Dibutyryl cAMP effects on thromboxane and leukotriene production in decompression-induced lung injury.
Decompression-induced venous bubble formation has been linked to increased neutrophil counts, endothelial cell injury, release of vasoactive eicosanoids, and increased vascular membrane permeability. These actions may account for inflammatory responses and edema formation. Increasing the intracellular cAMP has been shown to decrease eicosanoid production and edema formation in various models of lung injury. Reduction of decompression-induced inflammatory responses was evaluated in decompressed rats pretreated with saline (controls) or dibutyryl cAMP (DBcAMP, an analog of cAMP). After pretreatment, rats were exposed to either 616 kPa for 120 min or 683 kPa for 60 min. The observed increases in extravascular lung water ratios (pulmonary edema), bronchoalveolar lavage, and pleural protein in the saline control group (683 kPa) were not evident with DBcAMP treatment. DBcAMP pretreatment effects were also seen with the white blood cell counts and the percent of neutrophils in the bronchoalveolar lavage. Urinary levels of thromboxane B2, 11-dehydrothromboxane B2, and leukotriene E4 were significantly increased with the 683 kPa saline control decompression exposure. DBcAMP reduced the decompression-induced leukotriene E4 production in the urine. Plasma levels of thromboxane B2, 11-dehydrothromboxane B2, and leukotriene E4 were increased with the 683-kPa exposure groups. DBcAMP treatment did not affect these changes. The 11-dehydrothromboxane B2 and leukotriene E4 levels in the bronchoalveolar lavage were increased with the 683 kPa exposure and were reduced with the DBcAMP treatment. Our results indicate that DBcAMP has the capability to reduce eicosanoid production and limit membrane permeability and subsequent edema formation in rats experiencing decompression sickness.
Little
T M
TM
Department of Anesthesiology, University of Texas Medical School, Houston 77030, USA.
Butler
B D
BD
D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D003994:Bucladesine / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects; D003665:Decompression Sickness / Q000097:blood* / Q000652:urine; D007958:Leukocyte Count; D017999:Leukotriene E4 / Q000097:blood* / Q000652:urine; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D009929:Organ Size; D011654:Pulmonary Edema / Q000097:blood / Q000473:pathology / Q000517:prevention & control / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D013929:Thromboxane B2 / Q000031:analogs & derivatives* / Q000097:blood* / Q000652:urine
D015415:Biomarkers; D013929:Thromboxane B2; D003994:Bucladesine; C049235:11-dehydro-thromboxane B2; D017999:Leukotriene E4