{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,20]],"date-time":"2025-09-20T21:57:38Z","timestamp":1758405458853},"reference-count":56,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,3,31]],"date-time":"2020-03-31T00:00:00Z","timestamp":1585612800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["nyaspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of the New York Academy of Sciences"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Methyl isocyanate (MIC, \u201cBhopal agent\u201d) is a highly reactive, toxic industrial chemical. Inhalation of high levels (500\u20131000 ppm) of MIC vapor is almost uniformly fatal. No therapeutic interventions other than supportive care have been described that can delay the onset of illness or death due 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\u2010only) caused deposition of fibrin\u2010rich casts in the conducting airways resulting in respiratory failure and death within 24 h in a rat model (LC<jats:sub>90\u2212100<\/jats:sub>). 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\u2010delivered tPA therapy as a useful countermeasure in stabilizing victims of high\u2010level MIC exposure.<\/jats:p>","DOI":"10.1111\/nyas.14344","type":"journal-article","created":{"date-parts":[[2020,3,31]],"date-time":"2020-03-31T19:50:16Z","timestamp":1585684216000},"page":"134-147","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Alleviation of methyl isocyanate\u2212induced airway obstruction and mortality by tissue plasminogen activator"],"prefix":"10.1111","volume":"1479","author":[{"given":"Heidi J.","family":"Nick","sequence":"first","affiliation":[{"name":"Department of Pediatrics University of Colorado Anschutz Medical Campus  Aurora Colorado"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacqueline S.","family":"Rioux","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Colorado Anschutz Medical Campus  Aurora Colorado"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Livia A.","family":"Veress","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Colorado Anschutz Medical Campus  Aurora Colorado"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Preston E.","family":"Bratcher","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Colorado Anschutz Medical Campus  Aurora Colorado"},{"name":"Division of Cell Biology, Department of Pediatrics National Jewish Health  Denver Colorado"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leslie A.","family":"Bloomquist","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Colorado Anschutz Medical Campus  Aurora Colorado"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Poojya","family":"Anantharam","sequence":"additional","affiliation":[{"name":"MRIGlobal  Kansas City Missouri"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claire R.","family":"Croutch","sequence":"additional","affiliation":[{"name":"MRIGlobal  Kansas City Missouri"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard S.","family":"Tuttle","sequence":"additional","affiliation":[{"name":"MRIGlobal  Kansas City Missouri"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Peters","sequence":"additional","affiliation":[{"name":"MRIGlobal  Kansas City Missouri"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"Sosna","sequence":"additional","affiliation":[{"name":"MRIGlobal  Kansas City Missouri"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carl W.","family":"White","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Colorado Anschutz Medical Campus  Aurora Colorado"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,3,31]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajem.2007.12.006"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/09603123.2017.1342226"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra030370"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1990.03450210081037"},{"key":"e_1_2_9_6_1","first-page":"435","article-title":"Comparison of two Lagrangian dispersion models: a case study for the chemical accident in Rouen, January 21\u201322, 2013","volume":"117","author":"Leelossy A.","year":"2013","journal-title":"Q. 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