Effects of inhaled nitric oxide in a rat model of Pseudomonas aeruginosa pneumonia

Objective: Antimicrobial effects of nitric oxide (NO) have been demonstrate d in vitro against a Variety of infectious pathogens, yet in vivo evidence of a potential therapeutic role for exogenous NO as an antimicrobial agent is limited. Thus, we assessed the effects of inhaled NO on pulmonary infect ion, leukocyte infiltration, and NO synthase (NOS) activity in a rat model of Pseudomonas aeruginosa pneumonia, Design: Controlled animal study. Setting: Research laboratory of an academic institution. Subjects: Male Sprague-Dawley rats. Interventions: After intratracheal instillation of either P. aeruginosa or saline (sham), rats were randomly exposed to either 40 ppm of inhaled NO or room air (RA) for 24 hrs before they were killed, Measurements and Main Results: Inhaled NO in pneumonia rats markedly reduce d pulmonary bacterial load (0.02 +/- 0.01% vs. 0.99 +/- 0.59% of bacterial input in pneumonia with room air, p < .05) and pulmonary myeloperoxidase ac tivity, a marker of leukocyte infiltration (21.7 +/- 3.8 vs. 55.0 +/- 8.1 u nits in pneumonia with room air, p < .05), but had no effect on systemic he modynamics or gas exchange. Pneumonia was associated with enhanced pulmonar y NOS activity (8.8 +/- 2.4 vs. 0.2 +/- 0.1 pmol citrulline/min/mg protein in sham, p < .01) and increased plasma levels of nitrites/nitrates (NOx-; 4 5 +/- 7 vs. 16 +/- 3 mu mol/L in sham, p < .01). Inhaled NO therapy attenua ted the pneumonia-induced increase in pulmonary calcium-independent NOS act ivity (p < .05) and markedly increased plasma NO; levels. Exposure of P. ae ruginosa in culture to 40 ppm of ambient NO confirmed a delayed antibacteri al effect of NO in vitro. Conclusions: Inhaled NO has an important antibacterial effect both in vitro and in vivo against P. aeruginosa and is associated with reduced pulmonary leukocyte infiltration in vivo. These results in a rat model of P. aerugin osa pneumonia suggest that future studies should address the possible clini cal effects of inhaled NO therapy in pneumonia.