We studied lung clearance of
technetium-labeled
diethylenetriamine pentaacetic acid [( 99mTc]
DTPA), plasma and bronchoalveolar lavage fluid (BALF) concentrations of
6-keto-PGF1 alpha (stable metabolite of
prostacyclin,
prostaglandin I2, PGI2), TxB2 (stable metabolite of
thromboxane A2, TxA2), and
leukotriene B4 (
LTB4), and inflammatory cells as indices of
lung injury in rabbits exposed to cigarette
smoke (CSE). Thirty-one rabbits were randomly assigned to four groups: control
sham exposure (SS, n = 6),
sham smoke ibuprofen-pretreated (SS-I, n = 7), CSE (n = 6), and CSE
ibuprofen-pretreated (CSE-I, n = 12).
Ibuprofen, a
cyclooxygenase eicosanoid inhibitor, was administered as a single daily
intramuscular injection (25 mg/kg) for 7 d 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 [99mTc]
DTPA biological half-life (T1/2). The CSE-I group was retrospectively divided into rabbits who survived the 30-breath subset (CSE-IL, n = 6) and those who died during the 30-breath CSE (CSE-ID, n = 6). In the CSE, CSE-IL, and CSE-ID groups, [99mTc]
DTPA T1/2 as well as BALF
LTB4 levels were significantly decreased. Plasma and BALF
6-keto-PGF1 alpha increased in CSE rabbits compared to the other groups. Alveolar macrophages were lower in the CSE-ID rabbits than in the CSE-IL group. CSE and CSE-IL BALF lymphocyte levels were decreased compared to SS values. Our data indicate that acute CSE is associated with significant increases in
6-keto-PGF1 alpha and decreases in
LTB4 as well as a significant reduction in lymphocytes. Furthermore, pretreatment with
ibuprofen before CSE was associated with severe
lung injury in half of the rabbits. The severity of
lung injury may be related to a combination of a lower number of alveolar macrophages and blockade of lung PGI2.