Persistent patency of the ductus arteriosus (PDA) (a fetal vascular conduit that fails to close after birth) is a common cardiac problem in preterm infants.
In an analysis of findings from a previous clinical trial, Robert Cotton, M.D., Jeff Reese, M.D., and colleagues discovered an association between treatment of premature infants with the antacid cimetidine and PDA. Cimetidine inhibits histamine H2 receptors and also blocks certain cytochrome P450 enzymes (CYPs), which may play a role in DA closure.
Using mouse models, the researchers found that CYP enzymes are expressed in DA smooth muscle and that cimetidine and ranitidine (a related antacid) cause relaxation of term and preterm DA. They showed that the antacids relaxed the mouse DA by inhibiting CYP, not by blocking H2 receptors.
The findings, reported in the June Journal of Molecular and Cellular Cardiology, demonstrate an important role for CYP enzymes in perinatal vascular regulation and reveal that certain antacids and other CYP-inhibiting medicines pose a risk for PDA in critically ill newborns.
This research was supported by grants from the National Institutes of Health (HD044741, HL077395, HL096967, HL109199).
