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

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Abstract
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/Fio2 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.