A novel animal model of sepsis after acute lung injury in sheep

Kazunori Murakami, Lars J. Bjertnaes, Frank C. Schmalstieg, Roy McGuire, Robert A. Cox, Hal K. Hawkins, David N. Herndon, Lillian D. Traber, Daniel L. Traber

Research output: Contribution to journalArticlepeer-review

74 Scopus citations


Objective: Patients with acute lung injury after smoke inhalation often develop pneumonia subsequently complicated by sepsis. This often is a fatal complication. The aim of this study was to develop a standardized and reproducible model of hyperdynamic sepsis after smoke inhalation in sheep. Design: Prospective, experimental study in sheep. Settings: Experimental laboratory in a university hospital. Subjects: Twenty-one female Merino ewes. Intervention: Animals were anesthetized and surgically prepared for this chronic study. After a week of recovery, baseline data were collected. After tracheostomy was performed, sheep were connected to a volume-controlled ventilator. Acute lung injury was produced by insufflating the lungs with 48 breaths of cotton smoke. During halothane anesthesia, live Pseudomonas aeruginosa bacteria suspended in a 30-mL saline solution containing 2-5 × 1011 colony-forming units were instilled through a bronchoscope into the right lower and middle lung lobes (10 mL each) and left lower lung lobe (10 mL; n = 10). Eleven sheep were given smoke but not bacteria. After injury and the bacterial challenge, the animals were ventilated mechanically with 100% oxygen. The animals were monitored for 48 hrs. P. aeruginosa was detected in blood cultures after 14-48 hrs. Measurements and Main Results: The sheep developed a hyperkinetic cardiovascular response concomitant with a decrease in Pao2 similar to severe sepsis in human patients who meet the criteria for acute respiratory distress syndrome (Pao2/Flo2 <200). These changes were more severe than in animals exposed to smoke inhalation alone. Mean arterial pressures at 48 hrs in the smoke-alone and the smoke + sepsis group were 85.5 ± 5.2 and 68.1 ± 7.6 mm Hg, respectively (mean ± SE, p < .05). Conclusion: This animal model closely resembles hyperdynamic sepsis in humans and may be of great value for studies of sepsis with smoke inhalation.

Original languageEnglish (US)
Pages (from-to)2083-2090
Number of pages8
JournalCritical care medicine
Issue number9
StatePublished - Sep 1 2002
Externally publishedYes


  • Acute lung injury
  • Acute respiratory distress syndrome
  • Airway cast
  • Histology
  • Hyperdynamic
  • Nitric oxide
  • Pneumonia
  • Pseudomonas aeruginosa
  • Sheep
  • Shock
  • Smoke inhalation

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine


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