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

Area of Science:

• Immunology
• Gastroenterology
• Physiology

Background:

• Sepsis-induced microcirculatory and mitochondrial dysfunction in the gastrointestinal system significantly contribute to mortality.
• Hydrogen sulfide (H2S) plays a crucial role in optimizing gastrointestinal oxygen supply and mitochondrial respiration, primarily through K(ATP)-channels.

Purpose of the Study:

• To investigate the hypothesis that sodium thiosulfate (STS), an inducer of endogenous H2S, can improve intestinal and hepatic microcirculation and mitochondrial function in a sepsis model.
• To determine the role of K(ATP)-channels in mediating the potential beneficial effects of STS.

Main Methods:

• Sepsis was induced in Wistar rats using colon ascendens stent peritonitis (CASP) surgery.
• Animals were randomized into groups receiving STS, glibenclamide (GL, a K(ATP)-channel blocker), STS + GL, or vehicle.
• Microcirculatory oxygenation and flow in the colon and liver were continuously monitored using tissue reflectance spectrophotometry.
• Mitochondrial oxygen consumption was assessed via respirometry.

Main Results:

• STS administration significantly increased microcirculatory oxygenation (µHbO2) and blood flow (µflow) in both the colon and liver compared to baseline and vehicle.
• The combination of STS and GL enhanced colonic µHbO2 and µflow, but hepatic microcirculation did not show significant changes.
• Glibenclamide alone did not affect microcirculatory parameters, and mitochondrial oxygen consumption remained unaltered across groups.

Conclusions:

• STS demonstrates a beneficial effect on intestinal and hepatic microcirculatory oxygenation in sepsis, primarily through enhanced perfusion rather than mitochondrial or macrohemodynamic changes.
• The protective effect of STS on hepatic microcirculation appears to be K(ATP)-channel dependent, while its effect on intestinal microcirculation may not be.