The fetal circulation has two major vascular shunts, the ductus arteriosus and the ductus venosus. The ductus arteriosus connects the pulmonary artery with the descending portion of the aortic arch, hence shunting most of the right ventricular output away from the unexpanded lungs. The ductus venosus connects instead the portal sinus with the inferior vena cava and allows well-oxygenated umbilical vein blood to bypass the liver and reach the central circulation rapidly. Both blood vessels cease their function after birth and undergo permanent closure. It is now well established that prenatal patency of the ductus arteriosus is an active state sustained by a prostaglandin. A similar mechanism has been recently recognized in the fetal ductus venosus. Evidence is presented indicating that prostaglandin E2 and prostaglandin I2 are natural relaxants, respectively, for the ductus arteriosus and the ductus venosus. In addition, both vascular shunts share the dependence on an endogenous cytochrome P-450 mechanism to develop their contractile tone. This mechanism may be important in the normal process of shunt closure at birth. While broadening the knowledge of fetal cardiovascular homeostasis, advances in this field have important implications for the prevention and management of certain pathological conditions affecting the newborn.
Morphological and pharmacological studies were performed in the ductus venosus from near-term fetal and neonatal (1 day of age) lambs. Light and electron microscopic analysis demonstrated a concentration of circularly oriented muscle fibers at the junction of the ductus with the portal sinus (the sphincter region). With the use of histochemical methods, adrenergic and cholinergic fibers were visualized in both the sphincter and extrasphincter regions of the ductus. At either site, nerve fibers were confined to the adventitial layer and never formed a plexus. Norepinephrine and transmural electrical stimulation contracted the ductus sphincter in vitro, and their action was abolished by dibenzyline. In contrast, atropine had no effect on the transmural response. Moreover, acetylcholine contracted the vessel inconsistently. In the fetus, both the norepinephrine-induced and the electrically induced contractions increased on raising the O2 tension of the bathing fluid from 17-31 to 520-705 mmHg. In addition, the transmural response increased with advancing gestation. Norepinephrine and transmural stimulation relaxed dibenzyline-treated preparations in which the tone had been raised with indomethacin. Norepinephrine relaxation was antagonized by propranolol. We conclude that the ductus venosus sphincter contains functional adrenergic nerves, causing contraction and relaxation via, respectively, alpha- and beta-adrenoceptors. The alpha-adrenoceptor-mediated contraction may have a role in postnatal closure of the vessel.
During the past 4 years, five institutions have collaborated in evaluating the efficacy of blade atrial septostomy. The procedure was performed in 52 patients, including 31 with transposition of the great arteries, 10 with mitral atresia, five with tricuspid atresia and six with miscellaneous anomalies. The patient's ages ranged from 1 day to 12 years (mean 13 months). Improvement occurred in 41 of 52 patients (79%). Four patients had an intact interatrial septum, and blade atrial septostomy was successfully performed by a transseptal technique. One patient died from a lacerated left atrial wall; other complications occurred in four patients. Blade atrial septostomy is an effective palliative procedure, even when the interatrial septum is thickened or intact.
SUMMARY. Rings of the umbilical end of the ductus venosus (the so-called sphincter) from nearterm fetal and newborn (1-3 days of age) lambs were studied in vitro at low (17-31 mm Hg) and high (504-705 mm Hg) P02. Tissues developed a modest contraction upon exposure to a high P02; however, this contraction generally was not sustained and tended to be greater in the fetus than in the newborn. In contrast, excess potassium (55 min) produced a sustained contraction whose magnitude was greater in the newborn. The cyclooxygenase inhibitor, indomethacin, contracted both the fetal and the neonatal ductus venosus; however, responses in the newborn were often not maintained. Furthermore, indomethacin enhanced the potassium response in the fetus, whereas it had no significant effect in the newborn. The thromboxane synthesis inhibitor, compound OKY-1581, was ineffective in either age group. Prostaglandin (PG) E2 and PGI 2 relaxed the ductus venosus, the former being slightly more potent. Conversely,stable PG endoperoxide analogs (9a,lla-epoxymethano and 9a,lla-methano-epoxy compounds) and PGF20 were contractile agents. Endoperoxide analogs were more effective in the newborn than the fetus and their action consistently exceeded that of PGF20. We conclude that the ductus venosus sphincter is endowed with functional muscle cells. These cells are under the influence of a relaxing product of the cyclooxygenase reaction which may be identified with either PGE2 or PGI2. This prostaglandin-mediated relaxing mechanism may contribute to prenatal patency of the vessel. Postnatal closure of the ductus venosus is unlikely to be a direct effect of oxygen on the sphincter muscle. The prostaglandin endoperoxides, however, are well suited for playing a role in the latter process. (Circ Res 51: 580-586, 1982)
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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