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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 vivoreperfusion 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.

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 CSin histidine‐tryptophan‐ketoglutarate or SMPin polysol solution. Graft functional integrity was evaluated via oxygenated ex vivoreperfusion for 2 h at 37°C. SMPresulted 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 SMPalleviated deleterious alterations of sinusoidal microvasculature and hepatocellular mitochondria, both of which are characteristic disadvantages associated with steatosis. SMPcould protect 50–60% macrosteatotic livers from preservation/reperfusion injury, and may thus represent a new means for expanding available donor pools. Subnormothermic machine perfusion preservation successfully protects >50% of macrosteatotic rat livers from preservation/reperfusion injury by lowering oxidative stress, mitochondrial damage, and microcirculatory impairment, which are characteristic disadvantages of steatotic liver grafts.

Liver ischemia reperfusion injury (IRI) is an important problem in liver transplantation. Thrombomodulin (TM), an effective drug for disseminated intravascular coagulation, is also known to exhibit an anti‐inflammatory effect through binding to the high‐mobility group box 1 protein (HMGB‐1) known as a proinflammatory mediator. We examined the effect of recombinant human TM(rTM) on a partial warm hepatic IRImodel in wild‐type (WT)and toll‐like receptor 4 (TLR‐4) KOmice focusing on the HMGB‐1/TLR‐4 axis. As in vitroexperiments, peritoneal macrophages were stimulated with recombinant HMGB‐1 protein. The rTMshowed a protective effect on liver IRI. The rTMdiminished the downstream signals of TLR‐4 and also HMGB‐1 expression in liver cells, as well as release of HMGB‐1 from the liver. Interestingly, neither rTMtreatment in vivonor HMGB‐1 treatment in vitroshowed any effect on TLR‐4 KOmice. Parallel in vitrostudies have confirmed that rTMinterfered with the interaction between HMGB‐1 and TLR‐4. Furthermore, the recombinant N‐terminal lectin‐like domain 1 (D1) subunit of TM(rTMD1) also ameliorated liver IRIto the same extent as whole rTM. Not only rTMbut also rTMD1 might be a novel and useful medicine for liver transplantation. This is the first report clarifying that rTMameliorates inflammation such as IRIin a TLR‐4 pathway–dependent manner. Recombinant thrombomodulin suppresses high mobility group box‐1 protein expression in liver cells, as well as its release from the liver, and it ameliorates liver ischemia–reperfusion injury in a toll‐like receptor 4 pathway‐ dependent manner. See the editorial from Ke on page 7.

Liver ischemia reperfusion injury (IRI) is an important problem in liver transplantation. Thrombomodulin (TM), an effective drug for disseminated intravascular coagulation, is also known to exhibit an anti-inflammatory effect through binding to the high-mobility group box 1 protein (HMGB-1) known as a proinflammatory mediator. We examined the effect of recombinant human TM (rTM) on a partial warm hepatic IRI model in wild-type (WT) and toll-like receptor 4 (TLR-4) KO mice focusing on the HMGB-1/TLR-4 axis. As in vitroexperiments, peritoneal macrophages were stimulated with recombinant HMGB-1 protein. The rTM showed a protective effect on liver IRI. The rTM diminished the downstream signals of TLR-4 and also HMGB-1 expression in liver cells, as well as release of HMGB-1 from the liver. Interestingly, neither rTM treatment in vivonor HMGB-1 treatment in vitroshowed any effect on TLR-4 KO mice. Parallel in vitrostudies have confirmed that rTM interfered with the interaction between HMGB-1 and TLR-4. Furthermore, the recombinant N-terminal lectin-like domain 1 (D1) subunit of TM (rTMD1) also ameliorated liver IRI to the same extent as whole rTM. Not only rTM but also rTMD1 might be a novel and useful medicine for liver transplantation. This is the first report clarifying that rTM ameliorates inflammation such as IRI in a TLR-4 pathway–dependent manner.

An 8‐month‐old entire Miniature Dachshund, weighing 4.2 kg, was presented for examination following development of a cough. Ventricular septal defect had been diagnosed tentatively in its infancy on the basis of a cardiac murmur detected by auscultation and echocardiography.

A shiba inu dog with marked abdominal distension was diagnosed with cor triatriatum dexter and surgical correction was performed under extracorporeal circulation. The total duration of cardiac arrest was 11 minutes and total perfusion time was 34 minutes. The dog had an uneventful postoperative recovery. Postoperative contrast radiography of the caudal vena cava revealed normal flow into the right heart. Abdominal distension was no longer observed. Although several methods have been used to treat cor triatriatum dexter in dogs, the authors consider surgical correction under extracorporeal circulation to be a reliable approach.

The anomeric effect has been analyzed theoretically by adopting a simple model molecule, CH2ClOH. The total energy has been found at its minimum when the Cl−C−O−H dihedral angle is 66° (gauche-staggered conformation). By representing the wave function of the molecule in terms of the MOs of two fragments, we demonstrate that the oxygen p-type lone-pair orbital participates in electron donation to the C−Cl σ* orbital in a wide range of the Cl−C−O−H dihedral angle. In contrast, a hybrid of s and p atomic orbitals of the oxygen interacts with the C−Cl σ* orbital in the antiperiplanar (or anti-staggered) conformation. Electron delocalization is depressed in the anti conformation. The orbital interaction interprets consistently the shortened C−O bond and the elongated C−Cl bond in CH2ClOH in the gauche-staggered conformation. The magnitude of the stabilization due to the effect has been estimated by using the fragment interaction orbitals, supporting the significance of electron delocalization in explaining the anomeric effect. The anomeric effect in the SN2 reaction has also been studied.

The reactivity of aminoboranes has been studied theoretically. We have derived the unoccupied reactive orbitals localized on the boron pπ atomic orbital and the occupied reactive orbitals localized on the nitrogen lone-pair orbital in these compounds. The Lewis acidity of the boron center and the Lewis basicity of the nitrogen center have been estimated, by which the effect of substituents on the reactivity of aminoboranes is systematically examined. The results show that the substituent effects in aminoboranes are somewhat different from those in other boranes and amines owing to the pπ−pπ conjugation. The experimentally observed reactivity trend in [2 + 2] cycloaddition reactions has been found to be understood in terms of local characteristics of aminoboranes as a Lewis acid and as a Lewis base. This view has been suggested to be applicable to other types of reactions of aminoboranes.

The Lewis acidity of BF3, BF2Cl, BFCl2, and BCl3 in acid−base orbital interactions has been studied. We have derived the unoccupied reactive orbitals that show the maximum localization on the boron pπ atomic orbital overlapping with the lone-pair orbital of an electron donor and have evaluated the electrophilicity of the boron center in these compounds. The Lewis acidity of boron is shown to be controlled by two factors:  localizability of the unoccupied reactive orbital on the boron pπ atomic orbital and the polarizability of the boron center. The former has been shown to be similar in magnitude in these boron halide compounds. Contrary to common belief, the conjugation between the boron atom and the attached halogen atoms is not necessarily stronger in BF3 relative to others. The trend observed in experiments and in theoretical calculations for BF3, BF2Cl, BFCl2, and BCl3 is interpreted in terms of these factors.