Piriprost pretreatment attenuates the smoke-induced increase in 99mTcDTPA lung clearance.
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.
Witten
M L
ML
Department of Physiology, University of Arizona Health Sciences Center, Tucson 85724.
Grad
R
R
Quan
S F
SF
Sobonya
R E
RE
Hubbard
A K
AK
Lantz
R C
RC
Lentz
L A
LA
Devine
L C
LC
Lemen
R J
RJ
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
D015777:Eicosanoids; D015609:Organotechnetium Compounds; D013189:SRS-A; D004369:Pentetic Acid; D011464:Epoprostenol; D010960:Plasminogen Activators; C035296:piriprost; D016284:Technetium Tc 99m Pentetate