The response of the lamb ductus venosus to prostaglandins and inhibitors of prostaglandin and thromboxane synthesis.

Abstract

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)

Endothelin‐induced constriction of the ductus venosus in fetal sheep: developmental aspects and possible interaction with vasodilatory prostaglandin

“…A single animal at 98 days gestation (0.67 gestation) was also used for the morphological analysis (see below). At all ages, surgical procedure and procedure for isolating the ductus venosus followed a published protocol (Adeagbo et al, 1982). Rings of the ductus (width B3 mm), consisting of the inlet region (henceforth named sphincter preparation) or a section outside the sphincter (extrasphincter preparation), were then prepared taking care not to touch the luminal surface with sharp objects or damage the muscle in removing the adhering liver parenchyma.…”

“…As previously reported (Adeagbo et al, 1982;1985), ductal rings, intact (sphincter and extrasphincter) or endotheliumdenuded (sphincter), were suspended between platinum/ iridium hooks in a 20-ml organ bath, and their tension was recorded isometrically via a transducer (Grass FT 0.03C) coupled to a Grass polygraph. A smaller bath (capacity, 2.2 ml) was used when collecting fluid for the measurement of prostaglandins (see below).…”

“…The initial load on the preparation was adjusted gradually to 200-300 mg (100 mg weight ¼ 0.98 mN) with both preterm and term animals. This value had been extrapolated from the transmural tension in vivo (Adeagbo et al, 1982) and was kept constant regardless of age knowing that intraluminal pressure does not change appreciably during the last third of gestation (Nicolini et al, 1989;Weiner et al, 1989). Each bath was supplied from several reservoirs, and a system of three-way valves allowed the perfusion fluid to be changed rapidly.…”

“…According to some investigators, including us, this structure is a true sphincter with autonomous regulation of its muscle (see Coceani, 1993;Kiserud, 1999). We have shown, in particular, that the vessel wall is endowed with a noradrenergic innervation (Coceani et al, 1984) along with relaxing and contractile nonneural mechanisms that are, respectively, prostaglandin (conceivably PGI 2 )-and cytochrome P450 (CYP450)-linked (Adeagbo et al, 1982;1985;. In contrast to our position, however, Rudolph and his associates (Paulick et al, 1990;Rudolph et al, 1991) have argued that patency and closure are passive processes merely denoting an adjustment of the vessel wall to the prevailing hemodynamic state.…”

Intraobserver and interobserver variability of transabdominal Doppler velocimetry measurements of the fetal ductus venosus between 10 and 14 weeks of gestation

“…An alternative explanation is that the considerable variability seen in interobserver reproducibility could be due to physiological changes, which might have occurred in the DV. It has previously been described that the DV in fetal lambs is a reactive vessel, and its diameter may be controlled by a sphincter, which allows the DV to dilate or contract 13,14 . Although this is yet to be demonstrated in human fetuses, such a sphincter may alter the blood flow in DV considerably under different physiological conditions 15 and may account for the variability we observed.…”