Document Detail

Role of neuronal nitric oxide synthase in ovine sepsis model.
MedLine Citation:
PMID:  19008779     Owner:  NLM     Status:  MEDLINE    
Smoke inhalation injury is often complicated with pneumonia, which frequently leads to subsequent development of sepsis. Excessive NO has been shown to mediate many sepsis-related pathological responses. In the present study, we used our well-established ovine smoke inhalation and pneumonia/sepsis model to examine the hypothesis that neuronal NO synthase (NOS) may be primarily responsible for these pathological alterations. We report the beneficial effects of the specific neuronal NOS (nNOS) inhibitor ZK234238. Adult female sheep were surgically prepared for the study. After 5 to 7 days' recovery, sheep were anesthetized and given double injury: 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 via tracheostomy tube. All sheep were mechanically ventilated and fluid resuscitated by lactated Ringer's solution. Sheep were randomly allocated into groups: control (injured not treated, n = 6) and treated (injured, but treated with ZK234238, n = 4). Continuous infusion of ZK234238 (100 microg x kg(-1) x h(-1)) was started 1 h after insult. ZK234238 attenuated the hypotension (at 18 and 24 h) and fall in systemic vascular resistance (at 24 h) seen in control animals. ZK234238 significantly inhibited increased fluid accumulation as well as increased plasma nitrate/nitrite 24 h after injury. Neuronal NOS inhibition significantly reduced lung water content and attenuated inflammatory indices such as lung tissue myeloperoxidase activity, IL-6 mRNA, and reactive nitrogen species. The above results suggest that the nNOS-derived NO may be involved in the pathophysiology of sepsis-related multiorgan dysfunction.
Perenlei Enkhbaatar; Matthias Lange; Yoshimitsu Nakano; Atsumori Hamahata; Collette Jonkam; Jianpu Wang; Stefan Jaroch; Lillian Traber; David Herndon; Daniel Traber
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Shock (Augusta, Ga.)     Volume:  32     ISSN:  1540-0514     ISO Abbreviation:  Shock     Publication Date:  2009 Sep 
Date Detail:
Created Date:  2009-08-20     Completed Date:  2009-12-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9421564     Medline TA:  Shock     Country:  United States    
Other Details:
Languages:  eng     Pagination:  253-7     Citation Subset:  IM    
Department of Anesthesiology, University of Texas Medical Branch, Galveston, Texas 77555, USA.
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MeSH Terms
Disease Models, Animal
Interleukin-6 / genetics
Lung / drug effects,  metabolism,  pathology
Lung Injury / drug therapy,  metabolism,  microbiology,  pathology
Nitrates / blood
Nitric Oxide Synthase Type I / antagonists & inhibitors,  metabolism*
Nitrites / blood
Oxazines / pharmacology,  therapeutic use
Peroxidase / metabolism
Pseudomonas aeruginosa / pathogenicity
Random Allocation
Reactive Nitrogen Species / metabolism
Sepsis / drug therapy,  enzymology*,  metabolism,  pathology
Smoke Inhalation Injury / drug therapy,  metabolism,  pathology
Reg. No./Substance:
0/Interleukin-6; 0/Nitrates; 0/Nitrites; 0/Oxazines; 0/Reactive Nitrogen Species; 0/ZK 234238; EC; EC Oxide Synthase Type I

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