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Inhal Toxicol. 2003 Jun;15(7):663-74.

Chronological changes in electrolyte levels in arterial blood and bronchoalveolar lavage fluid in mice after exposure to an edemagenic gas.

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Neurotoxicology Branch, Pharmacology Division, MCMR-UV-PN, U.S. Army Medical Research Institute of Chemical Defense, 3100 Ricketts Point Rd., Aberdeen Proving Ground, MD 21010-5400, USA.


Detection of acute lung injury is important if therapeutic medical countermeasures are to be used to reduce toxicity in a timely manner. Indicators of injury may aid in the eventual treatment course and enhance the odds of a positive outcome following a toxic exposure. This study was designed to investigate the effects of a toxic exposure to the industrial irritant gas phosgene on the electrolyte levels in arterial blood and bronchoalveolar lavage fluid (BALF). Phosgene is a well-known chemical intermediate capable of producing life-threatening pulmonary edema within hours after exposure. Four groups of 40 Crl:CD-1(ICR)BR male mice were exposed whole-body to either air or phosgene at a concentration x time (c x t) amount of 32-42 mg/m(3) (8-11 ppm) phosgene for 20 min (640-840 mg x min/m(3)). BALF from air- or phosgene-exposed mice was taken at 1, 4, 8, 12, 24, 48, or 72 h postexposure. After euthanasia, the trachea was excised, and 800 microl saline was instilled into the lungs. The lungs were washed 5x. Eighty microliters of BALF was placed in a cartridge and inserted into a clinical i-STAT analyzer. Na(+), Cl(-), K(+), and ionized Ca(2+) were analyzed. Arterial blood electrolyte levels were also analyzed in four additional groups of air- or phosgene-exposed mice. The left lung was removed to determine wet weight (WW), an indicator of pulmonary edema. Na(+) was significantly higher in air than in phosgene-exposed mice at 4, 8, and 12 h postexposure. Temporal changes in BALF Cl(-) in phosgene mice were not statistically different from those in the air mice. Both Ca(2+) and K(+) were significantly higher than in the air-exposed mice over 72 h, p < or = 0.03 and p < or = 0.001 (two-way analysis of variance, ANOVA), respectively. Significant changes in BALF K(+) and Ca(2+) occurred as early as 4 h postexposure in phosgene, p < or = 0.005, versus air-exposed mice. Over time, there were no significant changes in arterial blood levels of Na(+), Cl(-), or Ca(2+) for animals exposed to air versus phosgene. However, arterial K(+) concentrations were significantly higher, p < or = 0.05, than in air-exposed mice across all time points, with the highest K(+) levels of 7 mmol/L occurring at 8 h and 24 h after exposure. Phosgene caused a time-dependent significant increase in WW from 4 to 12 h, p < or = 0.025, compared with air-exposed mice. These data demonstrate that measuring blood K(+) levels 1 h after exposure along with BALF Na(+), K(+), and Ca(2+) may serve as an alternate indicators of lung injury since both K(+) and Ca(2+) follow temporal increases in air-blood barrier permeability as measured by wet weight.

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