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

Crit Care Med. 2002 Sep;30(9):2083-90. doi: 10.1097/00003246-200209000-00022.


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 bacteria suspended in a 30-mL saline solution containing 2-5 x 10(11) 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. 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 Pao similar to severe sepsis in human patients who meet the criteria for acute respiratory distress syndrome (PaO2 /FIO2 <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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Female
  • Hemodynamics
  • Models, Animal
  • Nitric Oxide / blood
  • Nitric Oxide Synthase / metabolism
  • Nitric Oxide Synthase Type II
  • Pseudomonas Infections / etiology*
  • Pseudomonas Infections / metabolism
  • Respiratory Distress Syndrome / complications
  • Respiratory Distress Syndrome / metabolism*
  • Respiratory Distress Syndrome / pathology
  • Sepsis / etiology*
  • Sepsis / metabolism
  • Sheep
  • Smoke Inhalation Injury / complications
  • Smoke Inhalation Injury / metabolism*
  • Smoke Inhalation Injury / pathology


  • Nitric Oxide
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II