SUMMARY Prostaglandin E2 (PGE2) has been used to maintain patency of the ductus arteriosus in four neonates with cyanotic congenital heart disease due to obstructive right heart malformations.PGE2 was infused prior to surgery, and in three patients, during surgery until a satisfactory aorto-pulmonary shunt was established. PGE2 produced consistently an immediate and persistent rise in arterial oxygen saturation, which could be ascribed to dilation of the CONGENITAL HEART DEFECTS which include pulmonary atresia, critical pulmonary stenosis or a severely hypoplastic right ventricle as part of the malformation are frequently almost entirely dependent on persistence of the ductus arteriosus for the maintenance of pulmonary blood flow. Likewise, interruption of the aortic arch requires ductus patency for blood flow to the lower half of the body. Patients in either group usually become extremely sick in the first few days of life as the ductus constricts and without intervention they generally die within the first month. Even when referred to an investigative center, they are frequently so ill by the time investigation is undertaken that subsequent palliative surgery carries a high mortality.The original demonstration by Coceani and Olley that Etype PGs are potent relaxants of the ductus arteriosus,' confirmed by subsequent animal studies by others in vitro2 and in vivo,3 suggested their use in these patients. Administration of PG to reverse ductus constriction and increase pulmonary blood flow should improve tissue oxygenation, permit correction of metabolic acidosis, and improve the chances of successful surgery. Similar reasoning was followed by Elliott et al.4 when they infused PGE1 in two infants with cyanotic heart disease in whom surgery was refused by the parents.In this paper we describe the use of PGE, as a preparation for surgery in three patients and postoperatively in one patient in whom surgery was unsuccessful. Part of this work has been reported briefly.5Materials and Methods PGE2 (Prostin E2, Upjohn Co.) has been used in all patients. Its effectiveness was first evaluated during diagnostic cardiac catheterization. Once the diagnostic procedure was completed, an infusing catheter introduced into the femoral vein was placed as close to the aortic end of the ductus as possible, either being in the left ventricle via the foramen ovale or in the aortic root through a ventricular

Circular strips of ductus arteriosus from lambs of gestational age between 90 and 144 days (term 147 days) were studied in vitro at low (8--16 torr (1 torr = 133.322 Pa)) and high (426--622 torr) PO2. Potassium- and oxygen-induced contractions increased with the gestational age and attained a maximum at term. At low PO2, ibuprofen, a blocker of prostaglandin synthesis, produced a dose-dependent contraction of the ductus at all ages and enhanced the potassium-induced contraction of the immature ductus (90--124 days). Both effects were relatively greater in the 103- to 107-day gestational group. At that age, ibuprofen also potentiated the oxygen-induced contraction. These findings, while confirming that a prostaglandin is involved in ductus patency, indicate that the prostaglandin-relaxing mechanism becomes functional at an early stage of gestation and reaches maximal activity before term. The existence of an active, prostaglandin-mediated relaxation in the preterm ductus may account, in part, for the reduced responsiveness of the vessel to oxygen. It is confirmed that ibuprofen and other nonsteroidal antiinflammatory drugs are well suited for the management of the premature infant with patent ductus arteriosus.

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Prostaglandin (PG) E2, the PG endoperoxides PGG2 and PGH2, and enzymatically generated PGI2 and thromboxane A2 (TXA2) were tested in vitro on circular strips of ductus arteriosus from mature fetal lambs. Both PGE2 and the PG endoperoxides produced a dose-dependent relaxation of the ductus at low PO2 (7-11 torr), and their action was reduced or abolished at high PO2 (410-660 torr). PGE2, however, was more potent than the endoperoxides. The reaction mixture containing PGI2 relaxed the hypoxic ductus, but this response was not due to PGI2 but to two, more stable and as yet unidentified, compounds, one of which is most certainly PGE2. TXA2 was inactive on the vessel at low and high PO2. These results confirm that PGE2 is the most effective PG acting on the ductus and provide further support to the hypothesis that this PG is responsible for patency of the vessel during fetal life. PGE2 action, however, may be complemented by that of another endoperoxide derivative formed in the PGI2 synthetic reaction which remains to be identified.