Blood flow to and the metabolism of glucose and lactate by the liver in vivo in fetal, newborn and adult sheep.

Apatu, R. S. K.; Barnes, Richard

doi:10.1113/jphysiol.1991.sp018559

Cited by 18 publications

(23 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Reports of hepatic oxygen consumption both in the foetal lamb and neonate vary in the literature. The general consensus is that consumption (mmol/min./g liver) is around 1.1-1.8 in the near-term foetus (Bristow et al 1983;Apatu et al 1991), 1.3-2.2 in newborns (Townsend et al 1989;Apatu et al 1991), rising to 3.2 in the 1 week old neonate (Gleason et al 1985;Townsend et al 1989), and falling to 1.3-1.6 in young lambs and adults (Apatu et al 1991). The figure of 3.2 mmol/min./g liver in the 1 week old neonatal lamb is approximately twice that seen in adult animals of a number of species (Harrison et al 1972;Lautt 1977;Hughes et al 1981).…”

Section: Neonatal Hepatic Oxygenationmentioning

confidence: 99%

Neonatal Hepatic Drug Elimination

Gow

Ghabrial

Smallwood

et al. 2001

Pharmacology & Toxicology

104

View full text Add to dashboard Cite

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-

show abstract

Section: Neonatal Hepatic Oxygenationmentioning

confidence: 99%

Neonatal Hepatic Drug Elimination

Gow

Ghabrial

Smallwood

et al. 2001

Pharmacology & Toxicology

104

View full text Add to dashboard Cite

show abstract

“…Full details of the methods for insertion of intra-vascular catheters and Caesarean delivery have already been published (Apatu & Barnes, 1991).…”

Section: Surgical Procedures and Anaesthesiamentioning

confidence: 99%

“…The housing, feeding and pre-operative treatment have been described elsewhere (Comline & Silver, 1972; Apatu, 1985;Apatu & Barnes. 1991).…”

Section: Animalsmentioning

confidence: 99%

“…In each group in each animal the study consisted of up to six measurements of blood flow and metabolism using radioactive microspheres and the Fick principle (Apatu & Barnes, 1991). Measurements of blood flow and metabolism were made serially (a) before any infusion, (b) after infusion of either adrenaline or noradrenaline for 10 min.…”

Section: Experimental Protocolsmentioning

confidence: 99%

“…It has been suggested that circulating catecholamines might stimulate glucose release from the liver at birth (Dawes & Shelley, 1968;Jones & Ritchie, 1978;Apatu & Barnes, 1991).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Release of glucose from the liver of fetal and postnatal sheep by portal vein infusion of catecholamines or glucagon.

Apatu

Barnes

1991

The Journal of Physiology

Self Cite

View full text Add to dashboard Cite

SUMMARY1. The blood flow to the liver in fetuses near term, newborn and adult sheep was measured by the Fick principle, using radionuclide-labelled plastic microspheres, before and during infusion of adrenaline, noradrenaline or glucagon.2. Glucose output and lactate consumption by the liver in sheep of each age group were calculated by application of the Fick principle using the concentration gradients of these metabolites measured in blood samples obtained, simultaneously with blood flow measurements, from catheters chronically implanted in the inflow and outflow vessels of the liver.3. Catecholamines were infused into the portal vein of fetuses near term at a rate comparable with that at which they are known to be secreted in the sheep fetus during moderate to severe hypoxia. The cardiovascular and metabolic responses to these infusions were found to be comparable with those that occur in the fetus during hypoxia.4. Catecholamines increased glucose output from the liver in all except the immediate post-partum animals. Catecholamines were less effective than glucagon in promoting glucose release. The mean increments in glucose output during adrenaline infusion were 0055+0-015 mmol min-(100 g liver)-1 in the fetus, 0-122+ 0024 mmol min-(100 g)-1 in the 2-week-old lambs, 0078+0019 mmol min-' (100 g)-' in young lambs and 0-049+0-012 mmol min-' (100 g)-' in the adult sheep.During glucagon infusion the mean glucose output increments were 0-146 + 0023 mmol min-1 (100 g)-in the fetus, 0-274+0-085 mmol min-(100 g)-1 in the 2-week-old and young lambs and 0 180+0-054 mmol min-' (100 g)-1 in the adult. Adrenaline was more potent than noradrenaline, suggesting that the major glycogenolytic response might be f-receptor mediated.5. In the immediate newborn period the output of glucose from the liver was high (0-20 + 0-05 mmol min-' (100 g liver)-' and was not statistically significantly increased by infusion either of glucagon or of catecholamines which resulted in similar increments of glucose output of about 04128 +0-133 mmol min-' (100 g)-1. It is probable that the high output of glucose reflected the high endogenous circulating levels of catecholamines and glucagon in these animals at birth and that further infusions failed to add significantly to the already near-maximal glucose release. R. S. K. APATU AND R. J. BARNES absence of high levels of circulating catecholamines and glucagon in the resting fetus but also may indicate a deficiency in either the receptor mechanism for catecholamines or of the intracellular second messenger system for glycogenolysis. The greater effectiveness of glucagon (than adrenaline) as a mediator of glucose release in these animals tends to support the idea of a fl-receptor rather than a second messenger deficiency. It is postulated that a deficiency of hepatic ,-adrenergic receptors, provided that it can be corrected in time for birth, would help to protect glycogen stores in the liver in utero.

show abstract

Oxygen Consumption and General Carbohydrate Metabolism of the Fetus

Philipps¹

2017

Fetal and Neonatal Physiology

View full text Add to dashboard Cite

Blood flow to and the metabolism of glucose and lactate by the liver in vivo in fetal, newborn and adult sheep.

Cited by 18 publications

References 37 publications

Neonatal Hepatic Drug Elimination

Neonatal Hepatic Drug Elimination

Release of glucose from the liver of fetal and postnatal sheep by portal vein infusion of catecholamines or glucagon.

Oxygen Consumption and General Carbohydrate Metabolism of the Fetus

Contact Info

Product

Resources

About