Compartment Evaluation of Liver Grafts During Acellular Room Temperature Machine Perfusion (acRTMP) in a Rat Liver Transplant Model.
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DOI：
10.3389/fmed.2022.804834
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发表时间：
2022
影响因子：
3.9
通讯作者：
Barbas AS
中科院分区：
文献类型：
--
作者：
Abraham N;Zhang M;Cray P;Gao Q;Samy KP;Neill R;Cywinska G;Migaly J;Kahan R;Pontula A;Halpern SE;Rush C;Penaflor J;Kesseli SJ;Krischak M;Song M;Hartwig MG;Pollara JJ;Barbas AS
与常温和低温方法相比，亚常温机器灌注(SNMP)目前在临床上的发展较少，但可能有后勤上的优势。在中等温度下，移植物的需氧量低到足以满足无细胞灌流液的要求，从而消除了对携氧分子的需求。然而，这种中间代谢率足以支持胆汁的产生，胆汁正在成为移植物损伤和存活的重要指标。在这项研究中，我们假设在检测移植物损伤时，胆管间隔比灌流液更敏感。为了在大鼠模型中验证这一假设，我们用DCD进行了肝移植，并在无细胞室温机器灌流(AcRTMP)或静态冷藏(SCS)后1h控制移植肝。在机器灌流1h后，对胆汁和灌流液样本进行护理点肝功能测试。移植后24小时处死大鼠，评估移植后的功能和组织学。在acRTMP期间，所有的临床点肝功能测试都明显更集中在胆管间室，而不是灌流液间室。肝细胞损伤指标(AST、ALT)在胆管室明显升高，而在灌流液中无明显变化，可将DCD肝移植与对照肝区分开来。经典的胆管细胞损伤标志物，如γ-谷氨酸淀粉转移酶(GGT)、淀粉酶(AML)和碱性磷酸酶(AML)在胆管间室可检测到，但在灌流液间室不能检测到。与SCS相比，AcRTMP保存移植物在DCD肝移植中产生了显著的存活益处(75vs.0%，p<；0.0030)。综上所述，这些发现表明，在acRTMP期间，胆管室可能比灌流液室更敏感地反映移植物损伤。此外，在大鼠DCD肝移植中，acRTMP提供了比SCS更好的移植物保存。
Subnormothermic machine perfusion (SNMP) of liver grafts is currently less clinically developed than normothermic and hypothermic approaches, but may have logistical advantages. At intermediate temperatures, the oxygen demand of the graft is low enough to be satisfied with an acellular perfusate, obviating the need for oxygen carrying molecules. This intermediate metabolic rate, however, is sufficient to support the production of bile, which is emerging as an important indicator of graft injury and viability. In this study, we hypothesized that the biliary compartment would be more sensitive than perfusate in detecting graft injury during SNMP. To test this hypothesis in a rat model, we performed liver transplants with DCD and control liver grafts after 1 h of acellular room temperature machine perfusion (acRTMP) or static cold storage (SCS). Point of care liver function tests were measured in biliary and perfusate samples after 1 h of machine perfusion. Following transplantation, rats were sacrificed at 24 h for assessment of post-transplant graft function and histology. All point-of-care liver function tests were significantly more concentrated in the biliary compartment than the perfusate compartment during acRTMP. DCD liver grafts could be distinguished from control liver grafts by significantly higher markers of hepatocyte injury (AST, ALT) in the biliary compartment, but not in the perfusate compartment. Classical markers of cholangiocyte injury, such as gammy-glut amyl transferase (GGT), amylase (AML), and alkaline phosphatase were detectable in the biliary compartment, but not in the perfusate compartment. In comparison to SCS, graft preservation by acRTMP produced a significant survival benefit in DCD liver transplantation (75 vs. 0%, p < 0.0030). Together, these findings demonstrate that during acRTMP, the biliary compartment may be a more sensitive indicator of graft injury than the perfusate compartment. Moreover, acRTMP provides superior graft preservation to SCS in rat DCD liver transplantation.
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影响因子：
6.2
作者：
Watson CJE;Kosmoliaptsis V;Randle LV;Gimson AE;Brais R;Klinck JR;Hamed M;Tsyben A;Butler AJ
通讯作者：
Butler AJ
影响因子：
25.7
作者：
Dutkowski, Philipp;Schlegel, Andrea;Clavien, Pierre-Alain
通讯作者：
Clavien, Pierre-Alain
DOI：
10.1111/ajt.12727
发表时间：
2014-06
期刊：
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子：
--
作者：
Bruinsma BG;Yeh H;Ozer S;Martins PN;Farmer A;Wu W;Saeidi N;Op den Dries S;Berendsen TA;Smith RN;Markmann JF;Porte RJ;Yarmush ML;Uygun K;Izamis ML
通讯作者：
Izamis ML
影响因子：
8.8
作者：
Watson, Christopher J. E.;Kosmoliaptsis, Vasilis;Butler, Andrew J.
通讯作者：
Butler, Andrew J.
影响因子：
0.9
作者：
Gringeri, E.;Bonsignore, P.;Cillo, U.
通讯作者：
Cillo, U.