Am. J. Respir. Cell Mol. Biol.,
Volume 20, Number 3, March, 1999 511-516
Opioids Accelerate Fetal Rat Lung Maturation In Vitro
Ira H.
Gewolb,
Janet
O'Brien,
and
Richard E.
Slavin
University of Maryland School of Medicine, Department of Pediatrics, Division of Neonatology, Baltimore, Maryland;
and Northeastern University College of Pharmacy and Allied Health, Department of Cardiopulmonary Sciences,
Boston, Massachusetts
Infants born to heroin- and cocaine-addicted mothers have been reported to have a lower incidence of respiratory distress syndrome (RDS) compared with nonaddicted infants. However, it is not known whether
these are direct drug-mediated effects or secondary phenomena. We therefore investigated the effect of
opioids and cocaine on fetal rat lung maturation in vitro. Using 18- to 20-d fetal rat lung explants and 20-d
fetal type II cells, we measured the effect of varying concentrations (1 × 10
8 to 1 × 103 M) of heroin,
morphine, methadone, and the nonopioid cocaine on the rate of choline incorporation into phosphatidylcholine (PC) and disaturated PC. We also analyzed the morphology of 19-d explants after exposure to opioids. Significant increases in rate of choline incorporation were noted in 19- and 20-d explants using 1 × 103 M heroin, 1 × 103 M morphine, and 1 × 104 M methadone (P < 0.005). No acceleratory effect
was seen with cocaine. Morphologic analysis of the three opioid-treated groups revealed a significant (192 to 251%) increase in type II pneumocytes and lamellar bodies per alveolar lining cell (P < 0.01). Choline incorporation into PC by type II cells was also significantly increased by opioids (P < 0.01); lactate dehydrogenase release and cell viability were not affected by opioid treatment. These data indicate that high-dose opioids have an acceleratory effect on biochemical and morphologic parameters of fetal lung maturation in vitro. The lack of in vitro acceleration with cocaine suggests that any cocaine-related reduction in
the incidence of RDS is a secondary effect.
