肝移植供肝保存新途径：机械灌注

肝移植是治疗终末期肝病最有效的方法,但由于供肝短缺形势严峻,进一步发展并完善新的离体肝脏保存技术成为必然。机械灌注（MP）是一种新型的供肝保存方法,与传统的静态冷保存相比,能更好地保存离体肝脏,甚至可以挽救非标准供肝,从而进一步扩大供肝池。根据温度不同,MP可以分为低温、亚低温以及常温3种类型。目前针对肝移植的MP尚处于临床试验阶段,其主要技术参数仍需要进一步探索验证。总之,MP为解决供肝短缺提供了新思路,为了获得临床应用仍需要进一步研究,使其简化并合理优化灌注参数。     

常温机械灌注修复边缘性供肝的临床疗效：单中心报道

目的探讨常温机械灌注（normothermic machine perfusion, NMP）修复边缘性供肝的安全性和有效性。 方法2018年9月至2019年9月,使用NMP进行6例边缘性供肝体外评估和修复,供肝来自4例心死亡和2例高胆红素血症患者。记录灌注过程的灌注参数、灌注液血气分析及生化检验指标,结合供肝外观等评估边缘性供肝是否适合移植。术后随访至少3个月,记录移植后7 d内肝功能指标、生化指标、并发症发生情况等。 结果NMP期间灌注参数稳定,肝动脉灌注流量为110~334 ml/min,门静脉灌注流量为540~1 180 ml/min。灌注液pH、PO₂、PCO₂在灌注0.5 h后基本恢复正常,乳酸水平迅速下降;肝酶水平无明显升高,胆汁pH>7.5。所有供肝灌注均匀,质地柔软,均被用于移植。受者肝移植后恢复情况良好,无一例发生原发性移植肝无功能或缺血性胆道病变,至末次随访所有患者及移植物均存活。 结论本科室在临床肝移植中应用NMP技术的初步经验提示,NMP用于边缘性供肝的保存是安全、有效的。     

BMMSCs对SD大鼠DCD供肝常温机械灌注脂肪变性的影响机制研究

目的:研究铁死亡在骨髓间充质干细胞(BMMSCs)联合常温机械灌注(NMP)修复SD大鼠心脏死亡器官捐献(DCD)脂肪变性供肝中的作用。方法:提取SD大鼠BMMSCs。建立大鼠脂肪肝DCD模型。24只SD大鼠随机分为单纯脂肪肝组(Sham)、静态冷保存组(SCS)、常温机械灌注保存组(NMP)、BMMSCs联合NMP保...     

常温机械灌注保存对DCD小型猪脂肪肝供肝的影响

目的 探讨应用常温机械灌注装置保存对DCD小型猪脂肪肝的降脂及修复作用.方法 选取巴马小型猪4只,建立脂肪肝猪DCD及热缺血时间30main动物模型后,切取肝脏约5cm×5cm放入UW液冷藏保存(SCS组),余放入常温机械灌注装置中进行灌注保存(NMP组).在保存开始后2h、4h、6h分别切取肝组织进行肝匀浆质脂质含量...     

国内首例人弃肾长时间体外常温机械灌注经验探索

目的:探讨常温机械灌注（normothermic machine perfusion,NMP）对临床弃肾的长时间保存的价值及修复作用。方法:收集1例临床弃用供肾,用回收血液对其进行体外持续NMP 9 h,记录此过程中肾脏外观、灌注液前后血气和生化以及肾脏病理的动态变化。结果:NMP的第2~5小时,肾脏外观呈现粉红色,体...     

肝脏常温机械灌注的临床研究进展与应用价值探讨

本文综述了肝常温机械灌注(NMP)的相关临床研究和其作为供肝评价工具、肝损伤及治疗平台和胰岛移植研究平台的应用价值, 以期明确肝NMP系统在肝移植中的使用现状并进一步扩大肝NMP系统在其他领域应用价值, 提出其未来潜在的研究方向。     

供肝的保存

安全有效的供肝保存是肝移植成功的先决条件，保存目的是使离体缺血的肝脏保持活力，以完成运送、供受体配型及手术。肝脏是生命支持器官．移植后必须立即恢复功能，所以对保存质量要求很高。     

常温机械灌注对大鼠心脏死亡器官捐献供肝微循环保护作用的研究

目的 探讨常温机械灌注(normothermic machine perfusion,NMP)对大鼠心脏死亡器官捐献(donation after circulatory death,DCD)供肝微循环发挥的作用.方法 采用夹闭SD大鼠胸主动脉热缺血30 min获取DCD供肝;在体外建立大鼠NMP系统.根据不同的保存供...     

细胞治疗在肝脏常温机械灌注中的应用

肝移植是目前终末期肝病治疗的最佳选择[1],但器官短缺导致超过11％的患者因肝脏失代偿和死亡而失去移植机会[2].因此人们尝试使用边缘供肝、活体供肝、劈离肝或通过改善边缘供肝进行移植,从而增加可用的肝移植数量[2-3].     

常温下长时间阻断肝血供的实验研究

目的 观察常温下阻断肝血供和选择性阻断肝静脉不同时期肝脏的变化,探讨肝脏的温缺血时间。方法 常温下阻断Wistar大鼠入肝血供30min、45min及60min,观察肝细胞的形态,结构,肝血窦内皮组织的超微结构,肝酶学指标ALT、AST的改变。结果 常温下鼠肝血流阻断在45min内肝脏的改变为可逆性改变。肝脏酶学A,B,C组ALT,AST明显高于正常（P＜0．01）,A组与B组无明显差异（P＞0．05）,C组ALT,AST高于A、B组（P＜0．01）,D组正常。结论 常温下阻断Wistar大鼠入肝血供和选择性阻断肝静脉的温缺血时间可达45min,而不出现肝脏结构改变。     

Liver graft preservation methods during cold ischemia phase and normothermic machine perfusion

The growing demand for donor organs requires measures to expand donor pool.Those include extended criteria donors, such as elderly people, steatotic livers,donation after cardiac death, etc. Static cold storage to reduce metabolic requirements developed by Collins in late 1960 s is the mainstay and the golden standard for donated organ protection. Hypothermic machine perfusion provides dynamic organ preservation at 4°C with protracted infusion of metabolic substrates to the graft during the ex vivo period. It has been used instead of static cold storage or after it as short perfusion in transplant center. Normothermic machine perfusion(NMP) delivers oxygen, and nutrition at physiological temperature mimicking regular environment in order to support cellular function. This would minimize effects of ischemia/reperfusion injury.Potentially, NMP may help to estimate graft functionality before implantation into a recipient. Clinical studies demonstrated at least its non-inferiority or better outcomes vs static cold storage. Regular grafts donated after brain death could be safely preserved with convenient static cold storage. Except for prolonged ischemia time where hypothermic machine perfusion started in transplant center could be estimated to provide possible positive reconditioning effect. Use of hypothermic machine perfusion in regular donation instead of static cold storage or in extended criteria donors requires further investigation. Multicenter randomized clinical trial supposed to be completed in December 2021. Extended criteria donors need additional measures for graft storage and assessment until its implantation. NMP is actively evaluating promising method for this purpose.Future studies are necessary for precise estimation and confirmation to issue clinical practice recommendations.     

肾脏常温机械灌注与无缺血肾移植

为了增加扩大标准供者(ECD)肾脏的利用率,肾脏保存方法近年来在不断发展。常温机械灌注(NMP)的使用,促进了离体供肾保存、评估和修复,以及肾移植手术方式革新。中山大学附属第一医院器官移植中心首创的无缺血肾移植(IFKT)手术,利用肾脏NMP机器在供肾获取、保存、移植全过程中,保持供肾血流和供氧不中断,从根本上避免了供肾缺血-再灌注损伤(IRI),降低了术后移植物功能延迟恢复(DGF)和急性排斥反应发生的风险。本文着重总结肾脏NMP的新进展,以及IFKT手术方式和近期疗效,旨在为提高ECD供肾利用率、解决器官短缺的问题提供参考。     

供肝短缺形势下的我国肝移植策略

近5年来我国肝移植发展非常迅速,然而,供肝短缺成为制约临床肝移植发展的瓶颈。因此,拓展供肝来源成为目前肝移植临床的重点。活体肝移植在尸体供肝受限的情况下可以很好地扩展供肝来源,且活体供肝具有活力强、冷缺血时间短等优势;劈裂式肝移植可增加15％～28％的供肝数量,有望成为解决供肝短缺的主要手术方式之一;脑死亡供者在西方国家是移植器官的主要来源,在我国亦有广大的应用前景,但脑死亡供者器官移植刚刚起步,有许多问题亟待研究;此外,边缘供肝,包括脂肪变性肝脏、HBsAg阳性肝脏、超过60岁的高龄供者捐献的肝脏、冷缺血时间超过14h的盱脏等均可用以缓解日益突出的供肝短缺矛盾。     

Hypothermic reconditioning after cold storage improves postischemic graft function in isolated porcine kidneys

Delayed graft function still represents a major complication in clinical kidney transplantation. Here we tested the possibility to improve functional outcome of cold stored kidneys a posteriori by short‐term hypothermic machine perfusion immediately prior to reperfusion. A total of 18 kidneys from female German Landrace pigs was flushed with Histidine‐Tryptophan‐Ketoglutarate solution and cold‐stored for 18 h (control). Some grafts were subsequently subjected to 90 min of hypothermic reconditioning by hypothermic machine perfusion with (HR+O₂) or without (HR?O₂) oxygenation of the perfusate. Early graft function of all kidneys was assessed thereafter by warm reperfusion in vitro (n = 6, respectively). Renal function upon reperfusion was significantly enhanced by HR+O₂ with more than threefold increase in renal clearances of creatinine and urea. HR+O₂ also led to significantly higher urinary flow rates and abrogated the activation of caspase 3. By contrast, HR?O₂ was far less effective and only resulted in minor differences compared to control. It is derived from the present data that initial graft function can be significantly improved by 2 h of oxygenated machine perfusion after arrival of the preserved organ in the transplantation clinic.     

Impact of machine perfusion after long static cold storage on delayed graft function incidence and duration and time to hospital discharge

Delayed graft function (DGF) is very high in our center (70%‐80%), and we usually receive a kidney for transplant after more than 22 hours of static cold ischemia time (CIT). Also, there is an inadequate care of the donors, contributing to a high rate of DGF. We decided to test whether machine perfusion (MP) after a CIT improved the outcome of our transplant patients. We analyzed the incidence of DGF, its duration, and the length of hospital stay (LOS) in patients who received a kidney preserved with MP after a CIT (hybrid perfusion—HP). We included 54 deceased donors kidneys preserved with HP transplanted from Feb/13 to Jul/14, and compared them to 101 kidney transplants preserved by static cold storage (CS) from Nov/08 to May/12. The median pumping time was 11 hours. DGF incidence was 61.1% vs 79.2% (P = .02), median DGF duration was 5 vs 11 days (P < .001), and median LOS was 13 vs 18 days (P < .011), for the HP compared to CS group. The observed reduction of DGF with machine perfusion did not occur in donors over 50 years old. In the multivariate analysis, risk factors for DGF, adjusted for CIT, were donor age (OR, 1.04; P = .005) and the absence of use of MP (OR, 1.54; P = .051). In conclusion, the use of HP contributed to faster recovery of renal function and to a shorter length of hospital stay.