HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

The inhibition of inducible nitric oxide synthase in ovine sepsis model.

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 degrees C) into the airway of each animal and subsequent instillation of live Pseudomonas aeruginosa (5 x 10(11) colony forming units) into each sheep's lung. All sheep were mechanically ventilated using 100% O2. Continuous infusion of BBS-2 (100 microg/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.
AuthorsPerenlei 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
JournalShock (Augusta, Ga.) (Shock) Vol. 25 Issue 5 Pg. 522-7 (May 2006) ISSN: 1073-2322 [Print] United States
PMID16680018 (Publication Type: Journal Article)
Chemical References
  • Enzyme Inhibitors
  • Protein Isoforms
  • Nitric Oxide Synthase Type II
Topics
  • Animals
  • Disease Models, Animal
  • Enzyme Inhibitors (pharmacology)
  • Female
  • Lung (microbiology, pathology)
  • Lung Injury
  • Nitric Oxide Synthase Type II (antagonists & inhibitors)
  • Pneumonia (pathology)
  • Protein Isoforms
  • Pseudomonas aeruginosa (metabolism)
  • Sepsis (drug therapy, enzymology, pathology)
  • Sheep
  • Smoke Inhalation Injury (therapy)
  • Time Factors
  • Tracheostomy

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: