Conventional static cold storage (SCS) exacerbates ischemic injury in the DCD liver, leading to severe complications for transplant recipients. To address this issue, clinical application of MP technology for donor liver preservation is underway. Simultaneously, efforts are focused on the development of various MP instruments, validated through relevant animal model experiments. Effective large animal trials play a pivotal role in clinical applications. However, challenges persist in the ex vivo preservation of DCD livers and the transplantation procedure in pigs. These hurdles encompass addressing the prolonged preservation of donor livers, conducting viability tests, alleviating ischemic injuries, and shortening the anhepatic phase. The use of a variable temperature-controlled MP device facilitates the prolonged preservation of DCD livers through sequential Dual Hypothermic Oxygenated Machine Perfusion (DHOPE) and Normothermic Machine Perfusion (NMP) modes. This protocol enhances the porcine OLTx model by improving the quality of DCD livers, optimizing the anastomosis technique, and reducing the duration of the anhepatic phase.

目的 比较不同供体来源的同种异体血管在长时间深低温保存后出现的病理学差异.方法 将深低温保存时间超过3年的同种异体髂动脉分为脑死亡器官捐献(donation after brain death,DBD)组和心死亡器官捐献(donation after circulatory death,DCD)组,每组随机选取10例,复温后取样,通过苏木精-伊红(hematoxylin and eosin,HE)染色以及Masson染色观察血管的病理特点.结果 与DBD组对比,DCD组供体经历的热缺血时间较长(P＜0.01).经过长时间深低温保存后,DCD组血管在HE染色下的血管中膜损伤评分、外膜损伤评分和总体损伤评分高于DBD组(P＜0.05),其中血管外膜和中膜损伤评分与热缺血时间呈正相关.在Masson染色下,DCD组血管胶原纤维光密度值低于DBD组(P＜0.05),且该值与热缺血时间呈负相关.结论 DBD供体来源的同种异体髂动脉超3年深低温保存的质量优于DCD供体来源血管.

随着器官捐献数量不断增加和扩大标准供者(ECD)供肝定义不断拓展,供肝质量必然成为影响肝移植高质量发展的突出问题,也是相关领域的研究重点.最大限度解决器官短缺和推动器官移植高质量发展是我国器官捐献与移植事业发展的方向.近年来,利用机械灌注(MP)对供肝进行灌注、保存、评估及修复,已成为当前国际上提高肝移植质量的研究热点.本文针对国内外ECD供肝的不同应用情况,结合国际上MP研究进展和本中心有关研究经验,探讨整合器官保护技术建设器官重症监护室(ICU)的可行性,拟在推动我国器官移植高质量发展同时,进一步丰富器官捐献与移植"中国模式"的技术内涵.

There is a dearth of effective parameters for selecting potentially transplantable liver grafts from expanded-criteria donors. In this study, we used a nuclear magnetic resonance (NMR) relaxation analyzer-based assay to assess the viability of ex vivo livers obtained via porcine donation after circulatory death (DCD). Ex situ normothermic machine perfusion (NMP) was utilized as a platform for viability test of porcine DCD donor livers. A liver-targeted contrast agent, gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA), was injected into the perfusate during NMP, and the dynamic biliary excretion of the Gd-EOB-DTPA was monitored by measuring the longitudinal relaxation time (T1). The longitudinal relaxation rate (R1) of the bile was served as a parameter. The delay of increase in biliary R1 during early stage of NMP indicated the impaired function of liver grafts in both warm and cold ischemia injury, which was correlated with the change of alanine aminotransferase. The preservative superiority in cold ischemia of dual hypothermic oxygenated machine perfusion could also be verified by assessing biliary R1 and other biochemical parameters. This study allows for the dynamic assessment of the viability of porcine DCD donor livers by combined usage of ex situ NMP and NMR relaxation time based assay, which lays a foundation for further clinical application.

肝移植是治疗终末期肝病唯一有效的方法,然而供肝短缺严重制约了临床上的应用.为了解决供肝短缺问题,以往认为风险较大的心脏死亡器官捐献(donation after cardiac death,DCD)供肝,越来越多地用于临床移植[1-3].DCD在心脏停跳过程中不可避免要经历低血压、休克、缺氧等热缺血时间(warm ischemia time,WIT)[4],WIT过长会影响供肝质量,降低供肝利用率,增加移植肝功能延迟恢复、缺血性胆病(ischemic cholangiopathy,IC)等并发症发生率[5-6],严重者甚至出现原发性移植物无功能(primary graft nonfunction,PNF)[7].有报道称DCD供肝移植术后上述并发症发生率可高达50%[8],随着评估和应用经验增加,DCD肝移植疗效有了明显的改善,但仍是影响DCD肝移植预后的主要问题[9-10].

Objective: To investigate the clinical evaluation effects of Corona Virus Disease 2019 (COVID-19) risk assessment scale on preoperative and surgical risk of liver transplantation during the COVID-19 outbreak

目的 探讨在体常温局部灌注对猪心脏死亡器官捐献(donation after cardiac death,DCD)肝脏的修复作用.方法 45 kg巴马小型猪(n=3)在麻醉后,分别经颈静脉、髂动脉插入导管并与体外膜肺氧合(extracorporeal membrane oxygenation,ECMO)连接.静脉注射氯化钾溶液引发心跳骤停,30 min后置入球囊导管阻断胸主动脉,开始运转设备进行在体常温(37℃)局部灌注4 h,静脉血氧维持在60%～70%,每隔1 h检测其血气、生化指标,灌注前、后取肝脏组织,进行病理观察.结果 4 h灌注过程中,设备运转稳定,乳酸显著下降(P<0.05),肝脏持续有胆汁生成,丙氨酸转氨酶、谷氨酰转肽酶及总胆红素浓度变化无统计学差异(P>0.05),天冬氨酸转氨酶在正常范围内,病理切片提示灌注前、后的病理评分差异极其显著(P<0.01).结论 本研究证明在体常温局部灌注对猪DCD30 min肝脏具有修复作用.

目的 探讨便携式在体机械灌注设备(IMPD)运行稳定性和保护无心跳大动物供器官的作用.方法 6只健康清洁巴马小型猪麻醉后开腹,分别经腹主动脉、下腔静脉插管并连接到自主研发的便携式IMPD,静脉注射氯化钾骤停心脏,观察5 min无复跳,启动设备对动物器官进行常温(37℃)机械灌注.调整离心泵转速和灌注流量以控制静脉血氧饱和度维持在60％ ～70％,持续灌注12 h,每2小时为观察时间点,记录设备管路流量、离心泵转速和流量/转速比值,检测肝、肾功能和血液内环境指标,灌注结束后获取胆总管、肝、肾和小肠组织,HE染色后光镜下评估病理改变情况.采用重复测量资料单因素方差分析比较灌注过程中各时间点运行参数、肝肾功能和血液内环境指标,组内两两比较采用LSD法,P<0.05为差异有统计学意义.结果 全部实验均完成12 h灌注,灌注过程中设备运行稳定,无故障或停机意外,管路流量、离心泵转速和流量/转速比值均稳定.ALT、总胆红素(TBIL)和谷氨酰转移酶(GGT)稳定,灌注开始至结束各时间点与术前相比,差异均无统计学意义(P均>0.05).灌注开始后AST缓慢上升,灌注第8、10和12小时AST分别为(73±21)、(90±30)和(114±48)(U/L),与术前相比,差异均有统计学意义(P均<0.05).在实验猪心脏停跳的5 min内,乳酸在灌注开始时便处于峰值,自灌注第8小时起,乳酸数值与峰值相比差异均有统计学意义(P均<0.05).K+浓度水平自灌注第2小时起各时间点与灌注开始时相比,差异均有统计学意义(P均<0.05).ALT、TBIL、GGT、血尿素氮、血清肌酐、血气分析指标、Na+、Ca2+和Cl-浓度水平稳定,灌注开始至结束各时间点数值与灌注开始时相比,差异均无统计学意义(P均>0.05).自灌注开始后持续有胆汁生成、尿量产生.供肝灌注12 h的过程中,肝脏始终保持外观红润、质地柔软、边缘锐利.灌注结束后,胆总管、肝、肾和小肠组织病理结果 示组织结构完整,无淤血和大面积坏死征象.结论 便携式IMPD可以稳定灌注无心跳猪供器官12 h,可以较好维护胆总管、肝、肾和小肠器官.

机械灌注(MP)技术是器官移植领域的全球研究热点之一,近年的探索成果显示出其在器官保存、器官活力评估、修复受损器官中的优异性,将引领器官捐献与移植模式的变革.本文就近期MP技术在提升器官保存效果、评估器官活力、修复器官以及进行干预性治疗等方面的研究进展进行综述,并讨论未来临床应用的潜在模式.