Changes in lung ATP concentration in the rat after low‐level phosgene exposure

Abstract

Inhibition of mitochondrial respiratory activity and decreased lung adenosine triphosphate (ATP) concentration occur following exposure to 240 ppm.min phosgene. To determine the relationship between energy stores and the onset of phosgene-induced pulmonary edema, we measured the ATP concentration in rapidly frozen rat lung tissue before and during pulmonary edema. Male Sprague-Dawley rats were exposed to phosgene for four hours at concentrations of 0.05 to 1.0 ppm (12, 30, 60, 120, and 240 ppm.min). Lung wet and dry weight and ATP concentration were measured immediately after exposure and for three days postexposure. The accumulation of lavage fluid protein (LFP) was also measured as an index of damage or edema due to phosgene. Lung dry weight was significantly elevated one day postexposure to 0.5 ppm phosgene, while the LFP was elevated by 0.2 ppm phosgene. Time course studies at these doses of phosgene showed that decreased ATP levels preceded the onset of edema or increase in lung weight. The ATP values expressed on a per-lung basis showed that ATP levels were significantly lowered immediately following phosgene exposure, suggesting that the ATP changes were not the result of edema. This study is the first demonstration of a biochemical change that occurs following exposure to phosgene at a level significantly below the threshold limit value for this gas.