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.


METHODS
Prospective, experimental study in sheep.


METHODS
Experimental laboratory in a university hospital.


METHODS
Twenty-one female Merino ewes.


METHODS
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.


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).


CONCLUSIONS
This animal model closely resembles hyperdynamic sepsis in humans and may be of great value for studies of sepsis with smoke inhalation.
D000818:Animals; D005260:Female; D006439:Hemodynamics; D023421:Models, Animal; D009569:Nitric Oxide / Q000097:blood; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D011552:Pseudomonas Infections / Q000209:etiology* / Q000378:metabolism; D012128:Respiratory Distress Syndrome / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D018805:Sepsis / Q000209:etiology* / Q000378:metabolism; D012756:Sheep; D015208:Smoke Inhalation Injury / Q000150:complications / Q000378:metabolism* / Q000473:pathology
D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II