Chronological Changes in Electrolyte Levels in Arterial Blood and Bronchoalveolar Lavage Fluid in Mice After Exposure to an Edemagenic Gas
Authors: Sciuto, Alfred M.; Carpin, Laura B.; Moran, Ted S.; Forster, Jeffry S.
Source: Inhalation Toxicology, Volume 15, Number 7, Jun 2003 , pp. 663-674(12)
Publisher: Informa Healthcare
Abstract: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 × time (c × t) amount of 32-42 mg/m3 (8-11 ppm) phosgene for 20 min (640-840 mg⋅min/m3). 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 µl saline was instilled into the lungs. The lungs were washed 5×. Eighty microliters of BALF was placed in a cartridge and inserted into a clinical i-STAT analyzer. Na+, Cl-, K+, and ionized Ca2+ 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 Ca2+ and K+ were significantly higher than in the air-exposed mice over 72 h, p .03 and p .001 (two-way analysis of variance, ANOVA), respectively. Significant changes in BALF K+ and Ca2+ occurred as early as 4 h postexposure in phosgene, p .005, versus air-exposed mice. Over time, there were no significant changes in arterial blood levels of Na+, Cl-, or Ca2+ for animals exposed to air versus phosgene. However, arterial K+ concentrations were significantly higher, p .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 .025, compared with air-exposed mice. These data demonstrate that measuring blood K+ levels 1 h after exposure along with BALF Na+, K+, and Ca2+ may serve as an alternate indicators of lung injury since both K+ and Ca2+ follow temporal increases in air-blood barrier permeability as measured by wet weight.
Document Type: Research Article
Affiliations: Neurotoxicology Branch, Pharmacology Division, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland, USA
Publication date: June 1, 2003