The inducible nitric oxide synthase inhibitor BBS-2 prevents acute lung injury in sheep after burn and smoke inhalation injury. American journal of respiratory and critical care medicine. [Am J Respir Crit Care Med] Journal article | | Title | The inducible nitric oxide synthase inhibitor BBS-2 prevents acute lung injury in sheep after burn and smoke inhalation injury. | | Author(s) | Enkhbaatar P, Murakami K, Shimoda K, Mizutani A, Traber L, Phillips GB, Parkinson JF, Cox R, Hawkins H, Herndon D, Traber D | | Institution | Department of Anesthesiology, University of Texas Medical Branch, 610 Texas Ave, Galveston, TX 77555, USA. | | Source | Am J Respir Crit Care Med 2003 Apr 1; 167(7):1021-6. | | MeSH | Animals
Blood Pressure
Body Surface Area
Burns
Comparative Study
Disease Models, Animal
Enzyme Inhibitors
Extravascular Lung Water
Female
Heart Rate
Lymph Nodes
Models, Cardiovascular
Nitrates
Nitric Oxide Synthase
Nitric Oxide Synthase Type II
Nitrites
Proteins
Pulmonary Circulation
Pulmonary Gas Exchange
Respiratory Distress Syndrome, Adult
Severity of Illness Index
Sheep
Smoke Inhalation Injury
Time Factors
Treatment Outcome
| | 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 degrees C) under anesthesia. BBS-2 was provided by constant infusion at 100 microg/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. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 12663341 |
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