The anti-inflammatory effect of inhaled nitric oxide on pulmonary inflammation in a swine model.
Cardiopulmonary bypass (CPB) is associated with an inflammatory process that leads to lung injury. In this study, we hypothesized that inhaled nitric oxide (INO) possesses the ability to modulate CPB-induced inflammation. Fifteen male pigs were randomly divided into 3 groups: Sham, CPB+LPS (CPB and lipopolysaccharide), and CPB+LPS+INO. INO (20 parts per million) was administered for 24 h after anesthesia. CPB was performed for 90 min, and LPS was infused (1 microg/kg) after CPB. Bronchoalveolar lavage (BAL) fluid and blood were collected at T0 (before CPB), at 4 h, and at 24 h. At 24 h, BAL interleukin-8 (IL-8) levels were not increased as expected in the CPB+LPS group compared with the Sham group, but they were reduced significantly in the CPB+LPS+INO group. Cell hypo reactivity observed in the groups receiving LPS also seemed to downregulate endothelial nitric oxide synthase NOS protein expression relative to the Sham group. Nitrite and nitrate (NOx) concentrations were decreased significantly in the groups without INO. Moreover, animals treated with INO showed higher rates of pulmonary apoptosis compared with their respective controls. These results demonstrate that NOx production is reduced after CPB and that INO acts on the inflammatory process by diminishing neutrophils and their major chemoattractant, IL-8. INO also increases cell apoptosis in the lungs under inflammatory conditions, which may explain, in part, how it resolves pulmonary inflammation.
El Kebir
D
D
Laboratory of Anesthesia, Department of Anesthesia, Centre hospitalier de l'Université de Montréal-Hôpital Notre-Dame, QC, Canada.
Taha
R
R
Hubert
B
B
Gauvin
D
D
Gangal
M
M
Blaise
G
G
D000280:Administration, Inhalation; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002315:Cardiopulmonary Bypass; D004195:Disease Models, Animal; D016209:Interleukin-8 / Q000276:immunology; D008070:Lipopolysaccharides; D008168:Lung / Q000187:drug effects* / Q000276:immunology; D008297:Male; D009504:Neutrophils / Q000276:immunology; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000008:administration & dosage / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D009573:Nitrites / Q000097:blood; D011014:Pneumonia / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D013552:Swine
D000893:Anti-Inflammatory Agents; D016209:Interleukin-8; D008070:Lipopolysaccharides; D009566:Nitrates; D009573:Nitrites; C440499:lipopolysaccharide, Escherichia coli O111 B4; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III