Nitric oxide releasing nanoparticles reduce inflammation in a small animal model of ARDS

Abstract

Acute respiratory distress syndrome (ARDS) is a condition hallmarked by high permeability pulmonary edema and hypoxemic respiratory failure and is associated with high mortality. Current treatment protocols rely on improving O₂ delivery, decreasing O₂ consumption, and treating the underlying cause of the initial insult. In this study, we used a small rodent model of ARDS, where we induced lung injury with inhalation of lipopolysaccharide (LPS). We investigated three different treatments, namely inhaled NO at 70 ppm, inhaled NO at 140 ppm, and NO-np (10 mg/mL), compared with untreated rodents 72 h after initial insult. Concurrent with treatment, the fraction of inspired O₂ was increased after 30 min from 21% to 40% and finally to 60%. At an FiO₂ of 60% and 72 h post induction of ARDS, NO-np treated mice had an arterial PO₂ (PaO₂) of 142 ± 9 mmHg, higher than mice treated with inhaled NO at 70 ppm (87 ± 5 mmHg, p = 8.4 × 10^-8) and inhaled NO at 140 ppm (107 ± 6 mmHg, p = 6.1 × 10^-6). Neutrophils in both the periphery (1.6 × 10⁵ ± 0.4 × 10⁵ cells) and bronchoalveolar lavage fluid (BALF; 2.7 × 10⁵ ± 0.8 × 10⁵ cells) were reduced in NO-np treated mice compared to mice treated with inhaled NO at 70 ppm (p = 0.0097, 2.4 × 10⁵ ± 0.5 × 10⁵ cells for periphery, p = 0.0075, 3.8 × 10⁵ ± 0.8 × 10⁵ cells for BALF). In summary, we found that treatment with NO-np improved arterial PO₂ at a high FiO₂ compared to inhaled NO alone and NO-np reduced both circulating and pulmonary interstitial neutrophil count, while inhaled NO did not. Future studies should aim to elucidate the precise mechanisms behind how NO-np mediate neutrophilic inflammation in ARDS.

Keywords: Acute respiratory distress syndrome; Lipopolysaccharide; NO nanoparticles; Nitric oxide.