The control of cardiovascular shunts in the fetal and perinatal period

Abstract

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.

Changing Expression of Cyclooxygenases and Prostaglandin Receptor EP4 During Development of the Human Ductus Arteriosus

“…It is known that this complex alteration process already starts during gestation and involves several pathways, among which the PG metabolism seems to play a major role (12,13). Until now, expression of the key factors of the PG metabolism, both COX isoforms and the EP4 receptor, has only been examined in fetal DA tissue from various animal species.…”

Identification of a New Class of Prostaglandin Transporter Inhibitors and Characterization of Their Biological Effects on Prostaglandin E2 Transport

“…PGs play an important role in physiology and clinical settings. Their biological effects include triggering inflammation, fever, and pain (Blatteis and Sehic, 1997;Bley et al, 1998;Vanegas and Schaible, 2001;Samad et al, 2002); induction of labor (Ulmann et al, 1992); modulation of renal hemodynamics and of water and solute reabsorption (Epstein, 1986;Wang et al, 1998;Yokoyama et al, 2002); and arterial vasodilatation (Clyman et al, 1978;Coceani and Olley, 1988;Smith et al, 1994). PG analogs, such as latanoprost and unoprostone, have been used to treat glaucoma (Stjernschantz, 1995(Stjernschantz, , 2004Alm, 1998;Susanna et al, 2002).…”

Gene Transfer of Prostaglandin Synthase Maintains Patency of the Newborn Lamb Arterial Duct

“…Among different mammalian species there are changes in expression of these enzymes in the preand postnatal periods (17,29). The HVJ-liposomes penetrate the media and intima of the DA, where circulating PGE 2 is produced (5,30,31).…”

“…Following the instructions of the manufacturer, cells were harvested and centrifuged at 300 ϫ g for 5 min, then disrupted using a buffer with ␤-mercaptoethanol. Homogenization was achieved by passing the lysate five times through a 20-G needle fitted to a syringe; 70% ethanol was added and the mixture was centrifuged at 8500 ϫ g. After washing and elution, the RNA was collected in RNase-free water, followed by reverse transcription with SuperScriptII reverse transcriptase and 0.5 g Oligo(dT) (3,5,(13)(14)(15)(16)(17) primer in accordance with the manufacturer's instructions (Invitrogen, Burlington, ON, Canada). PGE-synthase cDNA was amplified using a forward 22SC (5'-TGCCCACAGCCTGGTGATGA-3') and a reverse 23SC primer (5'-AGCTGGCAGACACTTCCATTTA-3').…”

“…Gene transfer of PGE synthase to the DA is feasible and will maintain patency for at least In congenital heart disease with left-or right-sided obstruction, PGE 1 (alprostadil) or PGE 2 (dinoprostone) is infused to maintain patency of the DA. Although the DA produces endogenous PGE 2 (1), the dilatory capacity of this compound decreases with time due to the accelerated production of the vasoconstrictor ET-1 (2) in response to oxygen (3) and the reduced expression of PGE 2 receptor(s) (4,5). However, prolonged PGE infusion is problematic as a result of tachyphylaxis and major side effects, including respiratory depression, which may require mechanical ventilation, systemic hypotension, bradycardia, irritability, fever, lethargy, gastric-outlet obstruction, and hyperostosis (6 -10).…”