Beneficial effects of nitric oxide inhalation on pulmonary bacterial clearance.
OBJECTIVE
The beneficial effects of nitric oxide inhalation on oxygenation during acute respiratory distress syndrome are well described. In contrast, the effects of nitric oxide on pulmonary inflammatory response are much less known in vivo. The objectives of this study were to evaluate the effects of nitric oxide inhalation on bacterial clearance during bacterial pneumonia and on alveolar neutrophil functions.


METHODS
Controlled animal study.


METHODS
Research laboratory of an academic institution.


METHODS
Male Sprague-Dawley rats.


METHODS
Severe pneumonia was induced by alveolar instillation of live Pseudomonas aeruginosa (1.5 x 10(8) colony-forming units/kg) in rats. After instillation, rats were exposed to oxygen alone (FIO(2) 100%) or to oxygen (FIO(2) approximately 100%) plus nitric oxide (10 ppm) during 24 hrs.


RESULTS
Oxygen plus nitric oxide inhalation compared with oxygen alone increased recruitment of alveolar neutrophils (32.5 +/- 4.6 x 10(6) cells/mL vs. 23.4 +/- 1.9 x 10(6) cells/mL, p <.05) and improved bacterial clearance in the bronchoalveolar lavage fluid (8.1 +/- 4.2 x 10(2) vs. 1.6 +/- 1.0 x 10(5) colony-forming units/mL, p <.05) and in the pulmonary parenchyma (1.7 +/- 1.14 x 10(7) vs. 3.4 +/- 1.5 x 10(8) colony-forming units/mL, p <.05). However, neither protein concentration in the bronchoalveolar lavage fluid nor mortality rates were modified by nitric oxide inhalation. The ex vivo alveolar neutrophil functions were similar regardless of whether rats previously inhaled nitric oxide. In vitro experiments demonstrated that nitric oxide donor had a direct bactericidal effect against P. aeruginosa and did not modify alveolar neutrophil functions.


CONCLUSIONS
These results suggest a beneficial effect of nitric oxide inhalation on bacterial clearance of P. aeruginosa attributable to both a direct bactericidal effect and an influx of alveolar neutrophils with preserved functions.
Jean
Daniel
D
Institut National de la Santé et de la Recherche Médicale, Hôpital Henri Mondor-Assistance Publique des Hôpitaux de Paris, Créteil, France.
Maître
Bernard
B
Tankovic
Jacques
J
Meignan
Michel
M
Adnot
Serge
S
Brun-Buisson
Christian
C
Harf
Alain
A
Delclaux
Christophe
C
D000280:Administration, Inhalation; D000818:Animals; D001770:Blood Bactericidal Activity / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D015169:Colony Count, Microbial; D066298:In Vitro Techniques; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D020556:Neutrophil Infiltration / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000494:pharmacology / Q000627:therapeutic use*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D016877:Oxidants / Q000378:metabolism; D010196:Pancreatic Elastase / Q000378:metabolism; D018410:Pneumonia, Bacterial / Q000150:complications / Q000188:drug therapy*; D011650:Pulmonary Alveoli / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000188:drug therapy* / Q000382:microbiology
D020030:Nitric Oxide Donors; D016877:Oxidants; D009569:Nitric Oxide; C002385:linsidomine; D008981:Molsidomine; D010196:Pancreatic Elastase