Novel ovine model of methicillin-resistant Staphylococcus aureus-induced pneumonia and sepsis

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

Research output: Contribution to journalArticle

24 Citations (Scopus)

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°C). Methicillin-resistant S. aureus (AW6) (~2.5 × 10 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 h 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.

Original languageEnglish (US)
Pages (from-to)642-649
Number of pages8
JournalShock
Volume29
Issue number5
DOIs
StatePublished - May 2008

Fingerprint

Staphylococcal Pneumonia
Methicillin-Resistant Staphylococcus aureus
Sheep
Sepsis
Smoke
Inhalation
Lung
Pressure
Gases
Oxygen
Reactive Nitrogen Species
Bronchoscopes
Atrial Pressure
Water-Electrolyte Balance
Multiple Organ Failure
Tracheostomy
Wounds and Injuries
Nitrites
Hematocrit
Artificial Respiration

Keywords

  • Pneumonia
  • Sepsis
  • Smoke

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Physiology

Cite this

Novel ovine model of methicillin-resistant Staphylococcus aureus-induced pneumonia and sepsis. / Enkhbaatar, Perenlei; Joncam, Collette; Traber, Lillian; Nakano, Yoshimitsu; Wang, Jianpu; Lange, Matthias; Connelly, Rhykka; Kulp, Gabriela; Saunders, Fiona; Huda, Ruksana; Cox, Robert; Schmalstieg, Frank; Herndon, David; Traber, Daniel.

In: Shock, Vol. 29, No. 5, 05.2008, p. 642-649.

Research output: Contribution to journalArticle

Enkhbaatar, P, Joncam, C, Traber, L, Nakano, Y, Wang, J, Lange, M, Connelly, R, Kulp, G, Saunders, F, Huda, R, Cox, R, Schmalstieg, F, Herndon, D & Traber, D 2008, 'Novel ovine model of methicillin-resistant Staphylococcus aureus-induced pneumonia and sepsis', Shock, vol. 29, no. 5, pp. 642-649. https://doi.org/10.1097/SHK.0b013e318158125b
Enkhbaatar, Perenlei ; Joncam, Collette ; Traber, Lillian ; Nakano, Yoshimitsu ; Wang, Jianpu ; Lange, Matthias ; Connelly, Rhykka ; Kulp, Gabriela ; Saunders, Fiona ; Huda, Ruksana ; Cox, Robert ; Schmalstieg, Frank ; Herndon, David ; Traber, Daniel. / Novel ovine model of methicillin-resistant Staphylococcus aureus-induced pneumonia and sepsis. In: Shock. 2008 ; Vol. 29, No. 5. pp. 642-649.
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