The effect of inducible nitric oxide synthase (iNOS) inhibition on smoke inhalation injury in sheep

Kazutaka Soejima, Roy McGuire, Ned Snyder IV, Tatsuo Uchida, Csaba Szabó, Andrew Salzman, Lillian D. Traber, Daniel L. Traber

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    42 Scopus citations

    Abstract

    Recent studies on smoke inhalation injury have been focused on nitric oxide (NO) as an essential factor of progressive lung injury. We studied the effects of inducible nitric oxide synthase (iNOS) inhibition on inhalation injury in sheep. Sheep (n = 14) were prepared surgically for chronic study. After recovery period, the sheep received 48 breaths of cotton smoke. The animals were then randomised into two groups: MEG group [30 mg/kg mercaptoethylguanidine (MEG), selective inhibitor of iNOS and peroxynitrite scavenger, was given 1 h after injury and then 8 h for 41 h, n = 7] and control group (0.9% NaCl, n = 7). All animals were ventilated mechanically, and airway blood flow was measured using colored microspheres. In the control group, following significant increase in airway blood flow, deterioration in the PaO2/FiO2 ratio was observed. Whereas in the MEG group, it was not observed. In addition, the MEG group did not show significant increase in pulmonary vascular resistance and intrapulmonary shunt fraction. Lung wet/dry ratios, a marker of pulmonary edema, were significantly lower in the MEG group. At 48 h after injury, lung tissue-conjugated dienes, an index of lung oxidative tissue injury, were significantly lower in the MEG group than in the control group. Our data suggest that 1) iNOS-NO produced in the airway circulation plays a major role on the significant increase in airway blood flow, which may contribute to the spread of injury from injured airway to the lung parenchyma; 2) iNOS-NO induced in the pulmonary circulation contributes to the loss of hypoxic pulmonary vasoconstriction; and 3) iNOS-NO plays an important role on the lung oxidative tissue injury.

    Original languageEnglish (US)
    Pages (from-to)261-266
    Number of pages6
    JournalShock
    Volume13
    Issue number4
    DOIs
    StatePublished - Apr 2000

    Keywords

    • Airway blood flow
    • Hypoxic pulmonary vasoconstriction
    • Oxidative lung tissue injury
    • Oxygen free radical
    • Peroxynitrite

    ASJC Scopus subject areas

    • Emergency Medicine
    • Critical Care and Intensive Care Medicine

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  • Cite this

    Soejima, K., McGuire, R., Snyder IV, N., Uchida, T., Szabó, C., Salzman, A., Traber, L. D., & Traber, D. L. (2000). The effect of inducible nitric oxide synthase (iNOS) inhibition on smoke inhalation injury in sheep. Shock, 13(4), 261-266. https://doi.org/10.1097/00024382-200004000-00002