背景:在亚正常体温/正常体温下的体外肝脏机器灌注越来越多地应用于移植领域,以在移植前储存和评估机器上的器官。目前,各种灌注概念在临床和临床前应用。在过去的6年里,多学科团队,一种新的基于血液的灌注技术被开发出来,以保持肝脏存活和体外代谢活跃至少一周。
方法:在这份手稿中,我们展示并比较了我们在研发(R&D)过程中面临的三种情况(第1、2和3组),主要与血液灌注液中游离血红蛋白和乳酸的测定有关。从他们在肝脏活力评估(非原位)的证明价值,这两个参数也有助于长期肝脏灌注机的研发,并且支持生物医学工程过程。
结果:第1组(灌注机上的“良好”肝脏)代表了我们观察到的乳酸和游离血红蛋白的最佳肝脏清除能力。与第2组(灌注机上的“肝脏”较差)相反,对游离血红蛋白的清除能力最差。令人惊讶的是,同样对于第2组,乳酸被清除直到灌注的第一天,然后,由于肝脏质量差,检测到乳酸值上升。这两种灌注液参数化突出了器官质量/活力对灌注过程的影响。而第3组是仅利用血液回路(没有肝脏)的灌注。
结论:了解游离血红蛋白和乳酸的可行范围(上限和下限)和持续时间有助于评估器官灌注本身的质量和开发的灌注装置的成熟度。灌注液中的游离血红蛋白与溶血率有关,这表明如何优化(温和的血液处理,最大限度地减少溶血)灌注机实际上是。一般来说,乳酸清除率的降低可能是与肝脏血液供应有关的技术问题的指示,因此有助于监测灌注实验。此外,给出了比较的可能性,根据这两个参数的给定范围评估和优化开发的肝脏灌注系统。其他研究小组可以将他们的灌注液(血液)参数与本手稿中的参数进行比较/量化。提供的数据,研究结果和建议将最终支持其他研究人员开发他们自己的灌注机或根据他们的需要修改商用灌注设备。
BACKGROUND: Ex situliver machine perfusion at subnormothermic/normothermic temperature isincreasingly applied in the field of transplantation to store and evaluateorgans on the machine prior transplantation. Currently, various perfusionconcepts are in clinical and preclinical applications. Over the last 6 years ina multidisciplinary team, a novel blood based perfusion technology wasdeveloped to keep a liver alive and metabolically active outside of the bodyfor at least one week.
METHODS: Within thismanuscript, we present and compare three scenarios (Group 1, 2 and 3) we werefacing during our research and development (R&D) process, mainly linked tothe measurement of free hemoglobin and lactate in the blood based perfusate. Apartfrom their proven value in liver viability assessment (ex situ), these twoparameters are also helpful in R&D of a long-term liver perfusion machine and moreover supportive in the biomedical engineering process.
RESULTS: Group 1 (\"good\" liver on the perfusion machine) represents the best liver clearance capacity for lactate and free hemoglobin wehave observed. In contrast to Group 2 (\"poor\" liver on the perfusion machine), that has shown the worst clearance capacity for free hemoglobin. Astonishingly,also for Group 2, lactate is cleared till the first day of perfusion andafterwards, rising lactate values are detected due to the poor quality of theliver. These two perfusate parametersclearly highlight the impact of the organ quality/viability on the perfusion process. Whereas Group 3 is a perfusion utilizing a blood loop only (without a liver).
CONCLUSIONS: Knowing the feasible ranges (upper- and lower bound) and the courseover time of free hemoglobin and lactate is helpful to evaluate the quality ofthe organ perfusion itself and the maturity of the developed perfusion device. Freehemoglobin in the perfusate is linked to the rate of hemolysis that indicates how optimizing (gentle blood handling, minimizing hemolysis) the perfusion machine actually is. Generally, a reduced lactate clearancecapacity can be an indication for technical problems linked to the blood supplyof the liver and therefore helps to monitor the perfusion experiments.Moreover, the possibility is given to compare, evaluate and optimize developed liverperfusion systems based on the given ranges for these two parameters. Otherresearch groups can compare/quantify their perfusate (blood) parameters withthe ones in this manuscript. The presented data, findings and recommendations willfinally support other researchers in developing their own perfusion machine ormodifying commercially availableperfusion devices according to their needs.