Chronological Changes in Electrolyte Levels in Arterial Blood and Bronchoalveolar Lavage Fluid in Mice After Exposure to an Edemagenic Gas

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/m 3 (8-11 ppm) phosgene for 20 min (640-840 mg·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 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 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 ≤ .03 and p ≤ .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 ≤ .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 ≤ .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 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.