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Background Due to the drastic shortage of organ donors, clinicians are increasingly considering the use of deceased after cardiac death donors (DCD). Compatible solutes like Ectoine and Hydroxyectoine are produced by extremophilic bacteria as a cell protectant to survive in harsh environments. We hypothesized that the addition of Hydroxyectoine to Histidine-Tryptophan-Ketoglutarate solution (HTK) could ameliorate cold ischemic preservation injury of DCD livers. Material and methods Rat livers were harvested from male Wistar rats weighing 250-300 g. Three experimental groups (n=5 per group) were studied: (1) CONTROLS: cold static storage in HTK for 24 h, (2) DCD: 30-min warm ischemia time and 24-h cold static storage in HTK, and (3) DCD+Hydroxyectoine: like DCD, but with 24-h cold static storage in HTK+Hydroxyectoine. Viability of the livers was assessed after 24 h of preservation by isolated perfusion for 45 min with oxygenated Krebs-Henseleit buffer solution. Results (mean ±SEM, Control vs. DCD vs. DCD+Hydroxyectoine) Parenchymal enzyme release was significantly lower in DCD+Hydroxyectoine compared to DCD (AST: 9±0.54; 56.8±2.05; 32.2±7.25 U/L, ALT: 9.5±0.5; 37.75±9.6; 17.5±4.17 U/L). Bile production at the end of 45 min reperfusion was significantly higher in DCD+Hydroxyectoine (5.16±1.32; 1.36±0.34; 10.75±2.24 µL/g liver weight/45 min). Malondialdehyde values were significantly lower in DCD+Hydroxyectoine (0.8±0.09, 1.14±0.18, 0.77±0.08 nmol/mL). Intercellular adhesion molecule-1 showed significantly lower values in DCD+Hydroxyectoine (219.07±51.79, 431.9±35.70, 205.2±37.71 pg/mL) and the portal venous pressure at 45 min was lower compared to DCD (20.41±0.12, 27.47±0.45, 22.08±0.78 mmHg). Conclusions Our data provide evidence for the beneficial role of Hydroxyectoine-modified HTK solution for the preservation of DCD livers compared to HTK.

BACKGROUND Results in small bowel transplantation are inferior compared to other solid organ transplantations, among other reasons, due to a specific vulnerability to ischemia/reperfusion injury. New strategies are needed to improve organ storage. Here we compare static cold storage in University of Wisconsin solution to storage supplemented with molecular oxygen gas insufflation. MATERIAL AND METHODS Rat small bowel was retrieved and either stored unoxygenated (UW) or oxygenated (UW+O2) for 18 h at 4°C. Biochemical parameters, mucosal function, Toll-like receptor upregulation, and parameters of structural integrity were evaluated following isolated reperfusion in vitro for 30 min at 37°C. RESULTS Oxygenation showed: ATP concentration was 82 times higher; lactate dehydrogenase release was continuously lower over 30 min; malondialdehyde, a final product of lipid peroxidation (UW+O2 vs. UW; 2.7±0.92 nmol/mL vs. 17.22±10.1 nmol/mL; P0.05) and nitric oxide concentration (0.87±0.27 µmol/L vs. 2.17±0.29 µmol/L; P0.001) were significantly lower; whereas mucosal functional integrity (galactose uptake) was better preserved (0.47±0.18 mg/dL vs. 0.35±0.05 mg/dL). Amelioration of tissue damage could be demonstrated by reduced apoptosis (3.3±1.2 AU vs. 28.4±10 AU; P0.05), and preserved subcellular integrity. Toll-like receptors were significantly less upregulated (TLR2 0.32±0.1 vs. 2.1±1.5-fold and TLR4 1.53±1.14 vs. 11.79±5.4-fold; P0.05). CONCLUSIONS Oxygenated storage is superior to standard storage in University of Wisconsin solution in terms of energetics, tissue damage, and mucosal integrity.