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

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.