AUTHOR=Schulz Jan , Kramer Sandra , Kanatli Yasin , Kuebart Anne , Bauer Inge , Picker Olaf , Vollmer Christian , Truse Richard , Herminghaus Anna 

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

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.671935

DOI=10.3389/fimmu.2021.671935

ISSN=1664-3224

ABSTRACT=<sec><title>Introduction</title><p>In the immunology of sepsis microcirculatory and mitochondrial dysfunction in the gastrointestinal system are important contributors to mortality. Hydrogen sulfide (H<sub>2</sub>S) optimizes gastrointestinal oxygen supply and mitochondrial respiration predominantly <italic>via</italic> K(ATP)-channels. Therefore, we tested the hypothesis that sodium thiosulfate (STS), an inducer of endogenous H<sub>2</sub>S, improves intestinal and hepatic microcirculation and mitochondrial function <italic>via</italic> K(ATP)-channels in sepsis.</p></sec><sec><title>Methods</title><p>In 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<sup>-1</sup> i.p., 2: glibenclamide (GL) 5 mg • kg<sup>-1</sup> i.p., 3: STS + GL, 4: vehicle (VE) i.p.). Treatment was given directly after CASP-surgery and 24 hours later. Microcirculatory oxygenation (µHBO<sub>2</sub>) 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.</p></sec><sec><title>Results</title><p>STS increased µHbO<sub>2</sub> (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, µHbO<sub>2</sub> and µflow were significantly higher after STS compared to VE. The combination of STS and GL increased colonic µHbO<sub>2</sub> and µflow (µHbO<sub>2</sub> 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 µHbO<sub>2</sub> and µflow did not change after STS and GL. GL alone did not change colonic or hepatic µHbO<sub>2</sub> or µflow. Mitochondrial oxygen consumption and macrohemodynamic remained unaltered.</p></sec><sec><title>Conclusion</title><p>The 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.</p></sec>