• Aimalohi Esechie, Perenlei Enkhbaatar, Daniel L Traber, Collette Jonkam, Matthias Lange, Atsumori Hamahata, Clarisse Djukom, Elbert B Whorton, Hal K Hawkins, Lillian D Traber, and Csaba Szabo.
• Department of Neuroscience and Cell Biology, The University of Texas Medical Branch, Galveston, 77550, USA.
• Br. J. Pharmacol. 2009 Nov 1;158(6):1442-53.

Background And PurposeThe present study investigated whether the pathophysiological changes induced by burn and smoke inhalation are modulated by parenteral administration of Na(2)S, a H(2)S donor.Experimental ApproachThe study used a total of 16 chronically instrumented, adult female sheep. Na(2)S 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 ResultsThe H(2)S 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 H(2)S donor treatment reduced the presence of protein oxidation and 3-nitrotyrosine formation following burn and smoke inhalation injury.Conclusions And ImplicationsParenteral administration of the H(2)S donor ameliorated the pulmonary pathophysiological changes associated with burn- and smoke-induced acute lung injury. Based on the effect of H(2)S observed in this clinically relevant model of disease, we propose that treatment with H(2)S or its donors may represent a potential therapeutic strategy in managing patients with acute lung injury.

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