Gm. Cleary et al., EXUDATIVE LUNG INJURY IS ASSOCIATED WITH DECREASED LEVELS OF SURFACTANT PROTEINS IN A RAT MODEL OF MECONIUM ASPIRATION, Pediatrics, 100(6), 1997, pp. 998-1003
Objective. Meconium aspiration syndrome remains a common cause of resp
iratory failure in neonates. The acute effects of meconium aspiration
are inactivation of lung surfactant in vivo and in vitro. This study i
nvestigated the delayed effects of meconium on alveolar surfactant pho
spholipids and protein levels in spontaneously breathing animals. Meth
ods. Twenty-two adult rats were given 4.3 mg of dry weight human mecon
ium after endotracheal intubation. Rats were briefly mechanically vent
ilated in room air, extubated, then killed after 16 (n = 6), 24 (n = 6
), 48 (n = 6), and 72 hours (n = 4). Control animals received the same
volume of normal saline (n = 7) or no meconiun (n = 7). Bronchoalveol
ar lavage and tissue specimens were evaluated for inflammatory cells,
total proteins, surfactant phospholipids, and surfactant proteins. Res
ults. Meconium caused exudative lung injury that was reflected in incr
eased cell counts and proteins in alveolar lavage fluid. The peak inju
ry occurred at 16 hours after instillation, whereas recovery occurred
by 72 hours. Although total lavage fluid phospholipids did not change
over time, phospholipid and dipalmitoyl phosphatidylcholine in large a
ggregates tended to decrease at 24 hours. Western blot analysis demons
trated time-dependent qualitative decreases in surfactant proteins A a
nd B (SP-A, SP-B) in meconium-instilled animals compared with the cont
rols. ELISA for SP-B confirmed the Western blot findings with total SP
-B in large aggregate decreasing from 25 +/- 4 mu g in controls to 6.6
+/- 0.8 mu g at 24 hours of injury. Conclusions. Our study suggests t
hat the exudative lung injury with meconium instillation is associated
with decreased levels of SP-A and SP-B in the large aggregate fractio
n of lung surfactant. We speculate that decreased secretion and/or inc
reased degradation accounts for lower levels of SP-B in bronchoalveola
r lavage fluid.