scholarly journals Hemodynamic and metabolic responses to moderate asphyxia in brain and skeletal muscle of late-gestation fetal sheep

2000 ◽  
Vol 88 (1) ◽  
pp. 82-90 ◽  
Author(s):  
J. P. Newman ◽  
D. M. Peebles ◽  
S. R. G. Harding ◽  
R. Springett ◽  
M. A. Hanson
Keyword(s):  
Redox State ◽  
Near Infrared ◽  
Metabolic Response ◽  
Hemoglobin Concentration ◽  
Late Gestation ◽  
Significant Drop ◽  
Fetal Sheep ◽  
Internal Iliac ◽  
Near Term ◽  
The Brain

The purpose of this study was to investigate metabolic and hemodynamic responses in two fetal tissues, hindlimb muscle and brain, to an episode of acute moderate asphyxia. Near-infrared spectroscopy was used to measure changes in total hemoglobin concentration ([tHb]) and the redox state of cytochrome oxidase (COX) simultaneously in the brain and hindlimb of near-term unanesthetized fetal sheep in utero. Oxygen delivery (Do 2) to, and consumption (V˙o 2) by, each tissue was derived from the arteriovenous difference in oxygen content and blood flow, measured by implanted flow probes. One hour of moderate asphyxia ( n = 11), caused by occlusion of the maternal common internal iliac artery, led to a significant fall in Do 2to both tissues and to a significant drop inV˙o 2 by the head. This was associated with an initial fall in redox state COX in the leg but an increase in the brain. [tHb], and therefore blood volume, fell in the leg and increased in the brain. These data suggest the presence of a fetal metabolic response to hypoxia, which, in the brain, occurs rapidly and could be neuroprotective.

scholarly journals Effects of thyroid hormones on pulmonary and renal angiotensin-converting enzyme concentrations in fetal sheep near term

2002 ◽  
Vol 173 (1) ◽  
pp. 143-150 ◽  
Author(s):  
AJ Forhead ◽  
AL Fowden
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Thyroid Hormones ◽  
Plasma Cortisol ◽  
Experimental Manipulation ◽  
Late Gestation ◽  
Converting Enzyme ◽  
Fetal Sheep ◽  
Near Term ◽  
Sheep Fetus

In the sheep fetus, pulmonary and renal concentrations of angiotensin-converting enzyme (ACE) increase towards term in parallel with the prepartum surges in plasma cortisol and tri-iodothyronine (T(3)). The ontogenic change in pulmonary ACE has been shown to be induced, at least in part, by cortisol but the role of the thyroid hormones is unknown. Therefore, this study investigated the effects of thyroid hormones on tissue ACE concentration in fetal sheep during late gestation. Pulmonary and renal ACE concentrations were measured in sheep fetuses after experimental manipulation of thyroid hormone status by fetal thyroidectomy and exogenous hormone infusion. In intact fetuses, pulmonary and renal ACE concentrations increased between 127-132 and 142-145 days of gestation (term 145 +/- 2 days), coincident with the prepartum rises in plasma cortisol and T(3). The ontogenic increment in pulmonary ACE concentration was abolished when the prepartum surge in T(3), but not cortisol, was prevented by fetal thyroidectomy. At 143-145 days, ACE concentration in the lungs and kidneys of the thyroidectomised fetuses were both lower than those in the intact fetuses. In intact fetuses at 127-132 days, pulmonary ACE was upregulated by intravenous infusions of either cortisol (2-3 mg/kg per day) or T(3) (8-12 microg/kg per day) for 5 days. Renal ACE was unaffected by cortisol or T(3) infusion. Therefore, thyroid hormones have an important role in the developmental control of pulmonary and renal ACE concentration in the sheep fetus towards term. In addition, the prepartum rise in plasma T(3) appears to mediate, in part, the maturational effect of cortisol on pulmonary ACE concentration.

scholarly journals Insulin Deficiency Alters the Metabolic and Endocrine Responses to Undernutrition in Fetal Sheep Near Term

Endocrinology ◽  
2012 ◽  
Vol 153 (8) ◽  
pp. 4008-4018 ◽  
Author(s):  
Abigail L. Fowden ◽  
Alison J. Forhead
Keyword(s):  
Oxygen Consumption ◽  
Metabolic Response ◽  
Plasma Concentrations ◽  
Late Gestation ◽  
Similar Degree ◽  
Hepatic Glycogen ◽  
Insulin Deficiency ◽  
Fetal Sheep ◽  
Maternal Undernutrition ◽  
Significant Fall

Insulin deficiency affects the adult metabolic response to undernutrition, but its effects on the fetal response to maternal undernutrition remain unknown. This study examined the effects of maternal fasting for 48 h in late gestation on the metabolism of fetal sheep made insulin deficient by pancreatectomy (PX). The endocrine and metabolic responses to maternal fasting differed between intact, sham-operated and PX fetuses, despite a similar degree of hypoglycemia. Compared with intact fetuses, there was no increase in the plasma concentrations of cortisol or norepinephrine in PX fetuses during maternal fasting. In contrast, there was a significant fasting-induced rise in plasma epinephrine concentrations in PX but not intact fetuses. Umbilical glucose uptake decreased to a similar extent in both groups of fasted animals but was associated with a significant fall in glucose carbon oxidation only in intact fetuses. Pancreatectomized but not intact fetuses lowered their oxygen consumption rate by 15–20% during maternal fasting in association with increased uteroplacental oxygen consumption. Distribution of uterine oxygen uptake between the uteroplacental and fetal tissues therefore differed with fasting only in PX fetuses. Both groups of fetuses produced glucose endogenously after maternal fasting for 48 h, which prevented any significant fall in the rate of fetal glucose utilization. In intact but not PX fetuses, fasting-induced glucogenesis was accompanied by a lower hepatic glycogen content. Chronic insulin deficiency in fetal sheep therefore leads to changes in the counterregulatory endocrine response to hypoglycemia and an altered metabolic strategy in dealing with nutrient restriction in utero.

scholarly journals Adrenal glands are essential for activation of glucogenesis during undernutrition in fetal sheep near term

2011 ◽  
Vol 300 (1) ◽  
pp. E94-E102 ◽  
Author(s):  
A. L. Fowden ◽  
A. J. Forhead
Keyword(s):  
Adrenal Glands ◽  
Metabolic Response ◽  
Glucose Production ◽  
Oxygen Metabolism ◽  
In Utero ◽  
Endogenous Glucose Production ◽  
Hepatic Glycogen ◽  
Fetal Sheep ◽  
Glucose Levels ◽  
Near Term

In adults, the adrenal glands are essential for the metabolic response to stress, but little is known about their role in fetal metabolism. This study examined the effects of adrenalectomizing fetal sheep on glucose and oxygen metabolism in utero in fed conditions and after maternal fasting for 48 h near term. Fetal adrenalectomy (AX) had little effect on the rates of glucose and oxygen metabolism by the fetus or uteroplacental tissues in fed conditions. Endogenous glucose production was negligible in both AX and intact, sham-operated fetuses in fed conditions. Maternal fasting reduced fetal glucose levels and umbilical glucose uptake in both groups of fetuses to a similar extent but activated glucose production only in the intact fetuses. The lack of fasting-induced glucogenesis in AX fetuses was accompanied by falls in fetal glucose ultilization and oxygen consumption not seen in intact controls. The circulating concentrations of cortisol and total catecholamines, and the hepatic glycogen content and activities of key gluconeogenic enzymes, were also less in AX than intact fetuses in fasted animals. Insulin concentrations were also lower in AX than intact fetuses in both nutritional states. Maternal glucose utilization and its distribution between the fetal, uteroplacental, and nonuterine maternal tissues were unaffected by fetal AX in both nutritional states. Ovine fetal adrenal glands, therefore, have little effect on basal rates of fetal glucose and oxygen metabolism but are essential for activating fetal glucogenesis in response to maternal fasting. They may also be involved in regulating insulin sensitivity in utero.

Distribution of calbindin-D28K in the brain of the fetal sheep in late gestation

1995 ◽  
Vol 675 (1-2) ◽  
pp. 303-315 ◽  
Author(s):  
T.J. McDonald ◽  
C. Li ◽  
R.H. Wasserman
Keyword(s):  
Late Gestation ◽  
Fetal Sheep ◽  
Calbindin D28k ◽  
The Brain

scholarly journals The resting-state fMRI arterial signal predicts differential blood transit time through the brain

2018 ◽  
Vol 39 (6) ◽  
pp. 1148-1160 ◽  
Author(s):  
Yunjie Tong ◽  
Jinxia (Fiona) Yao ◽  
J Jean Chen ◽  
Blaise deB Frederick
Keyword(s):  
Transit Time ◽  
Resting State ◽  
Time Delays ◽  
Carotid Arteries ◽  
Near Infrared ◽  
Low Frequency ◽  
Hemoglobin Concentration ◽  
Resting State Fmri ◽  
Single Subject ◽  
The Brain

Previous studies have found that aperiodic, systemic low-frequency oscillations (sLFOs) are present in blood-oxygen-level-dependent (BOLD) data. These signals are in the same low frequency band as the “resting state” signal; however, they are distinct signals which represent non-neuronal, physiological oscillations. The same sLFOs are found in the periphery (i.e. finger tips) as changes in oxy/deoxy-hemoglobin concentration using concurrent near-infrared spectroscopy. Together, this evidence points toward an extra-cerebral origin of these sLFOs. If this is the case, it is expected that these sLFO signals would be found in the carotid arteries with time delays that precede the signals found in the brain. To test this hypothesis, we employed the publicly available MyConnectome dataset (a two-year longitudinal study of a single subject) to extract the sLFOs in the internal carotid arteries (ICAs) with the help of the T1/T2-weighted images. Significant, but negative, correlations were found between the LFO BOLD signals from the ICAs and (1) the global signal (GS), (2) the superior sagittal sinus, and (3) the jugulars. We found the consistent time delays between the sLFO signals from ICAs, GS and veins which coincide with the blood transit time through the cerebral vascular tree.

scholarly journals The relationship of oxygen delivery to absolute haemoglobin oxygenation and mitochondrial cytochrome oxidase redox state in the adult brain: a near-infrared spectroscopy study

1998 ◽  
Vol 332 (3) ◽  
pp. 627-632 ◽  
Author(s):  
Chris E. COOPER ◽  
David T. DELPY ◽  
Edwin M. NEMOTO
Keyword(s):  
Infrared Spectroscopy ◽  
Cytochrome Oxidase ◽  
Near Infrared Spectroscopy ◽  
Oxygen Delivery ◽  
Redox State ◽  
Near Infrared ◽  
Adult Brain ◽  
Mitochondrial Cytochrome ◽  
The Brain ◽  
Mitochondrial Cytochrome Oxidase

Near-infrared spectroscopy was used to determine the effect of changes in the rate of oxygen delivery to the adult rat brain on the absolute concentrations of oxyhaemoglobin, deoxyhaemoglobin and the redox state of the CuA centre in mitochondrial cytochrome oxidase. The cytochrome oxidase detection algorithm was determined to be robust to large changes in haemoglobin oxygenation and concentration. By assuming complete haemoglobin deoxygenation and CuA reduction following mechanical ventilation on 100% N2O, the absolute concentration of oxyhaemoglobin (35 µM), deoxyhaemoglobin (27 µM) and the redox state of CuA (82% oxidized) were calculated in the normal adult brain. The mean arterial blood pressure was decreased by exsanguination. When the pressure reached 100 mmHg, haemoglobin oxygenation started to fall, but the total haemoglobin concentration and oxidized CuA levels only fell when cerebral blood volume autoregulation mechanisms failed at 50 mmHg. Haemoglobin oxygenation fell linearly with decreases in the rate of oxygen delivery to the brain, but the oxidized CuA concentration did not start to fall until this rate was 50% of normal. The results suggest that the brain maintains more than adequate oxygen delivery to mitochondria and that near-infrared spectroscopy may be a good measure of oxygen insufficiency in vivo.

scholarly journals GLUCOCORTICOID MATURATION OF MITOCHONDRIAL RESPIRATORY CAPACITY IN SKELETAL MUSCLE BEFORE BIRTH

2021 ◽  
Author(s):  
K L Davies ◽  
E J Camm ◽  
D.j. Smith ◽  
O.r. Vaughan ◽  
A J Forhead ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adenine Nucleotide ◽  
Uncoupling Protein ◽  
Supply And Demand ◽  
Biceps Femoris ◽  
Late Gestation ◽  
Mitochondrial Content ◽  
Fetal Sheep ◽  
Myosin Heavy Chain Isoform ◽  
Near Term

In adults, glucocorticoids act to match the supply and demand for energy during physiological challenges, partly through actions on tissue mitochondrial oxidative phosphorylation (OXPHOS) capacity. However, little is known about the role of the natural prepartum rise in fetal glucocorticoid concentrations in preparing tissues for the increased postnatal energy demands. This study examined the effect of manipulating cortisol concentrations in fetal sheep during late gestation on mitochondrial OXPHOS capacity of two skeletal muscles with different postnatal locomotive functions. Mitochondrial content, biogenesis markers, respiratory rates and expression of proteins and genes involved in the electron transfer system (ETS) and OXPHOS efficiency were measured in the biceps femoris (BF) and superficial digital flexor (SDF) of fetuses either infused with cortisol before the prepartum rise or adrenalectomised to prevent this increment. Cortisol infusion increased mitochondrial content, biogenesis markers, substrate-specific respiration rates and abundance of ETS Complex I and adenine nucleotide translocator (ANT1) in a muscle-specific manner that was more pronounced in the SDF than BF. Adrenalectomy reduced mitochondrial content and expression of PGC1α and ANT1 in both muscles, and ETS Complex IV abundance in the SDF near term. Uncoupling protein gene expression was unaffected by cortisol manipulations in both muscles. Gene expression of the myosin heavy chain isoform, MHCIIx, was increased by cortisol infusion and reduced by adrenalectomy in the BF alone. These findings show that cortisol has a muscle-specific role in prepartum maturation of mitochondrial OXPHOS capacity with important implications for the health of neonates born pre-term or after intrauterine glucocorticoid overexposure.

Impact of chronic hypoxemia on blood flow to the brain, heart, and adrenal gland in the late-gestation IUGR sheep fetus

2015 ◽  
Vol 308 (3) ◽  
pp. R151-R162 ◽  
Author(s):  
Rajan Poudel ◽  
I. Caroline McMillen ◽  
Stacey L. Dunn ◽  
Song Zhang ◽  
Janna L. Morrison
Keyword(s):  
Blood Flow ◽  
Cardiac Output ◽  
Adrenal Gland ◽  
Temporal Lobe ◽  
Late Gestation ◽  
Control Group ◽  
Surgical Removal ◽  
Fetal Sheep ◽  
Intrauterine Growth ◽  
The Brain

In the fetus, there is a redistribution of cardiac output in response to acute hypoxemia, to maintain perfusion of key organs, including the brain, heart, and adrenal glands. There may be a similar redistribution of cardiac output in the chronically hypoxemic, intrauterine growth-restricted fetus. Surgical removal of uterine caruncles in nonpregnant ewe results in the restriction of placental growth (PR) and intrauterine growth. Vascular catheters were implanted in seven control and six PR fetal sheep, and blood flow to organs was determined using microspheres. Placental and fetal weight was significantly reduced in the PR group. Despite an increase in the relative brain weight in the PR group, there was no difference in blood flow to the brain between the groups, although PR fetuses had higher blood flow to the temporal lobe. Adrenal blood flow was significantly higher in PR fetuses, and there was a direct relationship between mean gestational PaO2 and blood flow to the adrenal gland. There was no change in blood flow, but a decrease in oxygen and glucose delivery to the heart in the PR fetuses. In another group, there was a decrease in femoral artery blood flow in the PR compared with the Control group, and this may support blood flow changes to the adrenal and temporal lobe. In contrast to the response to acute hypoxemia, these data show that there is a redistribution of blood flow to the adrenals and temporal lobe, but not the heart or whole brain, in chronically hypoxemic PR fetuses in late gestation.

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