Beneficial effect of a hydrogen sulphide donor (sodium sulphide) in an ovine model of burn‐ and smoke‐induced acute lung injury

Background and purpose:  The present study investigated whether the pathophysiological changes induced by burn and smoke inhalation are modulated by parenteral administration of Na2S, a H2S donor. Experimental approach:  The study used a total of 16 chronically instrumented, adult female sheep. Na2S...

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Published in:British journal of pharmacology 2009-11, Vol.158 (6), p.1442-1453
Main Authors: Esechie, Aimalohi, Enkhbaatar, Perenlei, Traber, Daniel L, Jonkam, Collette, Lange, Matthias, Hamahata, Atsumori, Djukom, Clarisse, Whorton, Elbert B, Hawkins, Hal K, Traber, Lillian D, Szabo, Csaba
Format: Article
Language:English
Subjects:
acute lung injury
Acute Lung Injury - drug therapy
Acute Lung Injury - etiology
Acute Lung Injury - mortality
Animals
Biological and medical sciences
Blotting, Western
Burns
Burns - complications
Cytochromes c - metabolism
Disease Models, Animal
Enzyme-Linked Immunosorbent Assay
Female
Hydrogen Sulfide - metabolism
hydrogen sulphide
Medical sciences
Nitric Oxide Synthase Type II - metabolism
Pharmacology. Drug treatments
protein oxidation
Research Papers
Sheep
smoke inhalation
Smoke Inhalation Injury - drug therapy
Smoke Inhalation Injury - mortality
Smoke Inhalation Injury - physiopathology
Sulfides - pharmacology
Traumas. Diseases due to physical agents
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Summary:Background and purpose:  The present study investigated whether the pathophysiological changes induced by burn and smoke inhalation are modulated by parenteral administration of Na2S, a H2S donor. Experimental approach:  The study used a total of 16 chronically instrumented, adult female sheep. Na2S was administered 1 h post injury, as a bolus injection at a dose of 0.5 mg·kg−1 and subsequently, as a continuous infusion at a rate of 0.2 mg·kg−1·h−1 for 24 h. Cardiopulmonary variables (mean arterial and pulmonary arterial blood pressure, cardiac output, ventricular stroke work index, vascular resistance) and arterial and mixed venous blood gases were measured. Lung wet‐to‐dry ratio and myeloperoxidase content and protein oxidation and nitration were also measured. In addition, lung inducible nitric oxide synthase expression and cytochrome c were measured in lung homogenates via Western blotting and enzyme‐linked immunosorbent assay (elisa) respectively. Key results:  The H2S donor decreased mortality during the 96 h experimental period, improved pulmonary gas exchange and lowered further increase in inspiratory pressure and fluid accumulation associated with burn‐ and smoke‐induced acute lung injury. Further, the H2S donor treatment reduced the presence of protein oxidation and 3‐nitrotyrosine formation following burn and smoke inhalation injury. Conclusions and implications:  Parenteral administration of the H2S donor ameliorated the pulmonary pathophysiological changes associated with burn‐ and smoke‐induced acute lung injury. Based on the effect of H2S observed in this clinically relevant model of disease, we propose that treatment with H2S or its donors may represent a potential therapeutic strategy in managing patients with acute lung injury.
ISSN:0007-1188
1476-5381
DOI:10.1111/j.1476-5381.2009.00411.x