Adding the oxygen carrier M101 to a cold-storage solution could be an alternative to HOPE for liver graft preservation.

BACKGROUND & AIMS: Hypothermic oxygenated machine perfusion (HOPE) is a promising technique for providing oxygen to the liver during graft preservation; however, because of associated logistical constraints, addition of an oxygen transporter to static cold-storage solutions (SCS) might be easier. M101 is marine worm haemoglobin that has been shown to improve kidney preservation in the clinic when added to SCS. This study evaluated the effects of the addition of M101 to SCS on the quality of pig liver graft preservation. METHODS: Pig liver grafts were preserved using SCS, HOPE, or SCS+M101, and the liver functions were compared during cold preservation and after orthotopic allotransplantation (OLT) in pigs. RESULTS: During preservation of the liver grafts, mitochondrial function, ATP synthesis, antioxidant capacities, and hepatocyte architecture were better preserved, and free radical production, antioxidant activities, and inflammatory mediators were lower, with HOPE or SCS+M101 than with SCS alone. However, after 1 h of preservation, liver functions with HOPE were superior to those with SCS+M101. After 6 h of preservation and OLT, blood levels of aspartate and alanine aminotransferases and lactate dehydrogenase increased with a peak effect at Day 1 post-transplant; values were similar with HOPE and SCS+M101, and were significantly lower than those in the SCS group. At Days 1 and 3, tumor necrosis factor α levels remained lower with HOPE and SCS+M101 vs. SCS. At Day 7, liver cell necrosis and inflammation were less marked in both oxygenated groups. CONCLUSIONS: When added to SCS, M101 effectively oxygenates liver grafts during preservation, preventing post-transplant injury; although graft performances are below those achieved with HOPE. LAY SUMMARY: When transported between donors and recipients, even cold-stored liver grafts need oxygen to maintain their viability. To provide them with oxygen, we added a marine worm super haemoglobin (M101) to the cold-storage solution UWCS. Using a pig liver transplant model, we revealed that livers cold stored with UWCS+M101 showed improved oxygenation compared with simple cold-storage solutions, but did not reach the oxygenation level achieved with machine perfusion.

fMRI-Based Brain Responses to Quinine and Sucrose Gustatory Stimulation for Nutrition Research in the Minipig Model: A Proof-of-Concept Study.

The minipig model is of high interest for brain research in nutrition and associated pathologies considering the similarities to human nutritional physiology, brain structures, and functions. In the context of a gustatory stimulation paradigm, fMRI can provide crucial information about the sensory, cognitive, and hedonic integration of exteroceptive stimuli in healthy and pathological nutritional conditions. Our aims were (i) to validate the experimental setup, i.e., fMRI acquisition and SPM-based statistical analysis, with a visual stimulation; (ii) to implement the fMRI procedure in order to map the brain responses to different gustatory stimulations, i.e., sucrose (5%) and quinine (10 mM), and (ii) to investigate the differential effects of potentially aversive (quinine) and appetitive/pleasant (sucrose) oral stimulation on brain responses, especially in the limbic and reward circuits. Six Yucatan minipigs were imaged on an Avanto 1.5-T MRI under isoflurane anesthesia and mechanical ventilation. BOLD signal was recorded during visual or gustatory (artificial saliva, sucrose, or quinine) stimulation with a block paradigm. With the visual stimulation, brain responses were detected in the visual cortex, thus validating our experimental and statistical setup. Quinine and sucrose stimulation promoted different cerebral activation patterns that were concordant, to some extent, to results from human studies. The insular cortex (i.e., gustatory cortex) was activated with both sucrose and quinine, but other regions were specifically activated by one or the other stimulation. Gustatory stimulation combined with fMRI analysis in large animals such as minipigs is a promising approach to investigate the integration of gustatory stimulation in healthy or pathological conditions such as obesity, eating disorders, or dysgeusia. To date, this is the first intent to describe gustatory stimulation in minipigs using fMRI.

Effects of chronic abdominal vagal stimulation of small-diameter neurons on brain metabolism and food intake.

BACKGROUND: Abdominal bilateral vagal stimulation reduces food intake in animals. However, the classical square wave, mA range current generator is poorly effective to evoke action potentials on A∂ and C neurons that represent the majority of vagal neurons at the abdominal level. OBJECTIVE/HYPOTHESIS: METHODS: The current thresholds for pulsons (S2 & S3) and millisecond pulses (S1) required to trigger action potentials were calculated in 5 anaesthetized pigs using single fibre recording. Similar stimulation protocols were compared chronically to sham stimulation in 24 pigs. After two weeks of chronic stimulation, food intake and brain metabolism were investigated. The electrical characteristics and histology of the vagus nerve were also studied. RESULTS: S3 stimulation required a lower amount of charges to trigger an action potential. Chronically applied S2 & S3 activated the dorsal vagal complex and increased the metabolism of its afferent cortical structures. They also reduced energy intake together with a reduced ingestion of high fat and high sugar diets. All these effects were not observed for the S1 group. The vagal histology for the S1, S2 and S3 groups was not different from that of the sham. CONCLUSIONS: These findings demonstrate that pulsons applied bilaterally on the abdominal vagus reduced food intake as a consequence of the activation of the brainstem and higher-order brain areas.

Defatted bovine colostrum-supplemented diet around weaning improves exocrine pancreatic secretion by means of volume, digestive enzymes, and antibacterial activity.

OBJECTIVES: Exocrine pancreatic secretion contributes to limit pathogenic bacteria-associated diarrhea. Bovine colostrum, used in the treatment of diarrhea, reduces symptoms originating from gut pathogenic bacteria overgrowth. We hypothesized that bovine colostrum may stimulate the exocrine pancreatic secretion. METHODS: Eighteen piglets fitted with 2 permanent catheters (for pancreatic juice collection and reintroduction) were allocated to 1 of the following 2 dietary treatments for 5 days: a control diet or a diet supplemented with defatted bovine colostrum. Pancreatic juice was collected daily, and digestive enzyme activities and antibacterial activity were determined. RESULTS: The prandial pancreatic juice outflow, the basal and prandial lipase output, and the basal secretion of the antibacterial activity were, respectively, 60% (P = 0.08), 154% (P = 0.08), 92% (P = 0.06), and 72% (P < 0.05) higher in piglets fed a diet supplemented with defatted bovine colostrum. CONCLUSIONS: With defatted bovine colostrum, the increased antibacterial activity secretion against Escherichia coli may limit pathogenic bacteria overgrowth of the gut and reduce diarrheal episodes. The role of secretin in the increased pancreatic juice flow and lipase secretion was considered.

Diet-related adaptation of the small intestine at weaning in pigs is functional rather than structural.

BACKGROUND: Incidence of diarrhea at weaning in commercial pigs is an important problem, and diet is thought to be a predisposing factor. The aim of this study was to determine the impact of switching from milk-based to cereal-based diets on the morphology and function of the small intestine of piglets using a model of delayed weaning to isolate the influence of the diet from that of environmental and social factors. METHODS: Forty-five piglets received a milk-based diet for 5 weeks after weaning. Thirty piglets were then switched from milk-based to wheat- or barley-based diets, mimicking the dietary change that occurs at weaning. The last 15 piglets remained on the milk-based diet. Piglets were killed 4 days after the dietary switch. Jejunal mucosa morphometry and enzyme activities were measured. Ussing chambers were used to measure intestinal permeability to macromolecules, basal electrical properties, glucose absorption, and induced chloride-secretion. RESULTS: Alkaline phosphatase- and sucrase-specific activities were higher in both groups of cereal-fed piglets than in milk-fed piglets. Dipeptidylpeptidase IV activity was higher in wheat-fed piglets than in the other groups. Na + -dependent glucose absorption was 1.7-fold higher in cereals-fed piglets than in milk-fed piglets. Serotonin-induced and vasoactive intestinal polypeptide-induced chloride secretion was doubled in cereals-fed piglets. Dietary transition did not influence the other parameters. CONCLUSIONS: These results indicate that switching from milk to cereals increased some mucosal enzyme activities, intestinal Na + -dependent glucose absorption, and response to secretagogues. This supports the hypothesis that dietary factors could initiate diarrhea in the presence of other aggravating factors, such as pathogens or environmental stress.