TY - JOUR
T1 - Nitric oxide releasing nanoparticles reduce inflammation in a small animal model of ARDS
AU - Jani, Vinay P.
AU - Friedman, Joel M.
AU - Cabrales, Pedro
N1 - Funding Information:
The authors would also like to thank Cynthia Walser for animal preparation. This work was supposed by the NIH Heart Lung and Blood Institute under Grants R01-HL126945 and R01-HL138116 .
Publisher Copyright:
© 2022 The Authors
PY - 2022/4
Y1 - 2022/4
N2 - 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.
AB - 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.
KW - Acute respiratory distress syndrome
KW - Lipopolysaccharide
KW - NO nanoparticles
KW - Nitric oxide
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U2 - 10.1016/j.biopha.2022.112705
DO - 10.1016/j.biopha.2022.112705
M3 - Article
C2 - 35168074
AN - SCOPUS:85124379696
SN - 0753-3322
VL - 148
JO - Biomedicine and Pharmacotherapy
JF - Biomedicine and Pharmacotherapy
M1 - 112705
ER -