Biomedical subjects

G Meschia

Publications and source records attributed to G Meschia.

At least 73 records · Page 4Linked to original sources

PubMed1987

Ontogenetic changes in the rates of protein synthesis and leucine oxidation during fetal life.

Studies of fetal leucine metabolism and protein synthetic rate, using L-(1-14)leucine as tracer, were carried out in 12 pregnant ewes at midgestation and compared with similar studies in late gestation. The disposal rate of fetal plasma leucine ranged between 3.07 and 9.06 mumol/min and was correlated (r = 0.89) to fetal dry weight. The fluxes to CO2 excretion and to protein synthesis were 18.6 +/- 2.6 and 37.2 +/- 2.6% of disposal rate, respectively. The flux of leucine molecules into the placenta was relatively large and correlated to the placental/fetal dry weight ratio (r = 0.84). The mean fractional protein synthetic rate was 0.216 +/- 0.01 day-1. Comparison with late gestation data showed that fractional protein synthetic rate is inversely correlated (r = 0.87) to gestational age and that fetal protein synthetic rate (PRs, g/day) is related to fetal dry weight (DW,g) by the allometric equation: log PRs = -0.503 + 0.754 log DW The 0.754 exponent is similar to the exponent relating fetal oxygen consumption to dry weight (0.729). This indicates that protein synthesis and energy metabolism per g dry weight decrease during fetal growth at approximately the same rate so that the protein synthesis/oxygen consumption ratio tends to remain constant.

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PubMed1987

Some aspects of placental function in chronically heat-stressed ewes.

Pregnant ewes were exposed continuously to high ambient temperature (38-40 degrees C for 9 h, 30-32 degrees C for 15 h daily, relative humidity 40-50%) between about 45 days and 120 days of gestation and studied at 132-137 days. Results were compared with those of ewes of similar gestational age which were not exposed to heat at any stage of pregnancy. Heat exposure did not depress appetite but caused variable reductions in placental weight. Fetal weight was reduced to a lesser extent and correlated with placental weight. Uterine and umbilical blood flows and placental glucose transfer capacity were all significantly reduced and highly correlated with placental weight. These effects were accompanied by an enlargement of the PO2 difference between uterine and umbilical venous blood, a decrease in the PO2 and oxygen saturation of fetal arterial blood, and fetal hypoglycemia. Uteroplacental rates of oxygen and glucose utilization and the concentration of fructose in fetal blood were each significantly correlated with placental weight. It is suggested that reduced placental growth is a primary effect of chronic maternal heat stress and that the associated retardation of fetal growth represents a fetal adaptation to a decreased placental ability to supply oxygen and nutrients.

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PubMed1986

Time-dependent response of fetal pulmonary blood flow to an increase in fetal oxygen tension.

We describe the temporal characteristics of the response of the fetal pulmonary circulation to the vasodilatory stimulus of a sustained increase in fetal PO2 (5.1 +/- 0.7 Torr) in 13 chronically prepared fetal sheep. Left pulmonary artery blood flow was measured by electromagnetic flow transducer. Fetal PO2 was increased by delivery of 100% oxygen to the ewe and did not significantly change during the 2 h period of oxygen administration. Fetal left pulmonary artery blood flow slowly increased to a peak approximately 2.7 times the control value 40-50 min after the onset of increased PO2. It then steadily declined toward baseline over the next hour of increased PO2. Maximal pulmonary blood flow in response to the increase in PO2 increased with gestational age. Pulmonary arterial, aortic, and left atrial blood pressures did not change significantly in the animals in which measurements were made. We conclude that the changes in fetal pulmonary blood flow with increased fetal PO2 depend upon the time after the PO2 is increased. The adaptation seen during the second hour suggests the existence of mechanisms that tend to keep the fetal pulmonary circulation chronically constricted at any PO2 likely to be encountered in fetal life.

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PubMed1986

Metabolic and circulatory studies of fetal lamb at midgestation.

Uterine and umbilical blood flows, the placental clearance of 3H2O, uterine and umbilical uptakes of oxygen, glucose, and lactate were measured in conscious, pregnant sheep at 71-81 days gestation. Fetal weight was 210 +/- 20 g and less than half placental weight. In relation to fetal weight, umbilical flow was 468 +/- 57 ml X min-1 X kg-1, more than double normal values for the mature fetus. Clearance of 3H2O was approximately 12% of the late pregnancy value but high in relation to fetal weight (280 +/- 23 ml X min-1 X kg-1). Fetal oxygen uptake was 10.9 +/- 0.6 ml X min-1 X kg-1, approximately 40% greater than in late gestation. Umbilical uptake of glucose was also relatively high, whereas lactate uptake was low. Uteroplacental tissues consumed more than 80% of the oxygen and glucose taken up by the pregnant uterus. However, uteroplacental utilization rates of oxygen and glucose as well as net lactate production were lower (approximately 50, 30, and 25%, respectively) than in late pregnancy, despite a larger placental mass (486 +/- 22 vs. 302 +/- 12 g).

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PubMed1985

Uterine and whole body oxygen extractions in the pregnant rabbit under chronic steady-state conditions.

Seventeen pregnant rabbits were studied under conscious, unstressed conditions after catheterization of the right ventricle (RV), a femoral artery (A), and a uterine vein (UV). Respiratory gas tensions, pH, and oxygen saturations and contents were determined serially throughout the latter half of gestation. The uterine coefficient of oxygen extraction increased with gestational age (R = 0.86) and became 60.6% +/- 0.3% during the last 4 days of pregnancy. To compare uterine perfusion with whole body perfusion in relationship to oxygen demands, the (Ao2 - UVo2/Ao2 - RVo2) ratio was computed. The ratio was greater than or equal to 1 after 20 days of gestation, which demonstrated that in regard to oxygen demands the rabbit uterus is relatively underperfused compared to the rest of the maternal organism in the last part of pregnancy. A comparison with analogous data in other species demonstrates that the pregnant rabbit, like the guinea pig, has a much lower rate of uterine blood flow than does the pregnant sheep. These interspecies differences in the perfusion rate and oxygen extraction of the pregnant uterus are related to differences in placental structure.

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PubMed1985

Cardiac output distribution and uteroplacental blood flow in the pregnant rabbit: a comparative study.

This study presents data on cardiac output distribution and uterine and placental blood flows in pregnant rabbits under chronic steady-state conditions. Ten liters and 67 fetuses were studied at 29 days of gestation, by means of radioactive microspheres. Five nonpregnant female animals were also studied for comparison. Mean cardiac outputs were 747.16 +/- 55.7 and 613.80 +/- 63.76 ml/min in the pregnant and nonpregnant states, respectively. In the pregnant animals, uterine and mammary blood flows were 6.7% +/- 0.7% and 5.1% +/- 0.5% of cardiac output, respectively. Within litters, the highest placental blood flows occurred at the ovarian and vaginal ends of the uterine horn. Placental blood flow per gram of fetus was 0.106 +/- 0.008 ml X min-1 X gm-1. A comparison with analogous data in the guinea pig and sheep demonstrates that toward the end of pregnancy placental blood flow per gram of fetus is approximately 2.5-times higher in sheep than in rabbits and guinea pigs. Expressed as a percentage of cardiac output, near-term uterine blood flow is significantly less in rabbits than in guinea pigs and sheep, whereas mammary blood flow is significantly higher. These interspecies differences are related to differences in placental structure, fetal/maternal mass ratio, and maturity at birth.

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PubMed1985

Relationship between metabolic rate and body size in fetal life.

To define the O2 consumption rate (VO2) versus body mass relation during fetal growth, we compared fetal sheep VO2 at mid and late gestation. VO2 per kg wet weight was 37% higher at mid gestation. However, VO2 per kg dry weight was 2.5 times higher, and associated with a high viscera/body weight ratio. Fetal VO2 tends to grow proportionally to body mass because marked decreases in the relative growth of visceral organs and in the VO2/dry weight ratio are accompanied by a decrease in body water.

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PubMed1985

Effect of insulin on glucose uptake in near-term fetal lambs.

Glucose clamp experiments were performed in 27 chronically catheterized, late-gestation fetal lambs in order to measure the effect of fetal insulin concentration on fetal glucose uptake at a constant glucose concentration. Fetal arterial blood glucose concentration was measured over a 30-min control period and then maintained at the control value by a variable glucose infusion into the fetus while insulin was infused at a constant rate into the fetus. Plasma insulin concentration increased from 21 +/- 10 (SD) to 294 +/- 179 (SD) microU X ml-1. The exogenous glucose infusion rate necessary to maintain constant glycemia during the plateau hyperinsulinemia averaged 4.3 +/- 1.6 (SD) mg X min-1 X kg-1. In a subset of 13 animals, total fetal exogenous glucose uptake (FGU; sum of glucose uptake from the placenta via the umbilical circulation plus the steady-state exogenous glucose infusion rate) was measured during the control and hyperinsulinemia period. FGU was directly related to insulin concentration (y = 4.24 + 0.07x) at insulin levels less than 100 microU/ml and increased 132% above control at insulin levels above 100 microU/ml. Hyperinsulinemia did not affect fetal glucose uptake from the placenta via the umbilical circulation. These studies demonstrate that insulin concentration is a major factor controlling glucose uptake in the near-term fetal lamb, and that an increase of fetal insulin does not affect the transport of glucose to the fetus from the placenta.

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PubMed1985

Safety margin of fetal oxygenation.

The supply of O2 to fetal tissues depends upon a balance between factors that favor and hinder fetal oxygenation. Experiments in sheep have demonstrated that high rates of placental perfusion, high O2 affinity of fetal red cells and high rates of perfusion in fetal tissues compensate for an ineffective placental exchange system and for the circulatory arrangement by which fetal arterial blood is formed by mixing oxygenated umbilical venous blood with deoxygenated systemic venous blood. Under normal physiologic conditions the balance of the factors that influence fetal oxygenation provides the fetal lamb with an oxygen supply approximately twice the minimum level necessary to sustain fetal life.

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PubMed1985

The relationship of umbilical glucose uptake to uterine blood flow.

In 30 experiments performed on 5 pregnant sheep, the rate of glucose transfer from the placenta to fetus via the umbilical circulation was measured while varying uterine blood flow by means of a cuff-type occluder and while maintaining a constant maternal glucose concentration by means of a 'glucose clamp'. Over the range of uterine blood flows obtained, there was no significant effect on the simultaneously measured umbilical blood flow. Fetal glucose uptake and arterial glucose concentration remained normal as the uterine blood flow rate decreased from 600 to 300 ml per min per kg of fetus. At blood flow rates less than 300 ml.min-1.kg-1, the fetal glucose uptake decreased and became negative in one instance while the arterial glucose concentration became variable and markedly increased in 2 animals. This increase in fetal glucose concentration was associated with a decrease in the uterine oxygen delivery rate, a decrease in fetal oxygen content and a decrease in fetal oxygen uptake. These observations support the concept that fetal glucose metabolism is altered by severe hypoxia and demonstrate that there is little effect of uterine blood flow on fetal glucose uptake in the normal physiological range.

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PubMed1984

Comparison of fetal and maternal hind limb metabolic quotients in sheep.

This study compared substrate utilization by the fetal hind limb and the maternal hind limb in 26 sheep at 120 to 135 days of gestation. Catheters were placed in the mother and the fetus to sample femoral arterial and venous blood by use of a nonocclusive technique. Arterial and venous concentrations of oxygen content, glucose, lactate, acetate, and ketoacids were measured simultaneously and were used to calculate metabolic quotients. The fetal hind limb was perfused with arterial blood having a lower oxygen content than the maternal hind limb (3.03 +/- 0.17 versus 4.94 +/- 0.24 mmol/L, p less than 0.001) and had a smaller arteriovenous difference of oxygen content (0.97 +/- 0.05 versus 2.68 +/- 0.104 mmol/L, p less than 0.001). Despite a lower fetal arterial glucose concentration (0.81 +/- 0.05 versus 2.58 +/- 0.13 mmol/L, p less than 0.001), the glucose/oxygen quotient (0.82 +/- 0.05 versus 0.20 +/- 0.02, p less than 0.001) and the arteriovenous difference of glucose (0.13 +/- 0.01 versus 0.08 +/- 0.01 mmol/L, p less than 0.001) were higher in the fetal hind limb than in the maternal hind limb. Both limbs were net producers of lactate. The (glucose + lactate)/oxygen quotient was also higher in the fetal hind limb than in the maternal hind limb (0.68 +/- 0.05 versus 0.12 +/- 0.04, p less than 0.001). In the maternal hind limb, acetate and ketoacids uptake could account for 48% +/- 6% of total oxygen consumption whereas in the fetal hind limb it accounted for only 12% +/- 4% (p less than 0.001). The data demonstrate that, in relation to oxygen uptake, fetal hind limbs have approximately a 2.8% higher rate of perfusion and take up approximately four times as much glucose as the hind limbs of the mother in the resting state.

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PubMed1984

Fetal glucose uptake and utilization as functions of maternal glucose concentration.

Seventeen studies were performed in 12 pregnant sheep to examine the relationship among simultaneously measured glucose uptake via the umbilical circulation, fetal glucose utilization (mg X min-1 X kg-1), and maternal arterial glucose (Gm, mg/dl). Fetal glucose utilization was measured by means of tracer glucose infused into the fetus or both mother and fetus. By fasting the ewe, Gm was varied in the 62-22 range. A decrease in Gm was accompanied by a significant (P less than 0.001) decrease in umbilical uptake (uptake = 0.09 Gm - 0.96, r = 0.82) and in fetal utilization, measured either by [U-14C]glucose (utilization = 0.062 Gm + 0.91, r = 0.90) or [6-3H]glucose (utilization = 0.065 Gm + 0.51, r = 0.91). At uptake greater than 3 mg X min-1 X kg-1, utilization and uptake were not significantly different. At lower uptakes, utilization did not decline as much as uptake. The results demonstrate that maternal fasting decreases both the umbilical uptake and the fetal utilization of glucose and suggest that fetal glucogenesis increases when the availability of exogenous glucose is markedly reduced.

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PubMed1984

Maternal-fetal glucose exchange: necessity of a three-pool model.

Tracer glucose was infused simultaneously into mother ( [6-3H]glucose) and fetus ( [U-14C]glucose) in pregnant sheep in the last month of gestation to study the exchange of glucose molecules between maternal and fetal blood. Net rates of entry and exit of tracer glucose via the uterine and umbilical circulations were measured by application of the Fick principle under steady-state conditions. The net flux of fetal tracer to the uteroplacenta from the fetus was 53.4 +/- 3.1% of the fetal tracer infusion. The net flux of fetal tracer into maternal blood was 43.8 +/- 5.0% of the net flux of fetal tracer to the uteroplacenta from fetal blood. The net flux of maternal tracer to the uterus from the mother was 31.7 +/- 2.8% of the maternal tracer infusion. The net flux of maternal tracer into fetal blood was 40.5 +/- 4.4% of the net flux to pregnant uterus from maternal blood. This evidence demonstrates that the uteroplacental tissue mass constitutes a glucose pool that is interposed between the maternal and fetal glucose pools and rapidly metabolizes glucose molecules derived from both maternal and fetal blood. Calculations based on a three-pool model show that the fetal glucose pool contributes approximately 40% of the glucose that is metabolized by the placenta. The comparison of the three-pool model with a previously proposed two-pool reversible model shows that the latter lumps the placental utilization of fetal glucose with fetal glucose utilization and overestimates the rate of fetal glucose metabolism by approximately 60%.

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PubMed1984

Effect of insulin on glucose uptake by the maternal hindlimb and uterus, and by the fetus in conscious pregnant sheep.

Previous studies have demonstrated the presence of insulin receptors on the maternal surface of the placenta in several species and the specific binding of insulin to the placenta in sheep. However, both in-vitro and in-vivo studies have produced conflicting evidence concerning the effect of insulin on placental glucose uptake. To clarify this problem, we measured maternal hindlimb, uterine and fetal glucose and oxygen extractions and glucose/oxygen quotients in chronically catheterized, non-stressed, late-gestation pregnant sheep over 1 h at a constant concentration of arterial plasma glucose, and again during the next 2 h at the same glucose level but at a higher insulin concentration using glucose 'clamp' methodology. Insulin produced a 4.9-fold increase in glucose extraction and a 3.5-fold increase in glucose/oxygen quotient across the hindlimb; in contrast, insulin did not significantly affect uterine or fetal glucose extraction or glucose/oxygen quotient. We conclude that in contrast to other tissues of the pregnant ewe, placental glucose uptake and transfer are insensitive to variations in maternal insulin concentration.

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PubMed1984

Fetal CO2 kinetics.

Knowledge of CO2 kinetics in the fetus is important for the design and interpretation of fetal metabolic studies that use carbon-labelled tracers. To study fetal CO2 kinetics, four fetal sheep were infused at constant rate with NaH14CO3 to simulate a constant rate of fetal 14CO2 production from the metabolism of a 14C-labelled substrate. Uterine and umbilical blood flows, and concentrations of 14CO2 and total CO2 in umbilical arterial and venous blood and in uterine arterial and venous blood were measured. During steady state, the excretion of 14CO2 via the umbilical circulation was 99.6 +/- 1.0 (SEM)% of the NaH14CO3 infusion rate. The irreversible disposal rate of CO2 molecules from the fetal CO2 pool was approximately 5 times greater than the metabolic production of CO2 by the fetus. This evidence demonstrates that measurements of fetal 14CO2 excretion via the umbilical circulation can provide an accurate measurement of fetal 14CO2 production and that the exchange rate of CO2 molecules between placenta and fetal blood is much greater than the net rate of excretion of CO2 molecules from fetus to placenta.

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PubMed1984

Non-steady state placental transfer of highly diffusible molecules.

In twelve experiments performed on five pregnant sheep, uterine and umbilical venous blood samples were drawn in rapid succession following the beginning of a maternal arterial infusion of ethanol and antipyrine. Within a 20 s period the uterine venous ethanol/antipyrine concentration ratio increased from a minimum of 0.3 to 0.7 and the umbilical venous ethanol/antipyrine concentration ratio decreased from a maximum of 3 to 1.2. These results are in agreement with a model of placental exchange showing that the transfer rate of highly diffusible molecules is permeability limited at the beginning of the infusion and then rapidly becomes blood flow limited as the diffusing solutes accumulate in the placenta. The demonstration that the placental barrier is more permeable to ethanol than antipyrine, concomitant with previous demonstrations that the steady state placental clearances of ethanol and antipyrine are nearly equal, supports the hypothesis that in the steady state, the placental clearance of ethanol is blood flow limited.

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PubMed1983

Partition of maternal nutrients to the placenta and fetus in the sheep.

Utilizing the Fick Principle, the fluxes of oxygen and glucose leaving the uterine circulation and entering the fetal umbilical circulation were measured simultaneously in 35 chronically catheterized sheep. Additionally, the distribution of placentally produced lactate into the uterine and umbilical circulations was measured by the same techniques. Under unstressed conditions, placental oxygen consumption accounted for approximately half the oxygen exiting the uterine circulation. Placental glucose consumption averaged 75% of the glucose exiting the uterine circulation, and this proportion increased with decreasing glucose concentration in the maternal artery. Lactate was produced at a high rate by all placentae, and distributed disproportionately to the fetus, in spite of higher fetal lactate concentration. Fetal metabolism was aerobic, as demonstrated by a high rate of net oxygen consumption and a high rate of net lactate consumption. Fetal oxygen metabolism correlated well with fetal weight and with the sum of net fetal lactate and glucose consumption.

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PubMed1983

Partition of maternal glucose production between conceptus and maternal tissues in sheep.

Experiments were conducted in late-gestation, conscious, pregnant ewes to measure maternal glucose production and the net glucose uptake by the uterus, fetus, uteroplacenta, and nonuterine maternal tissues. Glucose concentration in the ewes varied naturally or decreased in response to fasting. Normoglycemic ewes (63.8 +/- 8.7 mg/dl) had a glucose production rate of 178.7 +/- 44.5 mg/min compared with a rate of 76.9 +/- 20.6 mg/min for hypoglycemic ewes (34.7 +/- 7.4 mg/dl). Uterine glucose uptake (56.5 +/- 16.8 mg/min), fetal glucose uptake (15.7 +/- 5.2 mg/min), uteroplacental glucose uptake (40.8 +/- 13.4 mg/min), and nonuterine maternal glucose uptake (122.2 +/- 27.7 mg/min) in the normoglycemic ewes were significantly greater than in the hypoglycemic ewes (28.7 +/- 5.4, 7.5 +/- 4.4, 21.2 +/- 6.6, and 48.2 +/- 15.2 mg/min, respectively). The fractional distribution of maternally produced glucose among nonuterine maternal tissues, the fetus, and the uteroplacenta was not altered markedly by hypoglycemia despite a 57% reduction in maternal glucose production.

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