The inducible nitric oxide synthase inhibitor BBS-2 prevents acute lung injury in sheep after burn and smoke inhalation injury

Perenlei Enkhbaatar, Kazunori Murakami, Katsumi Shimoda, Akio Mizutani, Lillian Traber, Gary B. Phillips, John F. Parkinson, Robert Cox, Hal Hawkins, David Herndon, Daniel Traber

Research output: Contribution to journalArticle

108 Scopus citations

Abstract

In this study we examined the role of inducible nitric oxide synthase (iNOS) in acute respiratory distress syndrome (ARDS) in sheep with severe combined burn and smoke inhalation injury. BBS-2, a potent and highly selective iNOS dimerization inhibitor, was used to exclude effects on the endothelial and neuronal NOS isoforms. Seven days after surgical recovery, sheep were given a burn (40% of total body surface, 3rd degree) and insufflated with cotton smoke (48 breaths, < 40°C) under anesthesia. BBS-2 was provided by constant infusion at 100 μg/kg/hour, beginning 1 hour after injury. During 48 hours, control sheep developed multiple signs of ARDS. These included decreased pulmonary gas exchange, increased pulmonary edema, abnormal lung compliance, and extensive airway obstruction. These pathologies were associated with a large increase in tracheal blood flow and elevated plasma NO2- /NO3- (NOx) levels. These variables were all stable in sham animals. Treatment of injured sheep with BBS-2 attenuated the increases in tracheal blood flow and plasma NOx levels, and significantly attenuated all the pulmonary pathologies that were noted. The results provide definitive evidence that iNOS is a key mediator of pulmonary pathology in sheep with ARDS resulting from combined burn and smoke inhalation injury.

Original languageEnglish (US)
Pages (from-to)1021-1026
Number of pages6
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume167
Issue number7
DOIs
StatePublished - Apr 1 2003

Keywords

  • Acute respiratory distress syndrome
  • Nitric oxide
  • Thermal injury

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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