Fetal reversed constrictive effect of indomethacin and postnatal delayed closure of the ductus arteriosus following administration of transplacental magnesium sulfate in rats.
BACKGROUND
Magnesium sulfate (MgSO4) is used therapeutically for eclampsia and tocolysis. Some reports have suggested a relationship between therapeutic MgSO4 and patent ductus arteriosus (DA) in preterm infants.


OBJECTIVE
To clarify patent DA induction by MgSO4 in preterm infants, we studied the increase in serum Mg concentrations and fetal dilatation and postnatal delayed closure of the ductus, using transplacental MgSO4 in rats.


METHODS
Fetal and neonatal ductus diameters were measured with a microscope and a micrometer after rapid whole-body freezing. In the postnatal study, 21-day pregnant dams were administered a subcutaneous injection of MgSO4 1-3 h before delivery, and the ductus was studied 0, 15, 30, 60 and 120 min after birth. In the fetal study, MgSO4 (1 g/kg) and indomethacin (10 mg/kg) were simultaneously administered to 21-day dams and the fetal ductus was studied 1, 2 and 4 h later. Serum Mg concentration was measured in the dams and newborns.


RESULTS
Neonatal Mg concentrations increased from 3.8 to 4.7 and 5.8 mg/dl at 1 and 3 h after maternal administration of MgSO4. Following MgSO4 administration 3 h before birth, closure of the neonatal DA was delayed. The ductus diameter was 0.88 mm (0.80 mm in control) at 0 min, and 0.26 mm (0.08 mm in the control) at 60 min after birth. In the fetal study, MgSO4 initially reversed and later attenuated the ductus-constricting effect of indomethacin.


CONCLUSIONS
Hypermagnesemia induced by transplacental MgSO4 attenuates the fetal ductus-constricting effects of indomethacin, and delays postnatal ductal closure in rats.
Toyoshima
Katsuaki
K
Section of Pediatric Cardiology, Tokyo Women's Medical University, Tokyo, Japan. nqf37179@nifty.com
Momma
Kazuo
K
Nakanishi
Toshio
T
D000818:Animals; D000831:Animals, Newborn; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D004195:Disease Models, Animal; D004336:Drug Antagonism; D004373:Ductus Arteriosus / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D004374:Ductus Arteriosus, Patent / Q000188:drug therapy* / Q000473:pathology; D004622:Embryo, Mammalian / Q000187:drug effects / Q000196:embryology; D005260:Female; D007213:Indomethacin / Q000494:pharmacology*; D008278:Magnesium Sulfate / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D008431:Maternal-Fetal Exchange; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D015149:Tocolytic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015149:Tocolytic Agents; D008278:Magnesium Sulfate; D007213:Indomethacin