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G Meschia

Publications and source records attributed to G Meschia.

At least 37 records · Page 2Linked to original sources
PubMed1995

Main routes of plasma lactate carbon disposal in the midgestation fetal lamb.

The turnover rates of plasma lactate, normalized for O2 consumption rate, are higher in the fetus than in the adult. This occurs despite very low rates of fetal gluconeogenesis which preclude the recycling of lactate carbon into glucose. In an effort to establish the main routes of disposal of fetal plasma lactate, 12 midgestation ovine fetuses (age 74 +/- 1 days) were infused intravenously at constant rate with L-[U-14C]lactate for a 4-hour period. At the end of the infusion, the amounts of 14C retained by the fetus and by the placenta, and the distribution of the retained 14C in free and protein-bound amino acids and in lipids were measured. Of the total 14C infused, 17.0 +/- 1.4% was recovered in the placenta, 4.0 +/- 0.3% in the fetal liver, and 15.0 +/- 0.8% in the extrahepatic fetal tissues. Of the retained radioactive carbon, 45-57% was recovered in the free and protein-bound amino acid fractions and 11-17% in the lipid fractions. Approximately 90% of the 14C in the free amino acid fractions was present as glutamate/glutamine, serine, glycine, and alanine carbon. In conjunction with data on fetal CO2 production from lactate carbon, these results demonstrate that the main routes of fetal lactate disposal are oxidation and synthesis of nonessential amino acids and lipids.

Amino Acids↗
PubMed1994

Amino acid uptake by the fetal ovine hindlimb under normal and euglycemic hyperinsulinemic states.

As part of an effort to establish the contribution of different fetal organs to fetal amino acid metabolism, we measured in nine sheep fetuses the uptake of 27 amino acids by the hindlimb under normal conditions and conditions by euglycemic hyperinsulinemia. The fetal hindlimb is representative of nonvisceral tissues, which in the mature fetus account for approximately 70% of fetal weight and 30% of fetal O2 consumption. In the normal condition, there was a significant uptake of 21 amino acids for a net total nitrogen uptake of 132 +/- 21 mg N.day-1 x 100 g-1. The amino acids taken up by the fetal limb included alanine and glutamine. In addition, the fetal limb had significant glutamate and serine uptakes. Because glutamate flows from fetus to placenta and there is no fetal uptake of maternal serine, this indicates production and interorgan transport of these amino acids within the fetus. Insulin infusion significantly decreased the arterial concentration of every amino acid with the exception of cystathionine and significantly increased limb blood flow and glucose uptake. It significantly increased the limb uptake of alanine, asparagine, glycine, isoleucine, methionine, and tyrosine, decreased the uptake of aspartate, and produced no significant change in the net total nitrogen uptake, which remained similar to control (137 +/- 16 mg N.day-1 x 100 g-1).

Amino Acids↗
PubMed1994

Placental and fetal serine fluxes at midgestation in the fetal lamb.

Plasma serine disposal rate (DR), decarboxylation, and conversion to fetal plasma glycine by the placenta were measured in six fetal lambs at 72 +/- 1 days gestation. L-[1-13C]serine, L-[U-14C]serine, and 3H2O were infused over 3 h into the fetal circulation, the latter for measurement of uterine and umbilical blood flow. The fetal plasma serine DR was 8.7 +/- 1.0 mumol/min or 61.8 +/- 4 mumol.min-1.kg fetus-1. Approximately 90% of the DR represented placental uptake of fetal serine. There was no detectable release of fetal serine into the maternal circulation. The fetal arterial plasma glycine-to-serine enrichment ratio was approximately 0.30. The conversion rate of fetal serine to fetal plasma glycine by the placenta was 5.8 +/- 0.7% of the serine DR. Fetal and placental CO2 production from fetal plasma serine carbon was 1.9 +/- 0.4 and 1.2 +/- 0.4 mumol/min, respectively. Thus, at midgestation, there is a rapid fetoplacental serine exchange that constitutes most of the fetal plasma serine turnover. Placental conversion of serine to fetal glycine and serine oxidation together account for only 10% of the placental uptake of fetal serine.

Animals↗
PubMed1994

Glutamate metabolism in fetus and placenta of late-gestation sheep.

Glutamate is produced by the fetal liver and taken up by the placenta. To explore the functional meaning of this exchange, the disposal rate (DR), clearance, conversion to glutamine, and decarboxylation rate of fetal plasma glutamate were studied at 129 +/- 2 days of gestation in seven fetal lambs infused via a systemic vein with L-[2,3,3,4,4-2H5]glutamate and L-[1-14C]glutamate. In two experiments, L-[1-13C]glutamate was also infused. The mean glutamate DR and clearance were 11.9 +/- 1.3 mumol.min-1.kg-1 and 200 +/- 8 ml.min-1.kg-1, respectively. The placenta extracted 88.5 +/- 0.8% of the tracer glutamate carried by the umbilical circulation and contributed to 61.3 +/- 3.2% of the glutamate DR. Most of the 14C infused as L-[1-14C]glutamate was converted to 14CO2: 37 +/- 4% by the fetus and 41 +/- 6% by the placenta. Of the labeled glutamate taken up by the placenta, 6.2 +/- 1.5% was returned to the fetus as glutamine. The glutamine-to-glutamate enrichment ratio in fetal arterial plasma was 0.066 +/- 0.008. We conclude that fetal plasma glutamate has an exceptionally high clearance because the flux of glutamate into the placenta is virtually equal to umbilical glutamate delivery rate. The main pathway of fetal plasma glutamate disposal is oxidation by placental and fetal tissues. Placental conversion of glutamate to fetal glutamine is a relatively small component of the placental metabolism of fetal glutamate.

Animals↗
PubMed1993

Ovine fetal placental lactate exchange and decarboxylation at midgestation.

In a study of the metabolic implications of the large placental-to-fetal mass ratio that characterizes early fetal development, fetal plasma lactate disposal rate and CO2 production from fetal plasma lactate by fetus and placenta were measured in six midgestation (71-80 days) pregnant sheep. A constant fetal intravenous infusion of L-[U-14C]lactate and 3H2O was given to establish fetal steady-state lactate specific activity and to measure uterine and umbilical blood flows. Fetal and placental weights were 158.6 +/- 19.7 and 441.9 +/- 32.7 g, respectively. There was a significant net lactate flux into the uterine circulation (31 +/- 4.3 mumol/min, P < 0.01) but no measurable umbilical uptake. Fetal plasma lactate disposal rate was 21.2 +/- 2.7 mumol/min, approximately one-half of which represented fetal lactate flux into the placenta (9.9 +/- 1.9 mumol/min). The oxidation rate of tracer lactate carbon to 14CO2 by placenta plus fetus was 72.6 +/- 4.7% of the infused tracer and was fairly evenly distributed between the placenta and the fetus (42.4 +/- 3.9 vs. 30.3 +/- 2.2%). The midgestation placenta metabolizes and produces fetal plasma lactate at rapid and nearly equal rates. This contrasts with the late-gestation placenta, which makes a small contribution to fetal lactate disposal and is a major net source of fetal lactate.

Animals↗
PubMed1993

Alanine umbilical uptake, disposal rate, and decarboxylation rate in the fetal lamb.

Fetal plasma alanine disposal rate (DR) and decarboxylation rate were measured at 132 +/- 1 days gestation in nine fetal lambs infused with L-[1-14C]alanine via a brachial vein. In five experiments, L-[1-13C]alanine was added to the infusate. Using L-[1-14C]alanine, we found mean DR to be 15.5 +/- 1.8 mumol.min-1 . kg-1. DR was significantly correlated to both arterial plasma alanine and whole blood lactate concentrations. Placental uptake of fetal plasma alanine accounted for 19 +/- 4% of DR. Fetal and placental production of CO2 from the first carbon of alanine were 61 +/- 2 and 16 +/- 2% of DR, respectively, for a total uterine excretion of 77 +/- 3%. Net alanine flux from placenta to fetus was 5.2 +/- 0.5 mumol.min-1 x kg-1, which was less than fetal plasma alanine decarboxylation (9.4 +/- 1.2 mumol.min-1 x kg-1) plus fetal alanine accretion (2.4 mumol.min-1 x kg-1). Utilizing L-[1-13C]alanine, we found DR to be 14.2 +/- 0.8 mumol.min-1 x kg-1, not significantly different from the 14C data. We conclude that both the umbilical uptake of alanine from the placenta and fetal alanine synthesis contribute to fetal alanine supply and that oxidation is the main route of fetal plasma alanine disposal.

Alanine↗
PubMed1993

Fetal pH improvement after 24 h of severe, nonlethal hypoxia.

The accumulation of hydrogen ions in fetal blood when fetal oxygenation is acutely decreased suggests metabolic instability. However, in 6 chronically prepared fetal sheep whose arterial O2 content and pO2 were abruptly reduced and maintained at about 1.7 mM and 12.6 Torr, respectively, we observed a significant decrease in fetal arterial lactate concentrations and an increase in pH to normal values after 24 h of continuous hypoxia compared with values observed after 5 h. This demonstrates that fetal pH measurements may not detect prolonged intrauterine hypoxia.

Animals↗
PubMed1993

Metabolism and transport of maternal serine by the ovine placenta: glycine production and absence of serine transport into the fetus.

The present study compares the transplacental transport of L-[l-13C]serine and L-[l-13C]leucine in sheep. An in vivo preparation using twin gestations was set up such that the arterial circulation to one uterine horn, including its placenta and fetus, was infused with tracer serine and leucine while the umbilical circulations of both fetuses were sampled. Uterine and umbilical blood flows were measured in each horn. Plasma serine enrichments were 14.6 +/- 2.7% and 4.3 +/- 1.6% in the uterine veins draining the experimental and control horns, respectively. Fetal plasma leucine enrichments in the umbilical veins were 50 and 55% of the uterine venous enrichments in the control and experimental fetuses, respectively. By contrast, during 280 min of infusion, there was no detectable serine enrichment in either fetal circulation. However, significant plasma glycine enrichment was present in the fetal circulation of the experimental horn and venous glycine enrichments in the experimental horn were significantly greater than arterial glycine enrichments for both the umbilical (p < 0.02) and uterine (p < 0.001) circulations. We conclude that under conditions in which leucine transport is easily demonstrable there is no significant transplacental transport of maternal serine and that maternal plasma serine is used within the uteroplacental tissues for producing glycine, some of which is delivered into the fetal circulation.

Animals↗
PubMed1992

Fetal serine fluxes across fetal liver, hindlimb, and placenta in late gestation.

Eleven studies of fetal serine fluxes were performed in chronically catheterized fetal lambs by continuous infusion of [1-13C]- and [U-14C]serine into a fetal brachial vein. At tracer serine steady state, samples were collected from the fetal abdominal aorta, umbilical vein, fetal hepatic vein, and fetal femoral vein and from the maternal femoral artery and uterine vein. Analyses were performed for plasma serine and glycine concentration, for serine and glycine 13C mole percent enrichment, and for whole blood 14CO2 and O2 concentrations. Uterine and umbilical blood flows were also measured. The placenta had a significant net uptake of fetal serine (2.1 +/- 0.5 mumol.min-1.kg-1, P < 0.01). Fetal plasma serine disposal rate (DR) was 42.5 +/- 3.9 mumol.min-1.kg-1.CO2 production from decarboxylation of fetal plasma serine represented 7.9 +/- 0.5% of DR, or 10.1 +/- 1.2 mumol CO2.min-1.kg-1. Fetal plasma glycine enrichment was 59.7 +/- 4.9% of fetal plasma serine enrichment. There was a significant loss of tracer serine from the fetal circulation into the placenta accounting for approximately 45% of infused tracer. Fifteen percent of this was converted to glycine and released into the umbilical circulation. There was a significant uptake of tracer serine by both fetal liver and fetal hindlimb with a significant CO2 production by both sites with serine oxidation predominantly in the carcass. These results indicate a high fetal serine disposal rate in the lamb, with rapid fetoplacental serine exchange, resulting in a net uptake of fetal serine by the placenta.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Placental glucose transport in heat-induced fetal growth retardation.

In six ewes heat stressed from 39 to 125 days gestation and studied in a normothermic environment at 135 days, fetal and placental masses were less than in control sheep (1,645 vs. 3,112 and 149 vs. 356 g, respectively, P less than 0.01). Umbilical glucose uptakes (Rf,UP) were measured keeping maternal arterial plasma glucose at 70 mg/dl at spontaneously occurring fetal plasma glucose values (state A) and at two additional fetal glucose levels, to determine the transplacental glucose difference (delta) vs. Rf,UP relation. At normal delta of 49.2 mg/dl, Rf,UP was less in the experimental group (3.2 vs. 5.6 mg.min-1.kg fetus-1, P less than 0.05). Differences in placental perfusion and glucose consumption could not account for this result, thus indicating a reduced placental glucose transport capacity. In state A, fetal hypoglycemia enlarged significantly (P less than 0.01) the delta to 56.7 mg/dl and increased Rf,UP approximately 50% over the Rf,UP at a normal delta. In heat-induced fetal growth retardation, fetal hypoglycemia increases the flux of maternal glucose across a placenta with reduced glucose transport capacity.

Acid-Base Equilibrium↗
PubMed1992

Metabolic adaptation of fetal hindlimb to severe, nonlethal hypoxia.

To test the hypothesis that an important aspect of the fetal response to severe, nonlethal hypoxia is a relatively large reduction in oxidative metabolism and small increase in lactate production by organs whose O2 supply is selectively reduced, net fluxes of O2, glucose, pyruvate, lactate, and CO2 derived from fetal plasma lactate carbon [(CO2)PL] were measured across the hindlimb and umbilical circulations in six sheep fetuses before and at 200-260 min of hypoxia. During hypoxia, blood lactate reached a high but steady level (15.2 +/- 2.2 vs. 1.7 +/- 0.2 mM; P < 0.001). Hypoxia was induced by reducing uterine blood flow. Limb O2 uptake and (CO2)PL decreased (P < 0.01) and lactate output increased (P < 0.05) (-83.1 +/- 13.9, -28.6 +/- 5.0, and +35.7 +/- 13.7 nmol.min-1 x g-1, respectively), while pyruvate and glucose uptakes remained similar to control. The increase in limb glycolysis was approximately 10% of the value that would compensate for the decrease in oxidative energy metabolism. The ratio of limb O2 uptake to fetus O2 uptake decreased significantly (0.247 +/- 0.029 vs. 0.447 +/- 0.036; P < 0.01). In contrast to fetal limb (CO2)PL, fetal (CO2)PL did not decrease. During severe, nonlethal hypoxia, fetal survival depends on uneven and counterbalancing organ O2 uptake and lactate metabolism.

Adaptation, Physiological↗
PubMed1991

Measurement of leucine and alpha-ketoisocaproic acid fluxes in the fetal/placental unit.

Many investigators are now using stable isotopes in place of radioactive isotopes because of ethical considerations in human research. Our laboratory has had a long history in the development of an ovine model for the study of the physiological and biochemical changes during pregnancy. We wanted to extend some of the hypotheses and experimental protocols developed while using this model system to the human. As a first step in this process, we carried out infusions using a mixture of both 14C and 13C isotopes of the essential amino acid L-leucine. Results from this study showed that turn-over rates calculated using the two isotopes were equal within experimental error (8.99 +/- 0.45 and 8.97 +/- 0.52 mumol/kg.min, respectively). A key step in the development of the techniques for this study involved the use of tert.-butyldimethylsilyl derivatives for the amino acids. Because of the strong M-57 peak seen in the mass spectra of these compounds, we were able to use a relatively inexpensive Hewlett-Packard mass-selective detector for these determinations. Enrichments in triplicate measurements of the same sample had a precision of +/- 0.03%. Similar precision data were obtained in enrichment measurements of the keto acids derived from the amino acids. The combination of the speed of the analysis and the excellent precision have provided us with the opportunity to study uptake and loss across an organ system (i.e. placenta, liver, etc). This tool is now being used to study the detailed flow of amino acids across the placenta during both normal and abnormal pregnancies.

Animals↗
PubMed1991

Glycine turnover and oxidation and hepatic serine synthesis from glycine in fetal lambs.

[1-13C]- and [1-14C]glycine were infused into chronically catheterized fetal lambs via a brachial vein. At tracer glycine steady state, samples were collected from the fetal abdominal aorta, umbilical vein, and fetal hepatic vein and from the maternal femoral artery and uterine vein. The samples were analyzed for plasma glycine and serine, for glycine and serine 13C atom% excess (APE), and for whole blood 14CO2 and O2 concentrations. Fetal plasma glycine disposal rate (DR) was 12.4 +/- 0.8 mumol.min-1.kg fetus-1.CO2 production from decarboxylation of fetal plasma glycine was 1.63 +/- 0.16 mumol.min-1.kg fetus-1 and represented 12.3 +/- 0.7% of DR. Approximately 50% of infused tracer glycine was taken up by the fetal liver with the release of labeled serine and CO2 in the fetal circulation. There was no detectable efflux of tracer glycine from the placenta into the maternal circulation. The tracer production of serine and CO2 accounted for 23 and 17%, respectively, of the hepatic tracer glycine uptake. The labeled CO2 released by the liver was a large fraction (approximately 70%) of the labeled CO2 produced by the fetus. The serine-to-glycine APE ratio in fetal plasma was approximately 5%. These results indicate that the fetal liver is the major site of fetal plasma glycine decarboxylation and of serine synthesis from plasma glycine.

Animals↗
PubMed1991

Effect of occluding one umbilical artery on placental oxygen transport.

Placental O2 transport was studied in seven fetal lambs before and after occluding one of the two umbilical arteries. Ethanol was used to measure uterine and umbilical blood flows using the steady-state transplacental diffusion method. Blood samples were drawn from umbilical artery, umbilical vein, both uterine veins, and maternal artery and analyzed for blood flow indicator, O2 content, PO2, PCO2, and pH. Occlusion reduced the placental mass and the uterine blood flow, which was available for transplacental exchange, to 49.5 and 46.5% of control, respectively. After occlusion, fetal blood pressure increased 38%, total umbilical blood flow decreased 25%, total fetal O2 uptake decreased 26%, fetal blood flow to the unoccluded placenta increased 52%, and the O2 flux from unoccluded placenta to fetus increased 49%. This increased flux was accompanied by a decrease in the PO2 of maternal venous blood from the unoccluded placenta and an enlargement of the transplacental PO2 gradient, resulting in a marked drop in umbilical venous PO2 (28.3 to 17.7 Torr). This evidence supports the hypothesis that placental O2 diffusing capacity is a limiting factor in placental O2 transport and agrees with other studies indicating the absence of homeostatic mechanisms for preventing acute changes of PO2 in the placental circulation.

Animals↗
PubMed1991

Gestational maturation of placental glucose transfer capacity in sheep.

The net transfer rate of glucose to the fetus from the placenta (Rf,up) increases approximately 10-fold over the second half of pregnancy. To examine the mechanism underlying this increase, we measured Rf,up at different glucose concentration gradients between maternal arterial (GA) and umbilical arterial (Ga) glucose and at three fetal ages: midgestation (76.0 +/- 0.6 days, n = 6), late gestation (131.5 +/- 2.1 days, n = 8), and an intermediate age (103.3 +/- 1.9 days, n = 4). The GA -- Ga gradient was varied by changing Ga below and above control values with fetal insulin and glucose infusions, respectively, while GA was kept constant at 70 +/- 2 mg/dl by a glucose clamp procedure. The slope of the line relating Rf,up to GA -- Ga increased from 0.15 to 1.01 dl/min in the 76- to 131.5-day period, while the intercept in the GA -- Ga axis remained approximately constant at 34 mg/dl. This indicates a fivefold increase in the ability of the placenta to supply glucose to the fetus at fixed values of maternal and fetal glucose concentration (placental glucose transfer capacity). Concomitant with this increase, there was a significant (P less than 0.001) decrease in control Ga from 26.7 +/- 1.3 to 20.3 +/- 0.3 mg/dl, leading to a significant increase in the GA -- Ga gradient and an 11-fold increase in control Rf,up (from 1.53 to 16.77 mg/min). We conclude that, in the second half of pregnancy, fetal glucose demand grows much more rapidly than placental glucose transfer capacity and requires a decrease in fetal glucose concentration to balance glucose supply and demand.

Animals↗
PubMed1991

Role of the circulation in measurement of lactate turnover rate.

Previous studies have shown that venous lactate specific activity during arterial tracer lactate infusion differs from arterial lactate specific activity during systemic venous tracer lactate infusion. We performed paired experiments on chronically catheterized rabbits to compare left ventricular (LV) infusion with femoral venous (FV) infusion of L-[U-14C]lactate. Blood was sampled from both the femoral artery (FA) and right ventricle (RV) during both modes of infusion. The mean lactate specific activity measured for each combination (infusion site, sampling site) was (FV,FA) 4,380 +/- 452, (FV,RV) 4,370 +/- 471, (LV,FA) 4,364 +/- 239, and (LV,RV) 3,325 +/- 240 (SE) dpm/mumol. Lactate turnover calculated from the specific activity in the (LV,RV) mode was significantly higher than from the other three modes (P less than 0.001). Models of lactate turnover are discussed demonstrating that the (FV,FA) and analogous modes of infusion sampling measure the turnover rate of lactate molecules that cycle through the circulation. This estimate of turnover is less than the turnover rate by the whole organism to the extent that some produced lactate is metabolized locally without entering the general circulation. The turnover calculated by the (LV,RV) mode overestimates the turnover of circulating lactate and relates to whole body lactate turnover in a complex manner.

Animals↗