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The role of vitamin K in animal health has not received much attention. Vitamin K studies have, for the most part, addressed the use of animals in the investigation of vitamin K physiology and pathophysiology, often using the rodent as a model system. However, vitamin K performs the same role in animals as it does in man and there are areas, such as animal nutrition, where a better understanding of animal requirements in general, and with ageing, could benefit animal health and continued well‐being.

Background: Increased intracranial pressure (ICP) worsens the outcome of acute liver failure (ALF). This study investigates the underlying pathophysiological mechanisms and evaluates the therapeutic effect of albumin dialysis in ALF with use of the Molecular Adsorbents Recirculating System without hemofiltration/dialysis (modified, M-MARS). Methods: Pigs were randomized into three groups: sham, ALF, and ALF + M-MARS. ALF was induced by hepatic devascularization (time = 0). M-MARS began at time = 2 and ended with the experiment at time = 6. ICP, arterial ammonia, brain water, cerebral blood flow (CBF), and plasma inflammatory markers were measured. Results: ICP and arterial ammonia increased significantly over 6 hrs in the ALF group, in comparison with the sham group. M-MARS attenuated (did not normalize) the increased ICP in the ALF group, whereas arterial ammonia was unaltered by M-MARS. Brain water in the frontal cortex (grey matter) and in the subcortical white matter at 6 hrs was significantly higher in the ALF group than in the sham group. M-MARS prevented a rise in water content, but only in white matter. CBF and inflammatory mediators remained unchanged in all groups. Conclusion: The initial development of cerebral edema and increased ICP occurs independently of CBF changes in this non-inflammatory model of ALF. Factor(s) other than or in addition to hyperammonemia are important, however, and may be more amenable to alteration by albumin dialysis.

Background/Aims: Ammonia reduction is the target for therapy of hepatic encephalopathy (HE) but lack of quantitative data about how the individual organs handle ammonia limit our ability to develop novel therapeutic strategies. The study aims were to evaluate interorgan ammonia metabolism quantitatively in a devascularised pig model of acute liver failure (ALF). Methods: Ammonia and amino acid fluxes were measured across the portal drained viscera (PDV), kidneys, hind-leg, and lungs in ALF pigs. Results: ALF pigs developed hyperammonemia and increased glutamine levels, while glutamate levels were decreased. PDV contributed to the hyperammonemic state mainly through increased shunting and not as a result of increased glutamine breakdown. The kidneys were quantitatively as important as PDV in systemic ammonia release, while muscle took up ammonia. Data suggest that the lungs are able to remove ammonia from the circulation during the initial stage of ALF. Conclusions: Our study provides the novel observation of glutamate deficiency in a pig model of ALF. Furthermore, the kidneys are quantitatively as important as PDV in ammonia production and the muscles play an important role in ammonia removal. AD - Digestive Surgery, University Hospital Northern Norway, Norway. AU - Ytrebo LM AU - Sen S AU - Rose C AU - Ten Have GA AU - Davies NA AU - Hodges S AU - Nedredal GI AU - Romero-Gomez M AU - Williams R AU - Revhaug A AU - Jalan R AU - Deutz NE LA - ENG PT - JOURNAL ARTICLE DEP - 20060615 TA - Am J Physiol Gastrointest Liver Physiol JID - 100901227

We describe a method for the determination of the two major urinary metabolites of vitamin K as the methyl esters of their agyclone structures, 2-methyl-3-(3-3-carboxymethylpropyl)-1,4-naphthoquinone (5C-side-chain metabolite) and 2-methyl-3-(5-carboxy-3-methyl-2-pentenyl)-1,4-naphthoquinone (7C-side-chain metabolite), by HPLC with electrochemical detection (ECD) in the redox mode. Urinary salts were removed by reversed-phase (C18) solid phase extraction (SPE) and the predominately conjugated vitamin K metabolites hydrolysed with methanolic HCl. The resultant carboxylic acid aglycones were quantitatively methylated with diazomethane and fractionated by normal-phase (silica) SPE. Final analysis was by reversed-phase (C18) HPLC with a methanol-aqueous mobile phase. Metabolites were detected by amperometric, oxidative ECD of their quinol forms, which were generated by post-column coulometric reduction at an upstream electrode. The assay gave excellent linearity (r2 typically = 0.999) and high sensitivity with an on-column detection limit of