Acute cigarette smoke exposure causes lung injury in rabbits treated with ibuprofen.
We studied lung clearance of aerosolized technetium-labeled diethylenetriamine pentaacetic acid (99mTcDTPA), plasma concentrations of 6-keto-PGF1 alpha and thromboxane B2, and pulmonary edema as indices of lung injury in rabbits exposed to cigarette smoke (CSE). Forty-six rabbits were randomly assigned to 4 groups: control sham smoke exposure (SS, N = 9), sham smoke exposure ibuprofen-pretreated (SS-I, N = 10), CSE (N = 9), sham smoke exposure ibuprofen-pretreated (SS-I, N = 10), CSE (N = 9), and CSE ibuprofen-pretreated (CSE-I, N = 19). Ibuprofen (cyclooxygenase eicosanoid inhibitor) was administered as a single daily intramuscular injection (25 mg/kg) for 7 days before the experiment. Cigarette or sham smoke was delivered by syringe in a series of 5, 10, 20, and 30 tidal volume breaths with a 15-min counting period between each subset of breaths to determine 99mTcDTPA biological half-life (T1/2). In the ibuprofen pretreated group, CSE caused significant decreases in 99mTcDTPA T1/2 and dynamic lung compliance. Furthermore, these changes in lung function were accompanied by severe injury to type I alveolar cell epithelium, pulmonary edema, and frequently death of the rabbits. These findings suggest that inhibition of the cyclooxygenase pathway before CSE exacerbates lung injury in rabbits.
Witten
M L
ML
Department of Physiology, University of Arizona College of Medicine, Tucson 85724.
Lemen
R J
RJ
Quan
S F
SF
Sobonya
R E
RE
Magarelli
J L
JL
Bruck
D C
DC
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D005260:Female; D007052:Ibuprofen / Q000494:pharmacology*; D008168:Lung / Q000473:pathology / Q000648:ultrastructure; D008171:Lung Diseases / Q000209:etiology*; D008297:Male; D009942:Organometallic Compounds / Q000493:pharmacokinetics; D004369:Pentetic Acid / Q000493:pharmacokinetics; D010947:Plants, Toxic; D011650:Pulmonary Alveoli / Q000378:metabolism; D011654:Pulmonary Edema / Q000473:pathology; D011817:Rabbits; D012906:Smoke / Q000009:adverse effects*; D013667:Technetium / Q000493:pharmacokinetics; D016284:Technetium Tc 99m Pentetate; D013929:Thromboxane B2 / Q000097:blood; D013997:Time Factors; D014026:Nicotiana
D009942:Organometallic Compounds; D012906:Smoke; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D013667:Technetium; D004369:Pentetic Acid; D016284:Technetium Tc 99m Pentetate; D007052:Ibuprofen