TY - JOUR
T1 - A murine model of sepsis following smoke inhalation injury
AU - Lange, Matthias
AU - Hamahata, Atsumori
AU - Traber, Daniel L.
AU - Esechie, Aimalohi
AU - Jonkam, Collette
AU - Bansal, Kamna
AU - Nakano, Yoshimitsu
AU - Traber, Lillian D.
AU - Enkhbaatar, Perenlei
N1 - Funding Information:
This study was supported by Grant 0565028Y from the American Heart Association .
PY - 2010/1/15
Y1 - 2010/1/15
N2 - Acute lung injury (ALI) by smoke inhalation with subsequent pneumonia and sepsis represents a major cause of morbidity and mortality in burn patients. The aim of the present study was to develop a murine model of ALI and sepsis to enhance the knowledge of mechanistic aspects and pathophysiological changes in patients with these injuries. In deeply anesthetized female C57BL/6 mice, injury was induced by four sets of cotton smoke using an inhalation chamber. Afterward, live Pseudomonas aeruginosa (3.2 × 107 colony-forming units) was administered intranasally. The indicated dose of bacteria was determined based on the results of a dose-response study (n = 47). The following study groups were monitored for survival over 96 h: (1) sham injury group, (2) only smoke inhalation group, (3) only bacteria group, and (4) smoke inhalation plus bacteria group. Each group included 10 mice. The survival rates were 100%, 90%, 30%, and 10%, respectively. The double hit injury was associated with excessive releases of pro-inflammatory cytokines in the plasma, and enhanced neutrophil accumulation, increased lipid peroxidation, and excessive formation of reactive nitrogen species in the lung. In mice receiving only smoke inhalation injury, no systemic cytokine release and increased lung tissue lipid peroxidation were observed. However, smoke alone significantly increased neutrophil accumulation and formation of reactive nitrogen species in lung tissue. In conclusion, bacterial pneumonia is predominantly responsible for mortality and morbidity in this novel murine model of smoke inhalation and pulmonary sepsis. Reactive oxygen and nitrogen species mediate the severity of lung injury.
AB - Acute lung injury (ALI) by smoke inhalation with subsequent pneumonia and sepsis represents a major cause of morbidity and mortality in burn patients. The aim of the present study was to develop a murine model of ALI and sepsis to enhance the knowledge of mechanistic aspects and pathophysiological changes in patients with these injuries. In deeply anesthetized female C57BL/6 mice, injury was induced by four sets of cotton smoke using an inhalation chamber. Afterward, live Pseudomonas aeruginosa (3.2 × 107 colony-forming units) was administered intranasally. The indicated dose of bacteria was determined based on the results of a dose-response study (n = 47). The following study groups were monitored for survival over 96 h: (1) sham injury group, (2) only smoke inhalation group, (3) only bacteria group, and (4) smoke inhalation plus bacteria group. Each group included 10 mice. The survival rates were 100%, 90%, 30%, and 10%, respectively. The double hit injury was associated with excessive releases of pro-inflammatory cytokines in the plasma, and enhanced neutrophil accumulation, increased lipid peroxidation, and excessive formation of reactive nitrogen species in the lung. In mice receiving only smoke inhalation injury, no systemic cytokine release and increased lung tissue lipid peroxidation were observed. However, smoke alone significantly increased neutrophil accumulation and formation of reactive nitrogen species in lung tissue. In conclusion, bacterial pneumonia is predominantly responsible for mortality and morbidity in this novel murine model of smoke inhalation and pulmonary sepsis. Reactive oxygen and nitrogen species mediate the severity of lung injury.
KW - Acute lung injury
KW - Mice
KW - Sepsis
KW - Smoke inhalation
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U2 - 10.1016/j.bbrc.2009.12.124
DO - 10.1016/j.bbrc.2009.12.124
M3 - Article
C2 - 20036639
AN - SCOPUS:73949152866
SN - 0006-291X
VL - 391
SP - 1555
EP - 1560
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -