One hallmark of
phosgene inhalation toxicity is the latent formation of life-threatening, noncardiogenic
pulmonary edema. The purpose of this study was to investigate the effect of
phosgene inhalation on respiratory dynamics over 12 h. CD-1 male mice, 25-30 g, were exposed to 32 mg/m(3) (8 ppm)
phosgene for 20 min (640 mg min/m(3)) followed by a 5-min air washout. A similar group of mice was exposed to room air for 25 min. After exposure, conscious mice were placed unrestrained in a whole-body plethysmograph to determine breathing frequency (f), inspiration (Ti) and expiration (Te) times, tidal volume (TV), minute ventilation (MV), end inspiratory pause (EIP), end expiratory (EEP) pause, peak inspiratory flows (PIF), peak expiratory flows (PEF), and a measure of bronchoconstriction (Penh). All parameters were evaluated every 15 min for 12 h. Bronchoalveolar lavage fluid (BALF)
protein concentration and
lung wet/dry weight ratios (W/D) were also determined at 1, 4, 8, and 12 h. A treatment x time repeated-measures two-way analysis of variance (ANOVA) revealed significant differences between air and
phosgene for EEP, EIP, PEF, PIF, TV, and MV, p < or =.05, across 12 h.
Phosgene-exposed mice had a significantly longer mean Ti, p < or =.05, compared with air-exposed mice over time. Mice exposed to
phosgene showed marked increases (approximately double) in Penh across all time points, beginning at 5 h, when compared with air-exposed mice, p < or =.05. BALF
protein, an
indicator of air/blood barrier integrity, and W/D were significantly higher, 10- to 12-fold, in
phosgene-exposed than in air-exposed mice 4-12 h after exposure, p <or =.001 and p < or =.05, respectively. These results indicate that exposure to
phosgene causes early bronchoconstriction, a temporal obstructivelike injury pattern, and disruption of mechanical rhythm largely regulated by the progressive production of
pulmonary edema on airway flow. Potential therapeutic intervention may include compounds that produce bronchodilation and
mechanical ventilation support if warranted.