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Sodium hydrosulfide alleviates cecal ligation and puncture (CLP) ‐ induced sepsis and elevates the regional blood flow in septic shock
Author(s) -
Ahmad Akbar,
Szabo Csaba
Publication year - 2016
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.30.1_supplement.1271.7
Subject(s) - sodium hydrosulfide , sepsis , blood flow , septic shock , medicine , blood urea nitrogen , ligation , renal blood flow , shock (circulatory) , hemodynamics , saline , anesthesia , renal function , chemistry , hydrogen sulfide , sulfur , organic chemistry
Cecal ligation and puncture (CLP) induced sepsis is a serious medical condition, caused by a severe systemic infection resulting in a systemic inflammatory response. The aim of the present study was to assess the effect of hydrogen sulfide in sepsis, with special reference to its effect on the modulation of regional blood flow. To this purpose, we infused sodium hydrosulfide (NaHS) (1 mg/kg/h, 3 mg/kg/h or 10 mg/kg/h through the carotid artery) in control rats or rats 24 hours after CLP measured blood flow using fluorescent microspheres. We have also evaluated the effect of hydrogen sulfide on survival and organ function by injecting NaSH (3 mg/kg) intraperitoneally (i.p) after 24 hrs of CLP. We found that in normal control animals, NaHS induced a characteristic redistribution of blood flow, and reduced cardiac, hepatic and renal blood flow in a dose‐dependent fashion. In contrast, we found that, in rats suffering from CLP‐induced septic shock, the regional blood flow was significantly reduced, and infusion of NaSH (1 mg/kg/h and 3 mg/kg/h) significantly increased the blood flow. In other words, the effect of H 2 S on regional blood flow was dependent on the status of the animals (i.e. a decrease in blood flow in normal controls, but an increase in blood flow in septic animals). After 24 h of CLP, the glomerular function was significantly impaired, as evidenced by markedly increased (over 4‐fold over sham control baseline) blood urea nitrogen and creatinine levels; this increase was also significantly reduced by treatment with NaSH (3 mg/kg i.p). Treatment of the animals with NaSH reduced myeloperoxidase levels (an index of neutrophil infiltration) in heart as well as in lung and malondialdehyde levels (an index of oxidative stress) in heart as well as in liver. Plasma levels of TNF‐alpha and IL‐1beta were increased in septic shock animals, which were attenuated by NaSH. Treatment of NaSH (3 mg/kg i.p) every 6 h after 12 h of CLP improved the survival rate in CLP animals. In summary, delayed treatment with H 2 S (treatment starting after the CLP‐induced organ injury, inflammation and blood flow redistribution has already ensued) dose‐dependently maintains regional blood flow and exerts protective effects in rat model of CLP induced sepsis. Support or Funding Information This work was supported by the National Institutes of Health (R01GM107846) to C.S.