Donor age is an independent, strong prognostic factor in adult-to-adult LDLT.

No abstract

The current drastic shortage of donor organs has led to acceptance of extended-criteria donors for transplantation, despite higher risk of primary nonfunction. Here, we report the impact of subnormothermic machine perfusion (SMP) preservation on the protection of >50% macrosteatotic livers. Dietary hepatic steatosis was induced in Wistar rats via 2-day fasting and subsequent 3-day re-feeding with a fat-free, carbohydrate-rich diet. This protocol induces 50-60% macrovesicular steatosis, which should be discarded when preserved via cold storage (CS). The fatty livers were retrieved and preserved for 4 h using either CS in histidine-tryptophan-ketoglutarate or SMP in polysol solution. Graft functional integrity was evaluated via oxygenated ex vivo reperfusion for 2 h at 37°C. SMP resulted in significant reductions in not only parenchymal alanine aminotransferase (p < 0.001), but also mitochondrial glutamate dehydrogenase (p < 0.001) enzyme release. Moreover, portal venous pressure (p = 0.047), tissue adenosine triphosphate (p = 0.001), bile production (p < 0.001), high-mobility group box protein-1 (p < 0.001), lipid peroxidation, and tissue glutathione were all significantly improved by SMP. Electron microscopy revealed that SMP alleviated deleterious alterations of sinusoidal microvasculature and hepatocellular mitochondria, both of which are characteristic disadvantages associated with steatosis. SMP could protect 50-60% macrosteatotic livers from preservation/reperfusion injury, and may thus represent a new means for expanding available donor pools.

Hyaluronan (HA) has been utilized as a supplement. However, the absorption of orally administrated HA remains controversial. The degradation and absorption of HA in the intestine were investigated in this study. HA excretion into the feces, degradation in the intestinal tract, absorption through the large intestine, and translocation to the blood and skin were examined. HA administered orally was not detected in rat feces. HA was degraded by cecal content, but not by artificial gastric juice and intestinal juice. Oligosaccharide HA passed through excised large intestine sacs. Furthermore, disaccharides, tetrasaccharides, and polysaccharides HA were distributed to the skin of rats following oral administration of high molecular weight HA (300 kDa). The results of the study suggest that orally administered HA is degraded to oligosaccharides by intestinal bacteria, and oligosaccharide HA is absorbed in the large intestine and is subsequently distributed throughout the tissues, including the skin.

Preconditioning by brief ischemia protects not only the concerned organ but also other distant organs against subsequent lethal damage; this is called remote ischemic preconditioning (RIPC). This study was designed to investigate the impact of intestinal RIPC on hepatic ischemia/reperfusion injury (IRI) with a special interest in heme oxygenase 1 (HO-1) induction in the second window of protection (SWOP). Male Wistar rats were randomly assigned to 1 of 2 groups: an RIPC group or a sham group. Before hepatic IRI, either intestinal RIPC, consisting of 2 cycles of 4-minute superior mesenteric artery clamping separated by 11 minutes of declamping (RIPC group), or a sham procedure (sham group) was performed. After 48 hours of recovery, the rats were exposed to 30 minutes of total hepatic IRI. Transaminase releases and proinflammatory cytokines were determined at several time points after reperfusion. Histopathological analysis and animal survival were also investigated. Intestinal RIPC significantly lowered transaminase release (alanine aminotransferase at 2 hours: 873.3 ± 176.4 IU/L for the RIPC group versus 3378.7 ± 871.1 IU/L for the sham group, P < .001) as well as proinflammatory cytokine production (tumor necrosis factor α at 2 hours: 930 ± 42 versus 387 ± 17 pg/μL, P < .001). The morphological integrity of the liver and the ileum was maintained significantly better with intestinal RIPC; this reached statistical significance not only in Suzuki's liver injury score (3.5 ± 0.2 versus 0.7 ± 0.5, P = .007) but also in Park's score for intestinal damage (4.0 ± 0.4 versus 2.0 ± 0.2, P = .007). Animal survival was also markedly improved (83.1% versus 15.4%, P < .001). As a mechanism underlying this protection, HO-1 was substantially induced in liver tissue, especially in hepatocytes, with remarkable up-regulation of bradykinin in the portal blood, whereas HO-1 protein induction in enterocytes was not significant. In conclusion, intestinal RIPC remarkably attenuates hepatic IRI in the SWOP, presumably by HO-1 induction in hepatocytes.