The inhibition of inducible nitric oxide synthase in ovine sepsis model

Perenlei Enkhbaatar, Kazunori Murakami, Lillian D. Traber, Robert Cox, John F. Parkinson, Martin Westphal, Aimalohi Esechie, Naoki Morita, Marc O. Maybauer, Dirk M. Maybauer, Ann S. Burke, Frank C. Schmalstieg, Hal K. Hawkins, David N. Herndon, Daniel L. Traber

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

Excessive NO has been shown to play a major role in the pathogenesis of multiple organ dysfunctions in septic condition. Burn injury, especially if it is associated with smoke inhalation, is often complicated by subsequent development of pneumonia or sepsis that determine the outcome. In the present study, we developed an ovine sepsis model, created by exposing sheep to smoke inhalation followed by instillation of bacteria into the airway, that closely mimics human sepsis and pneumonia. We hypothesized that the inhibition of iNOS-derived excessive NO might be beneficial in treating the cardiopulmonary derangement in this model. Female sheep (n = 18) were surgically prepared for the study and given a tracheostomy. This was followed by insufflation of 48 breaths of cotton smoke (<40°C) into the airway of each animal and subsequent instillation of live Pseudomonas aeruginosa (5 × 10 11 colony forming units) into each sheep's lung. All sheep were mechanically ventilated using 100% O2. Continuous infusion of BBS-2 (100 μg/kg/h), an iNOS inhibitor, was started 1 h after insult. The administration of BBS-2 improved pulmonary gas exchange (PaO2/ FiO2 and pulmonary shunt fraction) and partially reduced airway obstruction and an increase in ventilatory pressures. The lung water content was not affected by iNOS inhibition. The hypotension seen in nontreated animals was not ameliorated either. The increase in plasma concentration of nitrate and nitrite was inhibited by BBS-2. The results of present study show that iNOS may be partially involved in the pathogenesis of acute lung injury induced by smoke inhalation followed by bacterial instillation in the airway.

Original languageEnglish (US)
Pages (from-to)522-527
Number of pages6
JournalShock
Volume25
Issue number5
DOIs
StatePublished - May 1 2006

Keywords

  • ARDS
  • Pneumonia
  • Smoke inhalation

ASJC Scopus subject areas

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

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  • Cite this

    Enkhbaatar, P., Murakami, K., Traber, L. D., Cox, R., Parkinson, J. F., Westphal, M., Esechie, A., Morita, N., Maybauer, M. O., Maybauer, D. M., Burke, A. S., Schmalstieg, F. C., Hawkins, H. K., Herndon, D. N., & Traber, D. L. (2006). The inhibition of inducible nitric oxide synthase in ovine sepsis model. Shock, 25(5), 522-527. https://doi.org/10.1097/01.shk.0000209525.50990.28