Beneficial effects of nitric oxide inhalation on pulmonary bacterial clearance

Abstract

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. DESIGN: Controlled animal study. SETTING: Research laboratory of an academic institution. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: 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. MEASUREMENTS AND MAIN 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.