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The liver is a critical site for hydrogen sulfide clearance in sepsis
Author(s) -
Norris Eric,
Narasimhan Sriram,
Culberson Cathy,
Clemens Mark G.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1117.8
Subject(s) - sepsis , hydrogen sulfide , perfusion , clearance , chemistry , medicine , endocrinology , urology , sulfur , organic chemistry
Liver dysfunction in sepsis is associated with impaired tissue O 2 availability. Hydrogen sulfide (H 2 S) is a gaseous signaling molecule produced endogenously via Cystathionine γ lyase and its synthesis is upregulated in sepsis. Furthermore, bacteria in the GI tract synthesize H 2 S, exposing the liver to elevated H 2 S. We hypothesized that the liver can metabolize H 2 S and that this capacity is decreased in sepsis. Using an isolated perfused rat liver and heart, we measured H 2 S clearance from the perfusate following perfusion with increasing concentrations of the H 2 S donor Na 2 S (50–500 μM) in the inflow. At Na 2 S concentrations below 150μM, the liver cleared > 90% of the H 2 S; however, at higher Na 2 S levels clearance was progressively inhibited such that absolute clearance was decreased to about 35% of peak rate at Na 2 S above 300 μM. This effect was specific to the liver, as the heart failed to clear Na 2 S at any concentration. H 2 S clearance resulted in an increase in O 2 extraction from the perfusate such that at inflow PO 2 < 300 mmHg, outflow PO 2 was essentially 0. Livers from rats subjected to cecal ligation and puncture showed the same H 2 S clearance capacity indicating that H 2 S oxidation remains a priority in sepsis. Thus, the liver is an important site for H 2 S clearance and elevated H 2 S delivery to the liver in sepsis may be an important determinant of hepatic oxygen availability. Supported by DK38201 and ARRA supplement.