Ultrastructure of the hemomicrocirculatory bed and parenchymatous-stromal elements of the pancreas and liver in a model of acute pancreatitis using different doses of L-arginin

Background. The development of acute pancreatitis is not limited to isolated damage to the pancreas. After creating models of acute pancreatitis using various substances that enhance the secretion of the gland, have a toxic or local activating effect, the researchers showed their dose-dependent effect. The question of the reaction of the hepatic microcirculation system during the development of acute pancreatitis, as well as their pathogenetic significance in the development of pathomorphological changes in the pancreas and liver in most aspects remains open. Objective. The purpose of the current study was to define the role of the hepatic mircocirculation in development of ultrastructural parenchymatous-stromal changes of the pancreas and liver in a model of acute pancreatitis using different doses of L-arginin. Methods. The variants of acute pancreatitis model were used with injection of L-arginin in dosage 3 g/kg; 4 g/kg and 5 g/kg. The morphological research of pancreas and liver were carried out in 1, 4, 8, 12, 24, 48 and 72 hours after initiation of inflammation. Results. The visible reaction of hepatic mircocirculation in the experimental model of acute pancreatitis was depended on character of pathomorphological changes in pancreas. This reaction demonstrated the phase character including: 1) activation of hepatic circulation, first of all in portal component, against a background of pancreatic enzyme toxemia; 2) development of inflammatory, dystrophic, destructive and necrotic changes in hepatic parenchyme together with mircocirculation disorders against a background of pancreatic necrotic toxemia; 3) recovery and adaptation or decompensation processes in mircocirculation system of liver and hepatic parenchyme depending on the degree of pancreatogenic toxemia|. Conclusion. Within 72 hours of the experiment, at the lowest and middling doses of L-arginin, in the context of reduction of acute pancreatitis, there is a gradual renovation of the structure of the microvessels and normalization of the microcirculation of the liver. In the maximum doses L-arginin cause degradation of the liver microvessels with the progression of hemorrhages, slit red blood cells and platelet aggregation, which causes blockage of the microcirculation and the development of necrotic changes in the hepatic parenchyma.

Increased Hepatic Microvascular Density, Oxygenation, and VEGF in the Hypertrophic Lobe following Portal Vein Embolization in Rabbits

<b><i>Introduction:</i></b> The microvascular events following portal vein embolization (PVE) are poorly understood despite the pivotal role of the microcirculation in liver regeneration and tumor progression. We aimed to assess the changes in hepatic microvascular perfusion and neo-angiogenesis after experimental PVE. <b><i>Methods:</i></b> PVE of the cranial liver lobes was performed in 12 New Zealand White rabbits divided into 2 groups of permanent (P-PVE) and reversible PVE (R-PVE), respectively. Hepatobiliary scintigraphy and CT were used to evaluate hepatic function and volume. Hepatic microcirculation was assessed using a handheld vital microscope (Cytocam) to measure microvascular density (total vessel density; TVD) before PVE, right after PVE, and 20 min after PVE, as well as at 14 days (D14 post-PVE) and 35 days (D35 post-PVE). Additionally, on D35, microvascular PO₂ and liver parenchymal VEGF were assessed. <b><i>Results:</i></b> Eleven rabbits were included after PVE (R-PVE, <i>n</i> = 5; P-PVE, <i>n</i> = 6). TVD in the nonembo­lized (hypertrophic) lobes was higher than in the embolized (atrophic) lobes of the P-PVE group at D35 post-PVE (36.7 ± 7.2 vs. 23.4 ± 4.9 mm/mm²; <i>p</i> &#x3c; 0.05). In the R-PVE group, TVD in the nonembolized lobes was not increased at D35. Function and volume were increased in the nonembolized lobes of the P-PVE group compared to the embolized lobes, but not in the R-PVE group. Likewise, the mmicrovascular PO₂ and VEGF staining rate were higher in the nonembolized lobes of the P-PVE group at D35 post-PVE. <b><i>Discussion/Conclusion:</i></b> Successful volumetric and functional hypertrophy of the nonembolized lobe was accompanied by microvascular alterations featuring increased neo-angiogenesis, microvascular density, and microvascular oxygen pressure following P-PVE.

Sodium Thiosulfate Improves Intestinal and Hepatic Microcirculation Without Affecting Mitochondrial Function in Experimental Sepsis

IntroductionIn the immunology of sepsis microcirculatory and mitochondrial dysfunction in the gastrointestinal system are important contributors to mortality. Hydrogen sulfide (H2S) optimizes gastrointestinal oxygen supply and mitochondrial respiration predominantly via K(ATP)-channels. Therefore, we tested the hypothesis that sodium thiosulfate (STS), an inducer of endogenous H2S, improves intestinal and hepatic microcirculation and mitochondrial function via K(ATP)-channels in sepsis.MethodsIn 40 male Wistar rats colon ascendens stent peritonitis (CASP) surgery was performed to establish sepsis. Animals were randomized into 4 groups (1: STS 1 g • kg-1 i.p., 2: glibenclamide (GL) 5 mg • kg-1 i.p., 3: STS + GL, 4: vehicle (VE) i.p.). Treatment was given directly after CASP-surgery and 24 hours later. Microcirculatory oxygenation (µHBO2) and flow (µflow) of the colon and the liver were continuously recorded over 90 min using tissue reflectance spectrophotometry. Mitochondrial oxygen consumption in tissue homogenates was determined with respirometry. Statistic: two-way ANOVA + Dunnett´s and Tukey post - hoc test (microcirculation) and Kruskal-Wallis test + Dunn’s multiple comparison test (mitochondria). p &lt; 0.05 was considered significant.ResultsSTS increased µHbO2 (colon: 90 min: + 10.4 ± 18.3%; liver: 90 min: + 5.8 ± 9.1%; p &lt; 0.05 vs. baseline). Furthermore, STS ameliorated µflow (colon: 60 min: + 51.9 ± 71.1 aU; liver: 90 min: + 22.5 ± 20.0 aU; p &lt; 0.05 vs. baseline). In both organs, µHbO2 and µflow were significantly higher after STS compared to VE. The combination of STS and GL increased colonic µHbO2 and µflow (µHbO2 90 min: + 8.7 ± 11.5%; µflow: 90 min: + 41.8 ± 63.3 aU; p &lt; 0.05 vs. baseline), with significantly higher values compared to VE. Liver µHbO2 and µflow did not change after STS and GL. GL alone did not change colonic or hepatic µHbO2 or µflow. Mitochondrial oxygen consumption and macrohemodynamic remained unaltered.ConclusionThe beneficial effect of STS on intestinal and hepatic microcirculatory oxygenation in sepsis seems to be mediated by an increased microcirculatory perfusion and not by mitochondrial respiratory or macrohemodynamic changes. Furthermore, the effect of STS on hepatic but not on intestinal microcirculation seems to be K(ATP)-channel-dependent.

Hepatoprotection by L-Ornithine L-Aspartate in Non-Alcoholic Fatty Liver Disease

Background.Non-alcoholic fatty liver disease (NAFLD) is the leading chronic hepatic condition worldwide and new approaches to management and treatment are limited.Summary.L-ornithine L-aspartate (LOLA) has hepatoprotective properties in patients with fatty liver of diverse etiology and results of a multicenter randomized clinical trial reveal that 12 weeks treatment with oral LOLA (6–9 g/d) results in a dose-related reduction in activities of liver enzymes and triglycerides together with significant improvements of liver/spleen CT ratios. A preliminary report described improvements of hepatic microcirculation in patients with nonalcoholic steatohepatitis (NASH) following treatment with LOLA. Mechanisms responsible for the beneficial effects of LOLA in NAFLD/NASH involve, in addition to its established ammonia-lowering effect, metabolic transformations of the LOLA-constituent amino acids L-ornithine and L-aspartate into L-glutamine, L-arginine, and glutathione. These metabolites have well-established actions implicated in the prevention of lipid peroxidation, improvement of hepatic microcirculation in addition to anti-inflammatory, and anti-oxidant properties.Key messages.(1) LOLA is effective for the treatment of key indices in NAFLD/NASH. (2) Mechanisms other than LOLA’s ammonia-lowering action have been postulated. (3) Further assessments in the clinical setting are now required.