title: Novel ovine model of methicillin-resistant Staphylococcus aureus-induced pneumonia and sepsis.
abstract: 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.
authors: Department of Anesthesiology, University of Texas Medical Branch, and Shriners Hospital for Children, Galveston, TX 77551, USA. peenkhba@utmb.edu
authors: Perenlei
authors: P
authors: Enkhbaatar
authors: Collette
authors: C
authors: Joncam
authors: Lillian
authors: L
authors: Traber
authors: Yoshimitsu
authors: Y
authors: Nakano
authors: Jianpu
authors: J
authors: Wang
authors: Matthias
authors: M
authors: Lange
authors: Rhykka
authors: R
authors: Connelly
authors: Gabriela
authors: G
authors: Kulp
authors: Fiona
authors: F
authors: Saunders
authors: Ruksana
authors: R
authors: Huda
authors: Robert
authors: R
authors: Cox
authors: Frank
authors: F
authors: Schmalstieg
authors: David
authors: D
authors: Herndon
authors: Daniel
authors: D
authors: Traber
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006400:Hematocrit; D006439:Hemodynamics; D008168:Lung / Q000473:pathology; D008712:Methicillin / Q000494:pharmacology*; D016106:Methicillin Resistance; D011014:Pneumonia / Q000382:microbiology*; D018805:Sepsis / Q000382:microbiology*; D012756:Sheep; D015208:Smoke Inhalation Injury; D013211:Staphylococcus aureus / Q000378:metabolism*; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: C002744:3-nitrotyrosine; D014443:Tyrosine; D008712:Methicillin