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Background: Normothermic machine perfusion (NMP) has been proposed to preserve liver grafts in a less pro‐inflammatory environment. However, the effect of NMP on liver inflammation remains unclear. Therefore, we aimed at characterizing the inflammatory response during continuous NMP with a comprehensive investigation of cytokine release during perfusion. Methods: Ten porcine livers underwent either 24 h NMP or whole blood‐based NMP (WB‐NMP) immediately after procurement. WB‐NMP was used as a positive control to mimic early post‐reperfusion inflammation. High mobility group box‐1 (HMGB1), interleukin 1‐beta (IL‐1beta), tumor necrosis factor‐alpha (TNFalpha), interleukin 6 (IL‐6), 8 (IL‐8), and 10 (IL‐10), transforming growth factor‐beta (TGFbeta), aspartate transferase (AST), and hyaluronic acid were measured in the perfusate. The area under the curve (AUC) of their perfusate concentration was compared between groups. Median (IQR) is given. Results: The AUC of HMGB1 and IL‐1beta was similar between groups. Compared to WB‐NMP, NMP inhibited the release of TNFalpha [NMP: 20275 (18402–32 152), WB‐NMP: 242100 (203511–244 238); p = 0.01], IL‐6 [NMP: 1206 (338.9–1686), WB‐NMP: 8444 (7359–10 087); p = 0.03], and IL‐8 [NMP: 1635 (106.90–2130), WB‐NMP: 3951 (3090–4116); p = 0.008]. The release of TGFbeta remained unchanged but IL‐10 release was lower in NMP [1612 (1313–1916), WB‐NMP: 5591 (4312–6421); p = 0.01]. The ratios TGFbeta:TNFalpha and IL‐10:TNFalpha were significantly higher in the NMP than in the WB‐NMP group. Importantly, the AUC of AST was significantly lower during NMP [1960 (1950–2893)] than WB‐NMP [6812 (6370–7916); p = 0.02]. Conclusions: Continuous NMP leads to the release of detectable levels of cytokines with a slow, linear increase over time and a shift toward anti‐inflammatory signaling. [ABSTRACT FROM AUTHOR]

Background: Curcumin is a pleiotropic antioxidant polyphenol, which has proven to be highly protective in various models of liver injury and inflammation. We hypothesized that adding a stable aqueous curcumin formulation which comprises a water-soluble cyclodextrin curcumin formulation (CDC) complex of the water-insoluble curcumin molecule (Novobion, Espoo, Finland) to preservation solution during liver procurement may reduce ischemia-reperfusion injury and improve graft function after liver transplantation using donation after circulatory death (DCD)., Methods: In a preclinical pig model of DCD-liver transplantation, livers exposed to 15' of warm ischemia were either modulated (N = 6) with a flush of preservation solution (histidine-tryptophan-ketoglutarate) containing CDC (60 µmol/L) through the vena porta and the aorta, or not (controls, N = 6) before 4 h of cold storage. Area under the curve of log serum aspartate aminotransferase, markers of graft function (lactate, glycemia, prothrombin time, and bile production), inflammation (tumor necrosis factor-alpha), and survival were monitored., Results: Area under the curve of log serum aspartate aminotransferase were similar between curcumin and control groups (22.12 [20.87-24.88] versus 25.08 [22.1-26.55]; P = 0.28). No difference in the liver function markers were observed between groups except a lower serum lactate level 3-h post-reperfusion in the curcumin group (3 [1.95-6.07] versus 8.2 [4.85-13.45] mmol/L; P = 0.05). Serum tumor necrosis factor-alpha levels were similar in each group. Recipient survival rates were found similar., Conclusions: CDC added to the preservation solution in DCD liver pig model did not improve ischemia-reperfusion injury severity, liver function, or survival. Further efforts are needed to explore this strategy, particularly with dynamic preservation, which finds its way into clinical practice., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)