Assessment of Lung Inflammation in a Mouse Model of Smoke Inhalation and Burn Injury: Strain-Specific Differences

ABSTRACT

To test concepts developed in our ovine model of acute respiratory distress syndrome, specifically the roles of neuropeptides and other peptide mediators, a recently developed murine model of combined smoke inhalation and burn (SB) injury was extended by applying methods for quantitative assessment of acute inflammation in the lung. Mice received SB injury per protocol, n = 5 to 7 per group. Mice were anesthetized with i.p. ketamine/xylazine, endotracheally intubated, and exposed to cooled cotton smoke (4 × 30 sec for Balb/C, 2 × 30 sec for C57BL/6). After s.c. injection of 1 mL 0.9% saline, each received a 40% total body surface area (TBSA) flame burn. Buprenorphine (0.1 mg/kg) was given i.p. for postoperative analgesia; 0.9% saline was given i.p. at 4 mL/kg per %TBSA burn. Evans Blue dye (EB) was injected i.v. 15 min before sacrifice. Lung wet/dry weight ratio was measured. In other animals, after vascular perfusion with buffered saline, lungs were sampled and analyzed for myeloperoxidase (MPO), using an EIA kit, and for their content of EB dye.

There was a significant (p < 0.05) increase in EB dye content, wet/dry weight ratio, and MPO 24 h after injury in Balb/C mice. Similar increases were seen in C57BL/6 mice 48 h after SB injury, but not at 24 h. C57 mice tolerated less smoke inhalation than Balb/C mice, due to postexposure apnea, and required 48 h to show significant increases in these variables. Direct comparison between animals injured by 40% TBSA burn and 2 × 30 sec smoke exposure and sacrificed after 48 h showed significantly greater abnormality in the C57BL/6 mice. The mouse model can be used effectively to assess acute inflammation in the lung.

This work was supported by a program project grant from NIH, #NIGMS PO1-GM66312, in laboratory facilities provided by the Shriners of North America.