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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Bibliographic Details
Published in:PloS one 2021-10, Vol.16 (10), p.e0258368-e0258368
Main Authors: Michaelsen, Vinicius S, Ribeiro, Rafaela V P, Brambate, Edson, Ali, Aadil, Wang, Aizhou, Pires, Layla, Kawashima, Mitsuaki, Zhang, Yu, Gazzalle, Anajara, Keshavjee, Shaf, Del Sorbo, Lorenzo, Cypel, Marcelo
Format: Article
Language:English
Subjects:
Administration, Inhalation
Animal models
Animals
Anti-infective agents
Anti-Infective Agents - administration & dosage
Antiinfectives and antibacterials
Antimicrobial agents
Biochemistry
Biology and Life Sciences
By products
Clinical trials
Complications and side effects
Coronaviruses
Cytokines
Cytokines - analysis
Cytokines - blood
Drug Evaluation, Preclinical
Evaluation
Extubation
Feasibility
Gas exchange
Health care networks
Hemodynamics
Hemoglobin A - analysis
Histology
Infections
Inflammation
Intravenous administration
Laboratory animals
Lung - metabolism
Lung - pathology
Lungs
Male
Markers
Mechanical ventilation
Medicine and Health Sciences
Methemoglobin - analysis
Methylene blue
Methylene Blue - administration & dosage
Microorganisms
Models, Animal
Nitrates - analysis
Nitric oxide
Nitric Oxide - administration & dosage
Nitrites - analysis
Nitrogen dioxide
Ostomy
Patient outcomes
Physical Sciences
Respiratory function
Respiratory tract
Respiratory tract diseases
Safety
Severe acute respiratory syndrome coronavirus 2
Swine
Tissue analysis
Ventilation
Ventilators
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Summary: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
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0258368