Dibutyryl cAMP, aminophylline, and beta-adrenergic agonists protect against pulmonary edema caused by phosgene

Abstract

Phosgene is a toxic oxidant gas that causes the adult respiratory distress syndrome in exposed workers. Phosgene exposure markedly increased lung weight gain in buffer-perfused isolated rabbit lungs (31 +/- 5 g over 60 min after phosgene vs. 7.7 +/- 1.2 in control lungs, P less than 0.01) and markedly increased the lung leak index for 125I-albumin (0.28 +/- 0.03 after phosgene vs. 0.02 +/- 0.01 in control lungs, P less than 0.01). Pretreatment with dibutyryl adenosine 3',5' -cyclic monophosphate (DBcAMP), aminophylline, or terbutaline plus isoproterenol prevented the increase in lung weight caused by phosgene (31 +/- 5 g phosgene, 11.7 +/- 2.8 DBcAMP, 7.5 +/- 2.5 aminophylline, 6.1 +/- 1 terbutaline and isoproterenol, 6.1 +/- 1.2 control + aminophylline, and 7.7 +/- 1.2 control; all treatments were P less than 0.01 vs. the untreated phosgene group and not significantly different from control lungs). Pretreatment with aminophylline prevented the increase in lung leak index for 125I-albumin (0.28 +/- 0.03 after phosgene vs. 0.06 +/- 0.02 in aminophylline-treated lungs, P less than 0.01). Posttreatment with aminophylline and terbutaline also prevented the increase in lung weight caused by phosgene. These results indicate that phosgene dramatically increases the movement of fluid and protein across the pulmonary vasculature and that treatment with DBcAMP, aminophylline, terbutaline, or isoproterenol markedly reduces the pulmonary edema caused by phosgene.

Pseudomonas aeruginosa exotoxin A induces pulmonary endothelial cytotoxicity: protection by dibutyryl-cAMP

“…Db-cAMP has been demonstrated to attenuate lung injury from a number of injurious stimuli [17][18][19][20][21]. However, the mechanism of protection in these instances is not known, although there is evidence that in some in vivo models it may exert a beneficial response by reducing pulmonary vascular pressures [19,20].…”

“…However, the mechanism of protection in these instances is not known, although there is evidence that in some in vivo models it may exert a beneficial response by reducing pulmonary vascular pressures [19,20]. However, there is also evidence that this protection may be related to decreasing endothelial permeability [20,21]. A further hypothesis to explain the protective influence of Db-cAMP on pulmonary endothelial cell injury is that Db-cAMP may exert its in vitro protective influence by activating protein kinase A and promoting endothelial cell membrane stability [22].…”

Defining the Phosphodiesterase Superfamily Members in Rat Brain Microvessels

“…8À10 Conversely, agents that increase endothelial cAMP levels prevent barrier injury in the lung injury models. 11,12 Evidence from other organs, such as kidney, suggests PDE involvement in osmotic water permeability. PDE function underlies arginine vasopressin-regulated water reabsorption in the principal cells of the renal collecting duct by terminating protein kinase A (PKA) signaling through hydrolysis of localized cAMP.…”

Pulmonary Structural and Extracellular Matrix Alterations in Fischer 344 Rats Following Subchronic Phosgene Exposure

“…Likewise, emissions from industrial facilities may pose episodic risks to the public living nearby (Davis et al, 1989). The acute toxicity of phosgene has been reported to, involve oxidative tissue damage and pulmonary edema due to increased vascular permeability (Franch and Hatch, 1986;Kennedy et al, 1989), which may involve arachidonic acid metabolites (Guo et al, 1990). Exposure to phosgene is also known to induce pulmonary inflammation in rats (Currie et al, 1987).…”