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

Vinay P. Jani, Joel M. Friedman, Pedro Cabrales

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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.

Original languageEnglish (US)
Article number112705
JournalBiomedicine and Pharmacotherapy
Volume148
DOIs
StatePublished - Apr 2022

Keywords

  • Acute respiratory distress syndrome
  • Lipopolysaccharide
  • NO nanoparticles
  • Nitric oxide

ASJC Scopus subject areas

  • Pharmacology

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