Role of nitric oxide in vascular permeability after combined burns and smoke inhalation injury

Kazutaka Soejima, Lillian D. Traber, Frank C. Schmalstieg, Hal Hawkins, Jeffrey M. Jodoin, Csaba Szabo, Eva Szabo, Lasio Varig, Andrew Salzman, Daniel L. Traber

Research output: Contribution to journalArticle

108 Scopus citations

Abstract

Patients with severe burn and/or smoke inhalation injury suffer both systemic and pulmonary vascular hyperpermeability. We hypothesized that nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) plays a role in the changes in microvascular permeability seen with this injury. To test the hypothesis, we administered mercaptoethylguanidine (MEG), a selective iNOS inhibitor, to conscious sheep subjected to a combined smoke inhalation and third-degree burn injury to 40% of total body surface area. The sheep were surgically prepared for chronic study with lung and prefemoral lymph fistulas in order to estimate microvascular permeability. Both the groups and a control group of animals showed an increase in iNOS protein and message in their lungs. The control animals showed significant increases in either plasma or lymph NO2-/NO3- (NOx) concentration at 24 h after injury, with associated cardiac depression and hemoconcentration. The airway epithelium stained for nitrotyrosine. In the treatment group, NOx did not increase significantly in plasma or lymph throughout the experiment, there was no nitrotyrosine staining, hemodynamic depression was not observed, and the fluid requirement was significantly less than in the control group. Changes in pulmonary microvascular permeability were significantly suppressed by inhibition of iNOS. However, there was no significant difference between the two study groups in the microvascular permeability of burned tissue. These data suggest that NO produced by iNOS plays an important role in the changes in systemic and pulmonary microvascular permeability in combined smoke inhalation/third-degree burn injury, but does not affect the vascular permeability of third-degree-burned tissue in this type of injury.

Original languageEnglish (US)
Pages (from-to)745-752
Number of pages8
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume163
Issue number3 I
DOIs
StatePublished - Jan 1 2001

ASJC Scopus subject areas

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

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    Soejima, K., Traber, L. D., Schmalstieg, F. C., Hawkins, H., Jodoin, J. M., Szabo, C., Szabo, E., Varig, L., Salzman, A., & Traber, D. L. (2001). Role of nitric oxide in vascular permeability after combined burns and smoke inhalation injury. American Journal of Respiratory and Critical Care Medicine, 163(3 I), 745-752. https://doi.org/10.1164/ajrccm.163.3.9912052