New Insights on How to Treat Patent Ductus Arteriosus

Abstract

The ductus arteriosus (DA) must be closed after birth for the establishment of adult circulation. Extremely preterm infants, however, frequently have patent ductus arteriosus (PDA), which associates with significant morbidity and mortality. At birth, the separation of the fetus from its maternal environment constitutes a dramatic change for the infant. Initiation of respiration changes serum composition and oxygen tension resulting in the closure of the DA. We found that serum osmolality was significantly decreased early after birth in rats, and that the hypo-osmolality sensor transient receptor potential melastatin (TRPM) 3 had increased expression in the rat DA compared to the aorta. Our data suggest that a decrease in serum osmolality promotes DA closure via TRPM3 and that an increase in osmolality dilates the DA. For extremely preterm infants, recent recommendations include immediate amino acid supplementation. We examined plasma amino acid composition and found an association between low glutamate concentration and PDA. Our data suggest that glutamate induces DA contraction through the AMPA receptor GluR-mediated noradrenaline production. Based on these data, maintaining proper levels of serum osmolality and amino acid composition may improve the therapeutic outcome of PDA in extremely preterm infants.