title: Exposure-response effects of inhaled sulfur mustard in a large porcine model: a 6-h study.
abstract: BACKGROUND
  Inhalation of sulfur mustard (HD) vapor can cause life-threatening lung injury for which there is no specific treatment. A reproducible, characterized in vivo model is required to investigate novel therapies targeting HD-induced lung injury.
  
  
  METHODS
  Anesthetized, spontaneously breathing large white pigs (~50 kg) were exposed directly to the lung to HD vapor at 60, 100, or 150 µg/kg, or to air, for ~10 min, and monitored for 6 h. Cardiovascular and respiratory parameters were recorded. Blood and bronchoalveolar lavage fluid (BALF) were collected to allow blood gas analysis, hematology, and to assay for lung inflammatory cells and mediators. Urine was collected and analyzed for HD metabolites. Histopathology samples were taken postmortem (PM).
  
  
  RESULTS
  Air-exposed animals maintained normal lung physiology whilst lying supine and spontaneously breathing. There was a statistically significant increase in shunt fraction across all three HD-exposed groups when compared with air controls at 3-6 h post-exposure. Animals were increasingly hypoxemic with respiratory acidosis. The monosulfoxide β-lyase metabolite of HD (1-methylsulfinyl-2-[2(methylthio)ethylsulfonyl)ethane], MSMTESE), was detected in urine from 2 h post-exposure. Pathological examination revealed necrosis and erosion of the tracheal epithelium in medium and high HD-exposed groups.
  
  
  CONCLUSIONS
  These findings are consistent with those seen in the early stages of acute lung injury (ALI).
authors.affiliation: Dstl Porton Down, Salisbury, UK. sjfairhall@dstl.gov.uk
authors.forename: S J
authors.initials: SJ
authors.lastname: Fairhall
authors.forename: B J A
authors.initials: BJ
authors.lastname: Jugg
authors.forename: R W
authors.initials: RW
authors.lastname: Read
authors.forename: S J
authors.initials: SJ
authors.lastname: Stubbs
authors.forename: S J
authors.initials: SJ
authors.lastname: Rutter
authors.forename: A J
authors.initials: AJ
authors.lastname: Smith
authors.forename: T M
authors.initials: TM
authors.lastname: Mann
authors.forename: J
authors.initials: J
authors.lastname: Jenner
authors.forename: A M
authors.initials: AM
authors.lastname: Sciuto
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000473:pathology; D000367:Age Factors; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D019570:Inhalation Exposure / Q000009:adverse effects*; D009151:Mustard Gas / Q000008:administration & dosage* / Q000378:metabolism / Q000633:toxicity*; D010108:Oxyhemoglobins / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects / Q000473:pathology; D013552:Swine; D013997:Time Factors
chemical_list: D010108:Oxyhemoglobins; D009151:Mustard Gas