Biomedical subjects

G Meschia

Publications and source records attributed to G Meschia.

At least 55 records · Page 3Linked to original sources

PubMed1990

Fetoplacental deamination and decarboxylation of leucine.

Fetal and placental metabolism of leucine (Leu) and ketoisocaproic acid (KIC) were studied in seven fetal lambs at 132 +/- 1.3-days gestation. Fetal infusions of [1-13C]Leu, [1-14C]Leu, and antipyrine were carried out for 4 h. Uterine and umbilical blood flows were measured using the antipyrine steady-state diffusion technique. Leu and KIC concentrations, [14C]Leu-specific activities, 14CO2, [13C]Leu, and [13C]KIC enrichment (mole percent enrichment) were measured in the maternal artery, uterine vein, and umbilical artery and vein to calculate net fluxes of tracee and tracer molecules between fetus and placenta and between the uteroplacenta and the maternal circulation. There were net Leu and KIC fluxes into the fetus from the placenta with the KIC flux equal to approximately 19% of the combined Leu plus KIC flux. In addition, there was a net KIC flux into the uterine circulation. The fraction of infused tracer Leu escaping the placenta into the mother was small (approximately 6%). By contrast, there was a rapid exchange of tracer Leu carbon between placenta and fetus resulting in a significant flux of labeled KIC from placenta to fetus. Approximately 20% of the infused tracer carbon was converted to CO2 within the fetus. This rate of conversion was greater than 80% of the total fetoplacental conversion rate and significantly higher than the flux of KIC tracer carbon from placenta to fetus. Fetal KIC decarboxylation rate, calculated from the fetal KIC enrichment data, was 2.83 +/- 0.40 mumol.min-1.kg fetus-1 and approximately 60% of the combined net Leu and KIC flux into the fetus from the placenta.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Model of placental glucose consumption and glucose transfer.

Net ovine uteroplacental glucose consumption (Ro,up) and transfer rates to the fetus (Rf,up) were measured at different concentrations of maternal (GA) and fetal (Ga) arterial plasma glucose that were set and maintained independently by a glucose clamp procedure. Five GA/Ga combinations were studied: 70/15, 70/20, 70/30, 50/14, and 50/24 mg/dl. Rf,up was inversely related to Ga both at GA = 70 and GA = 50. Linear regression analysis of Rf,up vs. Ga for the GA = 70 and GA = 50 groups of observations revealed similar slopes (-0.286 +/- 0.012 vs. -0.217 +/- 0.028 dl.min-1.kg fetus-1) but a significantly higher intercept for the GA = 70 group (10.3 +/- 0.12 vs. 5.5 +/- 0.47 mg.min-1.kg fetus-1). In contrast, Ro,up increased significantly in response to an increase of Ga and had no significant dependence on GA. These results indicate that uteroplacental glucose metabolism occurs primarily in tissues that have direct access to glucose molecules carried by the umbilical circulation and that the glucose transport capacity of the placental barrier is greater on its fetal than its maternal surface. Uteroplacental glucose metabolic rate and its dependence on fetal glucose concentration are major factors that determine the magnitude and variability of the glucose concentration gradient (and thus the rate of net glucose transfer) between maternal and fetal plasma.

Animals↗

PubMed1990

Fetal hind limb oxygen consumption and blood flow during acute graded hypoxia.

Hind limb blood flow and O2 uptake, mean blood pressure, and heart rate were measured in six fetal sheep at 127-141 d gestation in the control state and at different levels of hypoxia that were induced by partial occlusion of the maternal terminal aorta. Blood flow was measured by an ultrasonic flow transducer. Control fetal arterial O2 content ([O2]a) in the descending aorta was 3.25 + 0.17 mM. In response to graded acute hypoxia, blood flow first increased (22.2 versus 19.9 mL.min-1.100 g-1, p = 0.003) and then decreased abruptly at approximately 1.5 mM [O2]a.O2 uptake decreased about 12% (14.74 versus 16.71, p = 0.03) as [O2]a decreased to 1.5 mM, and then fell markedly, tending toward zero for [O2]a = 0.9 mM. In the 2.7- to 1.5-mM [O2]a range, heart rate increased above control (194 versus 169 min-1, p = 0.0024), whereas mean blood pressure did not change significantly. For [O2]a less than 1.5 mM, heart rate decreased to 148 min-1 (p = 0.0005) and mean blood pressure increased above baseline (55 versus 47 torr, p = 0.0001). In conjunction with previous evidence, these results define a state of acute moderate hypoxia in which the whole fetus can sustain a relatively high rate of oxidative metabolism, and a state of acute severe hypoxia ([O2]a between 1.5 and 1.0 mM) in which O2 uptake by some fetal organs is selectively and markedly decreased.

Animals↗

PubMed1990

Uterine blood flow, oxygen and glucose uptakes at mid-gestation in the sheep.

In early ovine fetal development, the placenta grows more rapidly than the fetus so that at mid-gestation the aggregate weight of placental cotyledons exceeds fetal weight. The purpose of this study was to compare two separate methods of measuring uterine blood flow and glucose and oxygen uptakes in seven mid-gestation ewes, each carrying a single fetus. Uterine blood flow to both uterine horns was measured by microsphere and by tritiated water steady-state diffusion methodology. Calculations of tritiated water blood flows and oxygen and glucose uptakes were based on measurements of arteriovenous concentration differences across each uterine horn. The distribution of blood flow and oxygen uptake between the two uterine horns was strongly correlated with placental mass distribution. The two methods gave comparable results for uterine blood flow (457 +/- 35 vs 476 +/- 35 ml/min), oxygen uptake (457 +/- 35 vs 476 +/- 35 mumol/min), and glucose uptake (63 +/- 8 vs 64 +/- 6 mumol/min). Uterine blood flow was approximately 38% of the late gestation value and 56.1 +/- 1 times higher than umbilical blood flow. Uteroplacental oxygen consumption was about 58% of late gestation measurements and 3.9 +/- 0.5 times higher than fetal oxygen uptake. We confirm that the large placental mass of mid-gestation is associated with high levels of maternal placental blood flow and placental oxidative metabolism.

Animals↗

PubMed1989

Uptake of amino acids and ammonia at mid-gestation by the fetal lamb.

Fetal uptakes of amino acids and ammonia via the umbilical circulation were measured in single pregnant ewes at mid-gestation (range 66-81 days). There were significant net fluxes from placenta to fetus of ammonia and twelve amino acids (in decreasing order: glutamine, glycine, alanine, proline, lysine, arginine, threonine, valine, leucine, tyrosine, asparagine, isoleucine) and net fluxes from fetus to placenta of glutamate and serine. The estimated serine flux was 139 mumol day-1 (g fetal dry wt)-1. Comparison with late gestation data indicated a similar pattern of amino acid exchange. However, the relatively large placental uptake of fetal serine was a distinctive feature of mid-gestation. The net fetal uptake of amino acid nitrogen was 2.83 +/- 0.66 micrograms N (mumol O2 uptake)-1, or 18 mg N day-1 (g dry wt)-1. This uptake was similar in magnitude to the combined fetal requirements for nitrogen accretion and urea synthesis and represented approximately 32 and 43% of fetal carbon and energy requirements, respectively.

Amino Acids↗

PubMed1989

A comparison of amino acid arteriovenous differences across the liver and placenta of the fetal lamb.

Amino acid and ammonia concentrations as well as oxygen content were measured in either the right or left hepatic vein, the umbilical vein, and the umbilical artery in 13 fetal lambs in late gestation. There was an uptake of all of the essential and most of the nonessential amino acids by both lobes of the fetal liver. The umbilical venous-hepatic venous amino acid concentration differences were similar in the two hepatic lobes. While glutamine and glycine were taken up by both hepatic lobes, their metabolically related amino acids, glutamate and serine, were released by the fetal liver into the systemic circulation. There was a reciprocal net placental uptake from the umbilical circulation of glutamate and serine and a net fetal of glutamine and glycine, suggestive of interorgan cycling of these amino acids between the placenta and fetal liver. Total fetal umbilical nitrogen uptake was 0.91 g N.kg-1.day-1. The umbilical venous-hepatic venous differences of ammonia were positive and not significantly different in the two lobes. There was a significant umbilical uptake of ammonia (12.8 +/- 1.8 microM; 0.0078 microM NH3/microM O2). However, 0 the ratios of NH3 to O2 were much higher in each lobe (right, 0.060; left, 0.079; each P less than 0.01) than in the umbilical circulation.

Amino Acids↗

PubMed1989

Effect of umbilical blood flow on transplacental diffusion of ethanol and oxygen.

We studied the effect of varying umbilical blood flow (F) on transplacental diffusion of ethanol and O2 before and during partial occlusion of the fetal abdominal aorta. At steady state, samples of umbilical and uterine arterial and venous blood were drawn simultaneously from chronically indwelling catheters and analyzed for the concentration of ethanol. O2 capacity, O2 saturation, PO2, PCO2, and pH. A decrease in F from 507 to 289 ml/min (P less than 0.001) was associated with a significant (P less than 0.02) increase of the umbilical-uterine venous ethanol concentration difference. This increase was indicative of a 25% diffusional shunt for ethanol on the fetal side of the placenta. The decrease in F caused a decrease in the umbilical O2 delivery-to-control O2 uptake ratio from 3.1 to values between 2.2 and 0.8 and was associated with a decrease in fetal O2 uptake to values between 94 and 56% of control. Uterine venous PO2 increased in response to the decrease in fetal O2 uptake. Umbilical venous PO2 correlated with uterine venous PO2 (r = 0.8, P less than 0.02). The response of fetal O2 uptake to decrease in umbilical O2 delivery was nonlinear and confirmed previous studies, showing that the normal umbilical O2 delivery rate exceeds approximately twofold the minimum necessary to sustain a normal rate of fetal oxidative metabolism.

Animals↗

PubMed1989

Fetal neuromuscular blockade: effect on oxygen demand and placental transport.

To study mechanisms by which variations in fetal oxygen demand alter fetal oxygen saturation and PO2, we measured uterine and umbilical blood flow and transplacental oxygen diffusion rate in eight chronically prepared pregnant ewes before and during fetal neuromuscular blockade with pancuronium bromide (0.2 mg/kg). Uterine and umbilical blood flows were measured by applying the steady-state method using ethanol as the test substance. Fetal oxygen uptake decreased 7.5% (P less than 0.05). Umbilical blood flow increased 6% (P less than 0.05), whereas uterine blood flow did not change significantly. Fetal arterial oxygen saturation increased markedly (54.8-60.9%; P less than 0.001). There were also significant increases in umbilical vein oxygen saturation (83.6-86.9%; P less than 0.01), uterine vein oxygen saturation (70.7-72.2%; P less than 0.01), umbilical vein PO2 (29.4-32.1 Torr; P less than 0.001), and uterine vein PO2 (49.4-50.7 Torr; P less than 0.01). The uterine-umbilical venous PO2 difference decreased significantly (20.0-18.6 Torr; P less than 0.001), whereas there was no significant change in the uterine-umbilical venous PCO2 difference or in the umbilical ethanol shunt. The data indicate that follows a small decrease in fetal oxygen demand is caused by two aspects of placental oxygen transport: 1) umbilical and uterine blood flow do not react homeostatically to prevent the rise of PO2 in the placental circulation, and 2) the decrease in oxygen flux from placenta to fetus is associated with a decrease in the transplacental PO2 gradient.

Animals↗

PubMed1988

Ovine fetal response to water deprivation: aspects on the role of vasopressin.

The effect of maternal hyperosmolality as created by an acute mannitol infusion was evaluated in eight chronic sheep preparations. Fetal osmotic and haemodynamic responses were compared to those achieved during an arginine vasopressin (AVP) infusion into the fetus (approximately 400 microU/(min kg]. To assess the AVP sensitivity of the fetal kidney the urine osmolality was determined. The activity of adenylate cyclase was measured in placental cotyledons as an indicator of AVP receptors affecting water permeability. The maternal mannitol infusion induced an increase in fetal serum AVP levels from 1.18 +/- 0.25 up to 13.76 +/- 2.11 pg/ml. During the fetal AVP infusion the AVP levels were approximately 22 pg/ml, somewhat higher when given concurrently with a mannitol infusion to the ewe (peak value: 26.13 +/- 2.80 pg/ml). Fetal heart rate increased significantly during maternal hyperosmolality while this effect was blunted by exogenous AVP given to the fetus. The AVP infusion did not affect fetal or maternal serum osmolality. During the mannitol infusion fetal serum osmolality increased to peak values which were not significantly different whether or not AVP was infused into the fetus (from 298.0 +/- 0.85 to 309.0 +/- 0.90, and from 297.7 +/- 1.47 to 307.9 +/- 0.90 mosmol/kg, respectively). Similarly, there were no differences in the effect of mannitol infusion upon fetal urine osmolality with or without AVP infusion (increments: + 149.7 +/- 34.12 and + 148.7 +/- 31.30 mosmol/kg, respectively). Adenylate cyclase activity in the placenta was unchanged before and after AVP stimulation. The data suggest an unresponsiveness of placental water permeability to fetal AVP infusion. We also conclude that a maximal urine osmolality was reached already at AVP levels obtained after an osmotic maternal load whereas at AVP levels more than twice as high the cardiovascular effects were still AVP dose-dependent.

Animals↗

PubMed1988

Fetal nutrition.

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Female↗

PubMed1988

Placental oxygen transport in sheep with different hemoglobin types.

To study the effect of genetic differences in the maternal oxyhemoglobin dissociation curve on fetal O2 supply, we compared eight pregnant ewes homozygous for high O2 affinity hemoglobin (A) with eight pregnant ewes homozygous for low O2 affinity hemoglobin (B). Each ewe carried a single fetus. Fetal weights were not significantly different (A, 3,000 +/- 170 g; B, 3,070 +/- 270 g). The A ewes had significantly higher arterial O2 saturation (95 vs. 89.4%), uterine blood flow per kilogram of fetus (464 vs. 374 ml/min), uterine venous O2 saturation (78.1 vs. 67.5%), and placental-to-fetal weight ratio (0.107 vs. 0.085). Uterine venous PO2 was significantly less in A ewes (41.7 vs. 47.6 Torr), but umbilical venous and arterial PO2 and fetal O2 uptake were virtually equal in the two groups. We conclude that the difference in O2 affinity between A and B hemoglobins is fully compensated for by differences in arterial O2 saturation, in the rate of perfusion of the pregnant uterus, and in the degree of PO2 equilibration between the uterine and umbilical circulations so that the single fetuses of A and B hemoglobin carriers have equal levels of oxygenation.

Animals↗

PubMed1988

Measurement of blood flow and oxygen consumption in the pelvic limb of fetal sheep.

In order to determine blood flow and oxygen consumption in the pelvic limb of fetal sheep, we applied the Fick principle of measurement of oxygen consumption in seven paired experiments in seven fetal sheep under normal conditions and after treatment with pancuronium bromide. Catheterization procedures, which minimized interference with the study limb circulation, avoided changes of catheter tip position during fetal movements,n and prevented collateral circulation to and from tissues not located in the pelvic limb, were utilized. Blood flow through the external iliac artery was measured by means of a transit time ultrasonic method. Six sample sets for oxygen content were drawn from the external iliac artery and vein during 45-min control period and repeated after neuromuscular blockade. Normal oxygen consumption under these experimental conditions was determined to be 20.7 +/- 1.9 (mean +/- SEM) mumole.min-1.100 g-1. Neuromuscular blockade caused oxygen consumption to decrease significantly (P less than 0.01) by 12% to 18.1 +/- 2.1 mumole.min-1.100 g-1 and decreased the average coefficient of variation from 15 to 8%. The data demonstrate that spontaneous skeletal muscle activity accounts for a significant amount of oxygen consumption, the level of which can vary widely over brief periods of time. These results suggest that such tissues with significant spontaneous changes in metabolic activity require repeated blood flow measurements with simultaneous determination of substrate arteriovenous differences to best describe metabolism under normal conditions.

Animals↗

PubMed1987

Leucine disposal and oxidation rates in the fetal lamb.

To verify previous indirect evidence suggesting an important role of amino acids as substrates of fetal oxidative metabolism, leucine disposal and oxidation rates were measured in chronically catheterized fetal lambs during the last month of gestation. Under normal physiologic conditions the leucine oxidation rates were 6.43 +/- 1.02 mumol min-1 for fetuses with an average weight of 3.22 +/- 0.07 kg and comparable in magnitude to the fetal rate of leucine accretion. In seven animals studied before and during fasting, the fetal leucine oxidation rate increased with fasting from 5.8 +/- 1.0 to 10.8 +/- 1.3 mumol min-1. These data demonstrate that there is rapid oxidative degradation of leucine by the fetus and that the rate of this process increases in response to maternal fasting.

Animals↗

PubMed1987

Relation between metabolic rate and body size in the ovine fetus.

Objectives were to describe the relations between fetal oxygen consumption (VO2), vital organ weights and body weight in sheep during growth between mid gestation and term (about 147 d). Umbilical VO2 in conscious, single-pregnant ewes and fetal wet and dry body weights were measured at 73-97 d (n = 14) and at 119-141 d (n = 28) of gestation. Fetal wet and dry organ weights were related to body weights in an additional seven single-pregnant and eight twin-pregnant ewes at 73-140 d. Fetal VO2/kg wet weight decreased by 25% between mid and late gestation, whereas VO2/kg dry weight decreased by 56% and was paralleled by a similar decline in the relative aggregate weight of the vital organs (liver, kidneys, heart, brain). Log-log regression of VO2 on dry body weight, and of dry vital organ weight on dry body weight yielded coefficients of 0.73 +/- 0.02 and 0.66 +/- 0.01, respectively, suggesting that a decline in the relative growth of metabolically active organs explains much of the decline in weight-specific VO2 during fetal development.

Animals↗

PubMed1987

Fructose disposal and oxidation rates in the ovine fetus.

Fructose disposal and oxidation rates were measured in fetal lambs receiving a constant intravenous infusion of D-[U-14C]fructose. Approximately 60% of the infused tracer entered the placenta, but loss of fructose into the maternal circulation was negligible. Fructose was metabolized to lactate and CO2 in both the placenta and fetus, whereas there was no detectable conversion to glucose. In well-fed ewes the fetal disposal and utilization rates of fructose were 2.4 +/- 0.17 and 0.97 +/- 0.09 mg/min. kg, respectively. The umbilical excretion rate of CO2 originating from the oxidation of fetal fructose was 18.1 +/- 1.3 mumol/min. kg or 5.3% of total fetal CO2 production. This excretion rate is one-fifth of the CO2 excretion rate from fetal glucose carbon. In four ewes comparison of fructose metabolism in the fed and fasted states showed a significant decrease of fructose production and oxidation with fasting. Although fructose is present in high concentrations in the fetal blood of ungulates, its contribution to fetal oxidative metabolism is relatively small in comparison to glucose.

Animals↗

PubMed1987

Persistent fetal pulmonary hypoperfusion after acute hypoxia.

To determine the effects of duration of hypoxia on fetal pulmonary blood flow and vasoreactivity, we studied the response of the fetal pulmonary vascular bed before, during, and after prolonged (2-h) and more brief (30-min) exposures to acute hypoxia in 19 chronically instrumented unanesthetized fetal lambs. Left pulmonary arterial blood flow was measured by an electromagnetic flow transducer. Fetal PO2 was lowered by delivering 10-12% O2 to the ewe. During 2-h periods of hypoxia left pulmonary arterial blood flow decreased, and main pulmonary arterial and pulmonary vascular resistance increased. The increase in pulmonary vascular resistance was sustained throughout the 2-h period of hypoxia. After the return of the ewe to room air breathing, pulmonary vascular resistance remained elevated for at least 1 h despite the rapid correction of hypoxemia and in the absence of acidemia. In contrast, after 30 min of hypoxia, left pulmonary arterial blood flow, pulmonary arterial pressure, and pulmonary vascular resistance returned to base-line values rapidly with the termination of hypoxia. The persistent pulmonary hypoperfusion after 2 h of hypoxia was attenuated by alpha-adrenergic blockade and was characterized by a blunted vasodilatory response to increases in fetal PO2. When fetal PO2 was elevated during the posthypoxia period in the presence of alpha-blockade, pulmonary blood flow still remained unresponsive to increases in fetal PO2. We conclude that 2-h periods of acute hypoxia can decrease fetal pulmonary vasoreactivity, and we speculate that related mechanisms may contribute to the failure of the normal adaptation of the pulmonary circulation at birth.

Adrenergic alpha-Antagonists↗

PubMed1987

Effect of insulin on glucose/oxygen and lactate/oxygen quotients across the hindlimb of fetal lambs.

In order to determine whether insulin stimulates glucose uptake by the hindlimb tissue of the fetal lamb, we performed 7 paired, euglycemic glucose 'clamp' experiments in 7 chronically prepared fetal sheep. Four sample sets for oxygen content, glucose and lactate concentration were drawn from the external iliac artery and vein during a control period and repeated during a euglycemic, hyperinsulinemic 'clamp' period. Insulin was infused at constant rate (4 mU/min/kg) and the fetal arterial glucose concentration was maintained by variable glucose infusion. The glucose/oxygen quotient increased significantly: 1.05 +/- 0.07 (control) versus 2.02 +/- 0.16 (hyperinsulinemia). There was no change in lactate/oxygen quotient. The data demonstrate that with maximal insulin stimulation, fetal hindlimb tissues increase glucose uptake by 92% with no large change in lactate production, indicating a net accumulation of glucose carbon under these experimental conditions.

Animals↗

PubMed1987

Metabolic quotients and oxygen extraction across the uterus of the post-term pregnant rabbit under chronic steady-state conditions.

The extraction of oxygen by the uterus in the term rabbit has been found to be very high. During post-term pregnancy, the fetuses of the rabbit are approximately 40% larger, despite a reduction in placental weight of approximately 30%. The purpose of our study was to investigate the changes that occur in the maternal rabbit to allow survival of the fetus under these conditions. Post-term pregnancies were induced in 5 white New Zealand rabbits by injections of chorionic gonadotropin and progesterone on the 26th day of gestation. Catheters were placed surgically on day 28, and blood samples were taken daily from the femoral artery and uterine veins starting at day 31. Each sample was analyzed for pH, PCO2, PO2, oxygen capacity and saturation, glucose, beta-hydroxybutyrate, lactate and acetoacetate. Coefficients of extraction were calculated for oxygen and metabolic quotients were calculated for each substrate. These data are compared with those obtained for the term rabbit in previous studies. There was a significant increase in the coefficient of oxygen extraction in the post-term animals; however, the metabolic quotients across the uterus were not significantly different between the term and the post-term rabbit.

Animals↗