Opioids accelerate fetal rat lung maturation in vitro.
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 x 10(-8) to 1 x 10(-3) 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 x 10(-3) M heroin, 1 x 10(-3) M morphine, and 1 x 10(-4) 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.
Gewolb
I H
IH
University of Maryland School of Medicine, Department of Pediatrics, Division of Neonatology, Baltimore, Maryland 21201, USA. igewolb@peds05.ab.umd.edu
O'Brien
J
J
Slavin
R E
RE
D000818:Animals; D003042:Cocaine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D003932:Heroin / Q000494:pharmacology*; D066298:In Vitro Techniques; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000196:embryology*; D008691:Methadone / Q000494:pharmacology*; D009020:Morphine / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D009294:Narcotics; D003932:Heroin; D009020:Morphine; D003042:Cocaine; D008691:Methadone