Am. J. Respir. Crit. Care Med., Vol 151, No. 3, 03 1995, 768-772.
Protective effects of N-acetylcysteine treatment after phosgene exposure in rabbits
AM Sciuto, PT Strickland, TP Kennedy and GH Gurtner
Department of Environmental Health Sciences, Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland.
We examined the effects of treatment with N-acetylcysteine (NAC) on
pulmonary edema formation in isolated perfused rabbit lungs following in
vivo phosgene exposure. This study focused on posttreatment intratracheal
administration of NAC after exposure. Rabbits, 2 to 3 kg, were exposed to a
cumulative dose of phosgene to attain a concentration x time exposure
effect of 1,500 ppm/min. Lungs were perfused with Krebs- Henseleit buffer
at 40 ml/min from 70 to 150 min after exposure. Pulmonary artery pressure
(Ppa), tracheal pressure (Pt), and the rate of lung weight gain (LWG) were
measured continuously. Perfusate concentration of peptide leukotrienes
LTC4, D4, and E4 were measured every 20 min during perfusion. At the
conclusion of the experiment, lung tissue was analyzed for reduced and
oxidized glutathione (GSH and GSSG) and lipid peroxidation (thiobarbituric
acid-reactive substances, TBARS). Exposure to phosgene significantly
increased Pt, LWG, LTC4, D4, and E4, TBARS, and GSSG over time compared
with controls. Compared with phosgene, intratracheal NAC lowered Ppa, LWG,
LTC4, D4, and E4, TBARS, and GSSG. We conclude that NAC protected against
phosgene-induced lung injury by acting as an antioxidant by maintaining
protective levels of glutathione, reducing both lipid peroxidation and
production of arachidonic acid metabolites.
