Time Course of Closure of the Ductus Venosus in the Newborn Lamb

Zink, J; Petten, G. R. Van

doi:10.1203/00006450-198014010-00001

Cited by 10 publications

(14 citation statements)

References 4 publications

(8 reference statements)

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“…Excretion of pnitrophenol conjugates into the bile was, however, low in both foetal and neonatal livers, and we cannot speculate on the maturity of this process given that the capacity of biliary excretion of p-nitrophenol conjugates in the adult sheep liver is unknown. In all of these experiments, use of the radiolabeled microsphere technique allowed hepatic drug extraction in the neonate to be readily corrected for ductus venosus shunt which gradually closed over the first 10 days of life, consistent with previous reports (Zink & Van Petten 1980). This work shows that the capacities of oxidative and conjugative drug clearance increase substantially in the intact liver shortly after birth.…”

Section: Drug Elimination By the Perfused Neonatal Liversupporting

confidence: 88%

“…In the lamb, the patency of the ductus venosus clearly persists during the first week of life and is highly variable (Zink & Van Petten 1980), but minimal by day seven. Human studies, performed using doppler ultrasound, have not been able to directly quantitate the magnitude of the ductus venosus shunt.…”

Section: Neonatal Liver Blood Flowmentioning

confidence: 99%

“…Using microsphere studies in sheep, the magnitude of the ductus venosus shunt gradually decreases from foetal (53%), newborn (23%) one week old (9%) through to adult (0%) life (Zink & Van Petten 1980;Edelstone et al 1978). In the lamb, the patency of the ductus venosus clearly persists during the first week of life and is highly variable (Zink & Van Petten 1980), but minimal by day seven.…”

Section: Neonatal Liver Blood Flowmentioning

confidence: 99%

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Neonatal Hepatic Drug Elimination

Gow

Ghabrial

Smallwood

et al. 2001

Pharmacology & Toxicology

104

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After the transition from in utero to newborn life, the neonate becomes solely reliant upon its own drug clearance processes to metabolise xenobiotics. Whilst most studies of neonatal hepatic drug elimination have focussed upon in vitro expression and activities of drug-metabolising enzymes, the rapid physiological changes in the early neonatal period of life also need to be considered. There are dramatic changes in neonatal liver blood flow and hepatic oxygenation due to the loss of the umbilical blood supply, the increasing portal vein blood flow, and the gradual closure of the ductus venosus shunt during the first week of life. These changes which may well affect the capacity of neonatal hepatic drug metabolism. The hepatic expression of cytochromes P450 1A2, 2C, 2D6, 2E1 and 3A4 develop at different rates in the postnatal period, whilst 3A7 expression diminishes. Hepatic glucuronidation in the human neonate is relatively immature at birth, which contrasts with the considerably more mature neonatal hepatic sulfation activity. Limited in vivo studies show that the human neonate can significantly metabolise xenobiotics but clearance is considerably less compared with the older infant and adult. The neonatal population included in pharmacological studies is highly heterogeneous with respect to age, body weight, ductus venosus closure and disease processes, making it difficult to interpret data arising from human neonatal studies. Studies in the perfused foetal and neonatal sheep liver have demonstrated how the oxidative and conjugative hepatic elimination of drugs by the intact organ is significantly increased during the first week of life, highlighting that future studies will need to consider the profound physiological changes that may influence neonatal hepatic drug elimination shortly after birth.The development of clinical pharmacology has resulted in a more rational approach to drug therapy, as well as a deeper understanding of the factors capable of influencing drug disposition, and hence drug effects. Of these factors, age is of great importance. However, substantial differences in drug disposition not only exist between neonates and adults, but also among premature neonates, term neonates, infants and children.During the last two decades drug disposition in the neonatal period has been studied extensively. A major impetus for these studies seems to have been a series of incidents involving illness or death following the administration of drugs at ratios of dose/body weight innocuous in an adult (Craft et al. 1974;Gershanik et al. 1982). These studies have shown that the transition from neonate to childhood is characterised by the ontogeny of all of the processes of drug absorption, distribution, hepatic metabolism and renal excretion, with the development of hepatic drug metabolism being particularly important.The extent to which the neonatal drug-metabolising en-

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Section: Drug Elimination By the Perfused Neonatal Liversupporting

confidence: 88%

Section: Neonatal Liver Blood Flowmentioning

confidence: 99%

Section: Neonatal Liver Blood Flowmentioning

confidence: 99%

See 1 more Smart Citation

Neonatal Hepatic Drug Elimination

Gow

Ghabrial

Smallwood

et al. 2001

Pharmacology & Toxicology

104

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“…After birth, the ductus ceases its function and undergoes closure, but the timing of this process varies individually and between species so that the vessel may persist for a certain period as a portocaval shunt (Zink & Van Petten, 1980;Momma et al, 1992;Fugelseth et al, 1997). The issue of whether prenatal patency and postnatal closure are actively or passively determined has been debated through the years, the specific point of contention being the functional significance of a tissue ridge at the junction of the ductus with the portal sinus (Coceani, 1993;Kiserud, 1999;Mavrides et al, 2002;Ailamazyan et al, 2003;Tchirikov et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

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

Adeagbo

Kelsey

Coceani

2004

British J Pharmacology

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1 The ductus venosus is actively regulated in the fetus, but questions remain on the presence of a functional sphincter at its inlet. Using fetal sheep (0.6-0.7 gestation onwards), we have examined the morphology of the vessel and have also determined whether endothelin-1 (ET-1) qualifies as a natural constrictor being modulated by prostaglandins (PGs). 2 Masson's staining and a-actin immunohistochemistry showed a muscular, sphincter-like formation at the ductus inlet and a muscle layer within the wall of the vessel proper. This muscle cell component increased with age. 3 ET-1 contracted dose-dependently isolated sphincter and extrasphincter preparations of the ductus from term fetus. This ET-1 effect also occurred in the premature, but its threshold was higher. 4 BQ123 (1 mM) caused a rightward shift in the ET-1 dose-response curve, while indomethacin at a threshold concentration (28 nM) tended to have an opposite effect. 5 Big ET-1 also contracted the ductus sphincter but differed from ET-1 for its lesser potency and inhibition by phosphoramidon (50 mM). 6 The ductus sphincter (term and preterm) and extrasphincter (term) released 6-keto-PGF 1a (hence PGI 2 ) and, to a lesser degree, PGE 2 at rest and their release increased dose-dependently upon ET-1 treatment. Both basal and stimulated release was curtailed by endothelium removal. 7 BQ123 and phosphoramidon reduced slightly the contraction of ductus sphincter to indomethacin (2.8 mM). 8 We conclude that the ductus contains a contractile mechanism in the sphincter and extrasphincter regions. ET-1 lends itself to a role in the generation of contractile tone and its action may be modulated by prostaglandins.

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“…In the immediate postnatal period, some portal venous blood is shunted through the persistent DV. This large, highly variable, postnatal DV shunt may represent up to 40% of total portal venous return in the 1-d-old lamb (5,6). The effect of the DV shunt on total hepatic blood flow in the first hours after birth is not known, and the exact time course of the transition from higher fetal to lower postnatal hepatic blood flow has not been sequentially measured.…”

mentioning

confidence: 99%