LAUSR

Ex situ liver machine perfusion at subnormothermic/normothermic temperature is increasingly applied in the field of transplantation to store and evaluate organs on the machine prior transplantation. Currently, various perfusion concepts are in clinical and preclinical applications. Over the last 6 years in a multidisciplinary team, a novel blood based perfusion technology was developed to keep a liver alive and metabolically active outside of the body for at least one week. Within this manuscript, we present and compare three scenarios we were facing during our research and development (R&D) process, mainly linked to the measurement of free hemoglobin and lactate in the blood based perfusate. Apart from their proven value in liver viability assessment (ex situ), these two parameters are also helpful in R&D of a long-term liver perfusion machine and moreover supportive in the biomedical engineering process. Group 1 ("good" liver on the perfusion machine) represents the best liver clearance capacity for lactate and free hemoglobin we have 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 and afterwards, rising lactate values are detected due to the poor quality of the liver. These two perfusate parameters clearly 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). Knowing the feasible ranges (upper- and lower bound) and the course over time of free hemoglobin and lactate is helpful to evaluate the quality of the organ perfusion itself and the maturity of the developed perfusion device. Free hemoglobin in the perfusate is linked to the rate of hemolysis that indicates how optimized (gentle blood handling, minimizing hemolysis) the perfusion machine actually is. Generally, a reduced lactate clearance capacity can be an indication for technical problems linked to the blood supply of the liver and therefore helps to monitor the perfusion experiments. Moreover, the possibility is given to compare, evaluate and optimize developed liver perfusion systems based on the given ranges for these two parameters. Other research groups can compare/quantify their perfusate (blood) parameters with the ones in this manuscript. The presented data, findings and recommendations will finally support other researchers in developing their own perfusion machine or modifying commercially available perfusion devices according to their needs.