title: Piriprost pretreatment attenuates the smoke-induced increase in 99mTcDTPA lung clearance.
abstract: We studied the effects of acute smoke exposure on lung permeability, eicosanoids, and inflammatory cell activity. Thirty-five New Zealand white rabbits were anesthetized, paralyzed, and exposed to 60 tidal volume breaths of diesel fuel-polycarbonate plastic smoke or sham smoke within 10 min. At 1 h postexposure the rabbits were killed and their lungs were removed for bronchoalveolar lavage (BAL) or pathologic procedures. Smoke exposure caused decreases in technetium-labeled diethylenetriamine pentaacetate (99mTcDTPA, mol. wt. 492 Da) biological half-life (t1/2), BAL plasminogen activator, and BAL leukotriene B4 (LTB4). In addition, alveolar macrophage acid phosphatase enzyme activity increased in smoke-exposed rabbits. The leukotriene synthesis inhibitor, piriprost (U-60,257), given before smoke exposure, caused attenuation of the changes in 99mTcDTPA uptake and plasminogen activator, swelling of type I alveolar cell epithelium, a large increase in lung inflammatory cells, and decreases in BAL LTB4, prostaglandin E2 (PGE2), and TxB2 (stable metabolite of thromboxane, TxA2). We conclude that changes in alveolar-capillary barrier permeability and plasminogen activator activity occur within 1 h after exposure to smoke and may play an early role in the inflammatory process associated with smoke inhalation injury. Furthermore, piriprost attenuates the smoke-induced increase in alveolar-capillary barrier permeability and decrease in plasminogen activator activity and causes a swelling of type I alveolar epithelium. However, our data suggest that neither lung eicosanoids or the alveolar macrophage lysis process plays a major role in the smoke-induced increase in alveolar-capillary barrier permeability.
authors.affiliation: Department of Physiology, University of Arizona Health Sciences Center, Tucson 85724.
authors.forename: M L
authors.initials: ML
authors.lastname: Witten
authors.forename: R
authors.initials: R
authors.lastname: Grad
authors.forename: S F
authors.initials: SF
authors.lastname: Quan
authors.forename: R E
authors.initials: RE
authors.lastname: Sobonya
authors.forename: A K
authors.initials: AK
authors.lastname: Hubbard
authors.forename: R C
authors.initials: RC
authors.lastname: Lantz
authors.forename: L A
authors.initials: LA
authors.lastname: Lentz
authors.forename: L C
authors.initials: LC
authors.lastname: Devine
authors.forename: R J
authors.initials: RJ
authors.lastname: Lemen
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000378:metabolism / Q000473:pathology; D015777:Eicosanoids / Q000378:metabolism; D011464:Epoprostenol / Q000494:pharmacology* / Q000031:analogs & derivatives; D006207:Half-Life; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D055370:Lung Injury; D008264:Macrophages / Q000473:pathology; D015609:Organotechnetium Compounds; D004369:Pentetic Acid; D010539:Permeability; D010960:Plasminogen Activators / Q000378:metabolism; D011817:Rabbits; D013189:SRS-A / Q000037:antagonists & inhibitors; D015208:Smoke Inhalation Injury / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D016284:Technetium Tc 99m Pentetate
chemical_list: D015777:Eicosanoids; D015609:Organotechnetium Compounds; D013189:SRS-A; D004369:Pentetic Acid; D011464:Epoprostenol; D010960:Plasminogen Activators; C035296:piriprost; D016284:Technetium Tc 99m Pentetate