Therapeutic manipulation of the ductus arteriosus: current options and future prospects

The ductus arteriosus is a large fetal vessel connecting the pulmonary artery with the aorta and allowing right ventricular blood to bypass the unexpanded lungs. At birth, with the start of lung ventilation and the attendant rise in blood oxygen tension, the ductus closes and the cardiovascular system acquires its final arrangement. However, in the prematurely born infant, this shunt may remain patent (patent ductus arteriosus--PDA) with adverse consequences on hemodynamic homeostasis. Conversely, there are cardiac malformations in which patency of the duct is required to maintain the pulmonary or systemic circulation prior to corrective surgery. Based on the notion that patency is an active process sustained primarily by prostaglandin (PG) E₂, PDA is currently managed with synthesis inhibitors, indomethacin or ibuprofen, while any necessary persistence of the duct after birth is achieved with the infusion of PGE₁. However, the former procedure presents a relatively high incidence of failures for the likely combination of the 2 events: the relaxing influence of the agents compensating for the loss of PGE₂ and the immaturity of the oxygen‑triggered contractile mechanism. On the other hand, PGE₁ treatment loses some of its efficacy with time and may also be complicated by troublesome side effects. This article presents possible new approaches to therapy still based on the manipulation of the relaxing mechanism(s) responsible for duct patency. At the same time, however, the idea is put forward that the management of these sick infants may find its definitive solution only with tools being designed on the operation of the oxygen‑sensing/effector system.