Preliminary Studies of Sulphur Mustard-Induced Lung Injury in the Terminally Anesthetized Pig: Exposure System and Methodology

• Published in: Toxicology mechanisms and methods 2008-01, Vol.18 (4), p.355-362
• Main Authors: Fairhall, S. J., Brown, R. F. R., Jugg, B. J. A., Smith, A. J., Mann, T. M., Jenner, J., Sciuto, A. M.
• Format: Article
• Language: English
• Subjects: Bis(2-chloroethyl)sulphide; Endotracheal Tube; Inhalation; Lung Compliance; Lung Resistance; Methylsalicylate (MS); Minute Volume; Model Development; Pig; Porcine; Sulphur Mustard (HD) Vapor
• ISSN: 1537-6516; 1537-6524
• DOI: 10.1080/15376510701623383

ABSTRACT Although normally regarded as a vesicant, inhalation of sulphur mustard (HD) vapor can cause life-threatening lung injury for which there is no specific treatment. Novel therapies for HD-induced lung injury are best investigated in an in vivo model that allows monitoring of a range of physiological variables. HD vapor was generated using two customized thermostatically controlled glass flasks in parallel. The vapor was passed into a carrier flow of air (81 L· min−1) and down a length of glass exposure tube (1.75 m). A pig was connected to the midpoint of the exposure tube via a polytetrafluoroethylene-lined endotracheal tube, Fleisch pneumotachograph, and sample port. HD vapor concentrations (40-122.8 mg. m−3) up-and downstream of the point of exposure were obtained by sampling onto Porapak absorption tubes with subsequent analysis by gas chromatography-flame photometric detection. Real-time estimates of vapor concentration were determined using a photo-ionization detector. Lung function indices (respiratory volumes, lung compliance, and airway resistance) were measured online throughout. Trial runs with methylsalicylate (MS) and animal exposures with HD demonstrated that the exposure system rapidly reached the desired concentration within 1 min and maintained stable output throughout exposure, and that the MS/HD concentration decayed rapidly to zero when switched off. A system is described that allows reproducible exposure of HD vapor to the lung of anesthetized white pigs. The system has proved to be robust and reliable and will be a valuable tool in assessing potential future therapies against HD-induced lung injury in the pig. Crown Copyright (c) 2007 Dstl.