A novel pre-clinical strategy to deliver antimicrobial doses of inhaled nitric oxide.
Effective treatment of respiratory infections continues to be a major challenge. In high doses (≥160 ppm), inhaled Nitric Oxide (iNO) has been shown to act as a broad-spectrum antimicrobial agent, including its efficacy in vitro for coronavirus family. However, the safety of prolonged in vivo implem...
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2021
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oai:doaj.org-article:be25913353d349a8a8fe74aa6e41fd902021-12-02T20:07:55ZA novel pre-clinical strategy to deliver antimicrobial doses of inhaled nitric oxide.1932-620310.1371/journal.pone.0258368https://doaj.org/article/be25913353d349a8a8fe74aa6e41fd902021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0258368https://doaj.org/toc/1932-6203Effective treatment of respiratory infections continues to be a major challenge. In high doses (≥160 ppm), inhaled Nitric Oxide (iNO) has been shown to act as a broad-spectrum antimicrobial agent, including its efficacy in vitro for coronavirus family. However, the safety of prolonged in vivo implementation of high-dose iNO therapy has not been studied. Herein we aim to explore the feasibility and safety of delivering continuous high-dose iNO over an extended period of time using an in vivo animal model. Yorkshire pigs were randomized to one of the following two groups: group 1, standard ventilation; and group 2, standard ventilation + continuous iNO 160 ppm + methylene blue (MB) as intravenous bolus, whenever required, to maintain metHb <6%. Both groups were ventilated continuously for 6 hours, then the animals were weaned from sedation, mechanical ventilation and followed for 3 days. During treatment, and on the third post-operative day, physiologic assessments were performed to monitor lung function and other significative markers were assessed for potential pulmonary or systemic injury. No significant change in lung function, or inflammatory markers were observed during the study period. Both gas exchange function, lung tissue cytokine analysis and histology were similar between treated and control animals. During treatment, levels of metHb were maintained <6% by administration of MB, and NO2 remained <5 ppm. Additionally, considering extrapulmonary effects, no significant changes were observed in biochemistry markers. Our findings showed that high-dose iNO delivered continuously over 6 hours with adjuvant MB is clinically feasible and safe. These findings support the development of investigations of continuous high-dose iNO treatment of respiratory tract infections, including SARS-CoV-2.Vinicius S MichaelsenRafaela V P RibeiroEdson BrambateAadil AliAizhou WangLayla PiresMitsuaki KawashimaYu ZhangAnajara GazzalleShaf KeshavjeeLorenzo Del SorboMarcelo CypelPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 10, p e0258368 (2021) |
| institution |
DOAJ |
| collection |
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| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Vinicius S Michaelsen Rafaela V P Ribeiro Edson Brambate Aadil Ali Aizhou Wang Layla Pires Mitsuaki Kawashima Yu Zhang Anajara Gazzalle Shaf Keshavjee Lorenzo Del Sorbo Marcelo Cypel A novel pre-clinical strategy to deliver antimicrobial doses of inhaled nitric oxide. |
| description |
Effective treatment of respiratory infections continues to be a major challenge. In high doses (≥160 ppm), inhaled Nitric Oxide (iNO) has been shown to act as a broad-spectrum antimicrobial agent, including its efficacy in vitro for coronavirus family. However, the safety of prolonged in vivo implementation of high-dose iNO therapy has not been studied. Herein we aim to explore the feasibility and safety of delivering continuous high-dose iNO over an extended period of time using an in vivo animal model. Yorkshire pigs were randomized to one of the following two groups: group 1, standard ventilation; and group 2, standard ventilation + continuous iNO 160 ppm + methylene blue (MB) as intravenous bolus, whenever required, to maintain metHb <6%. Both groups were ventilated continuously for 6 hours, then the animals were weaned from sedation, mechanical ventilation and followed for 3 days. During treatment, and on the third post-operative day, physiologic assessments were performed to monitor lung function and other significative markers were assessed for potential pulmonary or systemic injury. No significant change in lung function, or inflammatory markers were observed during the study period. Both gas exchange function, lung tissue cytokine analysis and histology were similar between treated and control animals. During treatment, levels of metHb were maintained <6% by administration of MB, and NO2 remained <5 ppm. Additionally, considering extrapulmonary effects, no significant changes were observed in biochemistry markers. Our findings showed that high-dose iNO delivered continuously over 6 hours with adjuvant MB is clinically feasible and safe. These findings support the development of investigations of continuous high-dose iNO treatment of respiratory tract infections, including SARS-CoV-2. |
| format |
article |
| author |
Vinicius S Michaelsen Rafaela V P Ribeiro Edson Brambate Aadil Ali Aizhou Wang Layla Pires Mitsuaki Kawashima Yu Zhang Anajara Gazzalle Shaf Keshavjee Lorenzo Del Sorbo Marcelo Cypel |
| author_facet |
Vinicius S Michaelsen Rafaela V P Ribeiro Edson Brambate Aadil Ali Aizhou Wang Layla Pires Mitsuaki Kawashima Yu Zhang Anajara Gazzalle Shaf Keshavjee Lorenzo Del Sorbo Marcelo Cypel |
| author_sort |
Vinicius S Michaelsen |
| title |
A novel pre-clinical strategy to deliver antimicrobial doses of inhaled nitric oxide. |
| title_short |
A novel pre-clinical strategy to deliver antimicrobial doses of inhaled nitric oxide. |
| title_full |
A novel pre-clinical strategy to deliver antimicrobial doses of inhaled nitric oxide. |
| title_fullStr |
A novel pre-clinical strategy to deliver antimicrobial doses of inhaled nitric oxide. |
| title_full_unstemmed |
A novel pre-clinical strategy to deliver antimicrobial doses of inhaled nitric oxide. |
| title_sort |
novel pre-clinical strategy to deliver antimicrobial doses of inhaled nitric oxide. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2021 |
| url |
https://doaj.org/article/be25913353d349a8a8fe74aa6e41fd90 |
| work_keys_str_mv |
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