Alleviation of methyl isocyanate-induced airway obstruction and mortality by tissue plasminogen activator
| Autor: | Leslie A. Bloomquist, William Sosna, Eric Peters, Livia A. Veress, Carl W. White, Richard S. Tuttle, Poojya Anantharam, Claire R. Croutch, Heidi J. Nick, Jacqueline S. Rioux, Preston E. Bratcher |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Pharmacology Methyl isocyanate Tissue plasminogen activator General Biochemistry Genetics and Molecular Biology Article Hypoxemia Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine History and Philosophy of Science medicine Animals 030304 developmental biology 0303 health sciences Inhalation Respiratory distress business.industry General Neuroscience Airway obstruction medicine.disease Rats Airway Obstruction Disease Models Animal 030228 respiratory system Respiratory failure chemistry Tissue Plasminogen Activator medicine.symptom business Fibrinolytic agent medicine.drug Isocyanates |
| Zdroj: | Ann N Y Acad Sci |
| ISSN: | 1749-6632 |
| Popis: | Methyl isocyanate (MIC, “Bhopal agent”) is a highly reactive, toxic industrial chemical. Inhalation of high levels (500–1000 ppm) of MIC vapor are almost uniformly fatal. No therapeutic interventions other than supportive care have been described that can delay the onset of illness or death owing to MIC. Recently, we found that inhalation of MIC caused the appearance of activated tissue factor in circulation with subsequent activation of the coagulation cascade. Herein we report that MIC exposure (500 ppm for 30 min, nose-only) caused deposition of fibrin-rich casts in the conducting airways resulting in respiratory failure and death within 24 h in a rat model (LC(90−100)). We thus investigated the effect of airway delivery of the fibrinolytic agent tissue plasminogen activator (tPA) on mortality and morbidity in this model. Intratracheal administration of tPA was initiated 11 h post-MIC exposure and repeated every 4 h for the duration of the study. Treatment with tPA afforded nearly 60% survival at 24 h post-MIC exposure and was associated with decreased airway fibrin casts, stabilization of hypoxemia and respiratory distress, and improved acidosis. This work supports the potential of airway-delivered tPA therapy as a useful countermeasure in stabilizing victims of high-level MIC exposure. |
| Databáze: | OpenAIRE |
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