Document Detail

Novel ovine model of methicillin-resistant Staphylococcus aureus-induced pneumonia and sepsis.
MedLine Citation:
PMID:  17885644     Owner:  NLM     Status:  MEDLINE    
Methicillin-resistant Staphylococcus aureus (MRSA)-related pneumonia and/or sepsis are a frequent serious menace. The aim of the study was to establish a standardized and reproducible model of MRSA-induced septic pneumonia to evaluate new therapies. Sheep were operatively prepared for chronic study. After 5 days' recovery, tracheostomy was performed under anesthesia, and smoke injury was induced by inhalation of cotton smoke (48 breaths, <40 degrees C). Methicillin-resistant S. aureus (AW6) (approximately 2.5x10(11) colony-forming units) was instilled into the airway by a bronchoscope. After the injury, animals were awakened and maintained on mechanical ventilation by 100% oxygen for first 3 h, and thereafter, oxygen concentration was adjusted according to blood gases. The sheep were resuscitated by lactated Ringer solution with an initial rate of 2 mL kg(-1) h(-1) that was further adjusted according to hematocrit. Study groups include (1) sham (noninjured, nontreated; n=6), (2) S+MRSA (exposed to smoke inhalation and MRSA, nontreated; n=6), and (3) smoke (exposed to smoke inhalation alone; n=6). Injured (S+MRSA) animals showed the signs of severe sepsis-related multiple organ failure 3 h after insult. Cardiovascular morbidity was evidenced by severe hypotension, with increased heart rate, cardiac output, left atrial pressure and severely decreased systemic vascular resistance index, and left ventricle stroke work index. Pulmonary dysfunction was characterized by deteriorated gas exchange (PaO2/FIO2 and pulmonary shunt) and increased ventilatory pressures. The S+MRSA group showed significantly greater lung tissue water content, myeloperoxidase activity, and cytokine production compared with uninjured sham animals. Microvascular hyperpermeability was evidenced by marked fluid retention (fluid net balance), decreased plasma protein with decreased plasma oncotic pressure, and increased pulmonary microvascular pressure. All these changes were accompanied by 6- to 7-fold increase in plasma nitrite/nitrate and increased production of reactive nitrogen species in lung. The smoke inhalation alone had a little or no effect on these variables. This model closely mimics hyperdynamic human sepsis. The excessive production of NO may be extensively involved in the pathogenic process.
Perenlei Enkhbaatar; Collette Joncam; Lillian Traber; Yoshimitsu Nakano; Jianpu Wang; Matthias Lange; Rhykka Connelly; Gabriela Kulp; Fiona Saunders; Ruksana Huda; Robert Cox; Frank Schmalstieg; David Herndon; Daniel Traber
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Shock (Augusta, Ga.)     Volume:  29     ISSN:  1073-2322     ISO Abbreviation:  Shock     Publication Date:  2008 May 
Date Detail:
Created Date:  2008-05-07     Completed Date:  2008-06-09     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9421564     Medline TA:  Shock     Country:  United States    
Other Details:
Languages:  eng     Pagination:  642-9     Citation Subset:  IM    
Department of Anesthesiology, University of Texas Medical Branch, and Shriners Hospital for Children, Galveston, TX 77551, USA.
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MeSH Terms
Disease Models, Animal
Lung / pathology
Methicillin / pharmacology*
Methicillin Resistance*
Pneumonia / microbiology*
Sepsis / microbiology*
Smoke Inhalation Injury
Staphylococcus aureus / metabolism*
Time Factors
Tyrosine / analogs & derivatives,  metabolism
Reg. No./Substance:
3604-79-3/3-nitrotyrosine; 55520-40-6/Tyrosine; 61-32-5/Methicillin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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