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The hydrogen sulfide donor IK‐1001 improves the outcome of acute respiratory distress syndrome in murine and ovine models
Author(s) -
Esechie Aimalohi,
Enkhbaatar Perenlei,
Djukom Clarisse,
Atsumori Hamahata,
Bolanowski David,
Kiss Levente,
Horvath Eszter,
Traber Lilian,
Traber Daniel,
Szabo Csaba
Publication year - 2008
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.22.1_supplement.747.8
Subject(s) - ards , hydrogen sulfide , saline , lung , medicine , smoke inhalation , inhalation , respiratory distress , anesthesia , sulfide , pharmacology , chemistry , sulfur , organic chemistry
The novel biological mediator hydrogen sulfide (H2S) has beneficial effects as a vasodilator, a cytoprotectant and as an anti‐inflammatory agent. Using IK‐1001, an aqueous formulation of H2S, here we tested the effects of hydrogen sulfide in models of acute respiratory distress syndrome (ARDS) in mice and sheep. In the mouse model of 40% third degree burn and smoke inhalation injury, median survival was 22 hours after injury in the vehicle group. At 24h, 33.3% of the control animals were alive. There was a significant increase in median survival in the mice that received hydrogen sulfide treatment after injury (p<0.02; 75 hours). In the same group, 8 out of 12 of the animals were alive during the first 24h. IK‐1001 significantly reduced the level of the pro‐inflammatory cytokine (pg/mg ± SE) in the lung by 50% when compared with the control animals, as measured at 12h in lung homogenates. In the presence of acute lung injury and saline treatment, IL‐10 concentration was unaffected compared with the sham (without burn and smoke) group. However, there was a 2‐fold increase in IL‐10 concentration in the lung after injury and treatment with IK‐1001 (p < 0.05). IK‐1001 was next tested in a clinically relevant LD100 sheep model of ARDS. IK‐1001 significantly prolonged survival and improved PaO2/FiO2. Our results demonstrate the protective effects of hydrogen sulfide in two different experimental models of ARDS.