Dibutyryl cAMP, aminophylline, and beta-adrenergic agonists protect against pulmonary edema caused by phosgene.
Kennedy-TP; Michael-JR; Hoidal-JR; Hasty-D; Sciuto-AM; Hopkins-C; Lazar-R; Bysani-GK; Tolley-E; Gurtner-GH
J Appl Physiol 1989 Dec; 67(6):2542-2552
A study of the effect of phosgene (75445) on rabbit lung weight gain at different levels of left atrial pressure and on the movement of iodine-125 labeled albumin from the vasculature into lung water and alveolar fluid was reported. Male New-Zealand-White-rabbits were exposed to phosgene in an exposure box at a concentration time product of 2000 parts per million/minute (ppm/min). Lungs of rabbits pretreated with dibutyryl- adenosine-3',5'- cyclicmonophosphate (DBcAMP), aminophylline, or terbutaline plus isoproterenol were studied 30 minutes after exposure. Lungs of rabbits post treated 10 minutes after exposure to 2000 or 1500ppm/min were studied 4 hours after exposure. Lungs were perfused with protein free Krebs-henseleit buffer, and ventilated with 5 percent carbon-dioxide in air. The pulmonary arterial pressure and left atrial pressure were determined; lung weight changes were recorded. Phosgene markedly increased lung weight gain in buffer perfused isolated rabbit lungs and markedly increased the lung leak index for albumin. Pretreatment with DBcAMP, aminophylline, or terbutaline plus isoproterenol prevented the increase in lung weight caused by phosgene. Pretreatment with aminophylline prevented the increase in lung leak index for albumin. Post treatment with aminophylline and terbutaline also prevented the increase in lung weight caused by phosgene. The results indicated that DBcAMP, aminophylline, terbutaline, and isoproterenol significantly reduced the pulmonary edema and the likely increase in pulmonary vascular permeability caused by phosgene. According to the authors, these drugs may eventually prove useful therapy for victims of phosgene inhalation if administered soon after exposure.
NIOSH-Publication; NIOSH-Grant; Laboratory-animals; Pulmonary-system-disorders; Lung-disease; Toxic-gases; Inhalation-studies; Alveolar-cells; In-vivo-studies; Cell-damage
Medicine University of Tennessee Room H-314, Coleman Bldg Memphis, TN 38163
Journal of Applied Physiology
University of Tenn Center Health Scien, Memphis, Tennessee