ArticleToxicological sciences : an official journal of the Society of Toxicology2015
Airway tissue plasminogen activator prevents acute mortality due to lethal sulfur mustard inhalation.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Meta-Analysis of Preclinical Studies of Fibrinolytic Therapy for Acute Lung Injury.Frontiers in immunology · 2018Pooled it
- Establishment of a Mouse Model ofMicroorganisms · 2024Article
- TLR4 Ligation by eNAMPT, a Novel DAMP, is Essential to Sulfur Mustard- Induced Inflammatory Lung Injury and Fibrosis.European journal of respiratory medicine · 2024Article
- Mesna Improves Outcomes of Sulfur Mustard Inhalation Toxicity in an Acute Rat Model.The Journal of pharmacology and experimental therapeutics · 2024Article
- Possible Treatment Approaches of Sulfur Mustard-Induced Lung Disorders, Experimental and Clinical Evidence, an Updated Review.Frontiers in medicine · 2022Review
- Assessment of Beta-2 Microglobulin Gene Edited Airway Epithelial Stem Cells as a treatment for Sulfur Mustard Inhalation.Frontiers in genome editing · 2022Article
- Acute cytotoxicity and increased vascular endothelial growth factor after in vitro nitrogen mustard vapor exposure.Annals of the New York Academy of Sciences · 2020Article
- Alleviation of methyl isocyanate-induced airway obstruction and mortality by tissue plasminogen activator.Annals of the New York Academy of Sciences · 2020Article
- Fibrinolytic therapy for refractory COVID-19 acute respiratory distress syndrome: Scientific rationale and review.Research and practice in thrombosis and haemostasis · 2020Review
- Supporting Fundamental Chemical Toxicology Research To Inform Medical Countermeasure Developments: The National Institutes of Health Chemical Countermeasures Research Program.Chemical research in toxicology · 2020Article
- Long-term Respiratory Effects of Mustard Vesicants.Toxicology letters · 2020Review
- Automated 3D segmentation of methyl isocyanate-exposed rat trachea using an ultra-thin, fully fiber optic optical coherence endoscopic probe.Scientific reports · 2018Article
- Bronchiolitis Obliterans and Pulmonary Fibrosis after Sulfur Mustard Inhalation in Rats.American journal of respiratory cell and molecular biology · 2018Article
- Oxygen Administration Improves Survival but Worsens Cardiopulmonary Functions in Chlorine-exposed Rats.American journal of respiratory cell and molecular biology · 2018Article
- Targeting plasminogen activator inhibitor-1 in tetracycline-induced pleural injury in rabbits.American journal of physiology. Lung cellular and molecular physiology · 2018Article
- Editor's Highlight: Pulmonary Vascular Thrombosis in Rats Exposed to Inhaled Sulfur Mustard.Toxicological sciences : an official journal of the Society of Toxicology · 2017Article
- An Official American Thoracic Society Workshop Report: Chemical Inhalational Disasters. Biology of Lung Injury, Development of Novel Therapeutics, and Medical Preparedness.Annals of the American Thoracic Society · 2017Article
- Acute lung injury and persistent small airway disease in a rabbit model of chlorine inhalation.Toxicology and applied pharmacology · 2017Article
- From the Cover: Catalytic Antioxidant Rescue of Inhaled Sulfur Mustard Toxicity.Toxicological sciences : an official journal of the Society of Toxicology · 2016Article
- Mustard vesicant-induced lung injury: Advances in therapy.Toxicology and applied pharmacology · 2016Review
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
rationaleSulfur mustard (SM) is a chemical weapon stockpiled today in volatile regions of the world. SM inhalation causes a life-threatening airway injury characterized by airway obstruction from fibrin casts, which can lead to respiratory failure and death. Mortality in those requiring intubation is more than 80%. No therapy exists to prevent mortality after SM exposure. Our previous work using the less toxic analog of SM, 2-chloroethyl ethyl sulfide, identified tissue plasminogen activator (tPA) an effective rescue therapy for airway cast obstruction (Veress, L. A., Hendry-Hofer, T. B., Loader, J. E., Rioux, J. S., Garlick, R. B., and White, C. W. (2013). Tissue plasminogen activator prevents mortality from sulfur mustard analog-induced airway obstruction. Am. J. Respir. Cell Mol. Biol. 48, 439-447). It is not known if exposure to neat SM vapor, the primary agent used in chemical warfare, will also cause death due to airway casts, and if tPA could be used to improve outcome.
methodsAdult rats were exposed to SM, and when oxygen saturation reached less than 85% (median: 6.5 h), intratracheal tPA or placebo was given under isoflurane anesthesia every 4 h for 48 h. Oxygen saturation, clinical distress, and arterial blood gases were assessed. Microdissection was done to assess airway obstruction by casts.
resultsIntratracheal tPA treatment eliminated mortality (0% at 48 h) and greatly improved morbidity after lethal SM inhalation (100% death in controls). tPA normalized SM-associated hypoxemia, hypercarbia, and lactic acidosis, and improved respiratory distress. Moreover, tPA treatment resulted in greatly diminished airway casts, preventing respiratory failure from airway obstruction.
conclusionstPA given via airway more than 6 h after exposure prevented death from lethal SM inhalation, and normalized oxygenation and ventilation defects, thereby rescuing from respiratory distress and failure. Intra-airway tPA should be considered as a life-saving rescue therapy after a significant SM inhalation exposure incident.
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Registered trials
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