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Biomedical subjects

G Meschia

Publications and source records attributed to G Meschia.

At least 109 records · Page 6Linked to original sources

Placental transfer of glucose.

The rates of glucose transfer from maternal blood to pregnant uterus and from placenta to fetus were measured in eight sheep at spontaneously occurring glucose concentrations (control state) and while the fetus, the mother, or both were receiving a constant infusion of glucose. In addition two fetuses received insulin infusions. In the control state the net glucose flux from placenta to fetus was only 27 +/- 2.6% (SEM) of the net flux from the uterine circulation to the pregnant uterus. An empirical equation describing the relationship between placental glucose transfer and arterial plasma glucose concentrations was derived from the data and compared with equations constructed on the basis of methematical models of placental function. This analysis indicates that: (1) placental glucose transfer is mediated by carriers with Km approximately equal to 70 mg/dl; (2) the rate of glucose transfer from mother to fetus is limited primarily by the transport characteristics and glucose consumption rate of the placenta; (3) under normal conditions of placental perfusion, glucose transfer is approximately 15% less than it would be if placental blood flows were infinitely large.

Animals↗

Uterine uptake of amino acids and placental glutamine--glutamate balance in the pregnant ewe.

The uterine uptake of amino acids was studied in 10 pregnant sheep with gestational ages of 114-146 days. After recovery from surgery, arterial and uterine venous samples were drawn simultaneously via indwelling catheters and analysed for amino acid and oxygen content. In seven ewes, amino acid concentrations were measured by a chromatographic technique. In four ewes, glutamate and glutamine arterio-venous differences across the uterine and umbilical circulations were measured by an enzymatic method. The uptake of neutral and basic amino acids was 66 mumol/mmol O2 and 17.3 mumol/mmol O2, respectively. Comparison of uterine and umbilical uptake shows that the bulk of the neutral and basic amino acids taken up by the pregnant uterus are transferred to the fetus. there was no significant uptake of acidic amino acids (i.e. glutamate, aspartate and taurine). glutamate was delivered from the fetus to the placenta but excretion of glutamate into the uterine circulation was negligible. Glutamine and asparagine were delivered to the fetus in amount which were two to three times larger than the placental uptake of glutamate and aspartate. Therefore placental conversion of exogenous glutamate and aspartate to glutamine and asparagine cannot account entirely for the fetal uptake of these amino acids.

Amino Acids↗

Evolution of thinking in fetal respiratory physiology.

An outstanding characteristic of intrauterine life is the low oxygen pressure (Po2) of fetal blood. It seemed at one time that in order to tolerate the Po2 of the uterine environment the fetus must have a relatively slow rate of oxidative metabolism or depend upon anaerobic pathways of substrate utilization. Subsequent studies have shown that the fetus has a high rate of oxygen consumption and that lactic acid is a substrate rather than a net product of normal fetal metabolism. The circulatory response of the fetus to acute hypoxia is centered on the requirement of maintaining the arterial oxygen flow to the heart and central nervous system without increasing cardiac output. The arterial oxygen flow concept helps in understanding the physiologic meaning of the high oxygen affinity of fetal blood and the boundary conditions of the fetal defense against hypoxia.

Animals↗

Changes in cervical compliance at parturition independent of uterine activity.

A new animal model has been developed to measure intrinsic changes of cerivcal compliance during spontaneous parturition or exposure to hormonal manipulation. Intermittent measurements of cervical compliance and continous measurements of uterine and cervical pressure were made during the last month of gestation of nine pregnant ewes. Cervical compliance increased abruptly and dramatically during spontanous and dexamethasone-induced parturition. Maternal progesterone supplementation at parturition inhibited uterine contractions but not the increase in cervical compliance, demonstrating the independence of the two events. The cervix was found to contract rhythmically and vigorously with a gradual decrease in activity as parturition approached.

Animals↗

Insulin secretion in fetal and newborn sheep.

The relationships between arterial plasma insulin, glucose, and fructose concentrations during the fed and fasted state were studied in seven fetal lambs and their mothers. A significant correlation between insulin and glucose concentration was noted in all fetal lambs and in their mothers. Fetal sensitivity to glucose, as measured by the slopes of the insulin-response curves, was equal to that of the adult although the fetal response was shifted to the left of the maternal. Glucose infusion in four fetal lambs caused significant insulin elevations but no early insulin response (phase I). Maternal fasting caused no alteration in glucose-induced response in the fetus. Similar glucose infusions in newborn and 1-mo-old lambs demonstrated significant early-phase insulin secretion. Basal insulin to glucose ratios were consistent with an adult pattern as early as 3 days after birth.

Animals↗

Regulation of cerebral blood flow in the ovine fetus.

The effects on fetal cerebral blood flow (Qc) of changes in the carotid arterial and sagittal sinus venous PO2, PCO2, and oxygen content were studied in the chronically catheterized ovine fetus in utero at 130-140 days of gestation. Forty-seven measurements of Qc were made in 20 fetuses with radioactive microspheres. In 11 of these animals, 84 measurements of cerebral arteriovenous differences of oxygen content were performed, permitting an indirect measurement of cerebral blood flow (Qc*), assuming a constant cerebral metabolic rate. Arterial and, in 11 animals, sagittal sinus blood was withdrawn for analysis of PO2, PCO2, oxygen content, and pH at the time of the flow measurements. Preliminary analysis showed the best predictor of Qc and Qc* to be the reciprocal of the arterial oxygen content (1/CaO2). Multiple linear regression analysis combining the effects of 1/CaO2 with arterial PCO2 (PaCO2) gave the following equations: Qc = 458.8 (1/CaO2) + 2.68 PaCO2 - 107.93 (R2 = 0.68); Qc* = 435.54 (1CaO2) + 2.20 PaCO2 - 75.03 (R2 = 0.86). As a result of the hyperbolic relationship between Qc (and Qc*) and CaO2, changes in CaO2 at the low levels found during intrauterine life exert an important influence on the fetal cerebral circulation.

Animals↗

Insulin effect on fetal glucose utilization.

Insulin infused into a sheep fetus over a 3-hr period at the rate of approximately 0.24 U.kg-1.h-1 increased fetal glucose uptake (utilization) from 4.4 +/- 0.7 mg.min-1.kg-1 to 6.9 +/- 0.9 mg.min-1.kg-1 as compared to a noninsulin control period. Insulin administration did not alter fetal oxygen consumption (8.6 +/- 0.7 ml.min-1.kg-1 vs. 7.7 +/- 0.7 ml.min-1.kg-1), umbilical blood flow (220 +/- 1 ml.min-1.kg-1 vs. 209 +/- 16 ml.min-1.kg-1), or the placental clearances of antipyrine (114 +/- 7 ml.min-1.kg-1 vs. 109 +/- 8ml.min-1.kg-1) and urea (24.5 +/- 2.2 ml.min-1.kg-1 vs. 25.0 +/- 2.1 ml.min-1.kg-1). Fetal plasma glucose concentration fell significantly (0.22 +/- 0.01 mg.ml-1 to 0.16 +/- 0.01 mg.ml-1) during insulin infusion. The insulin effect on fetal glucose uptake occurred over a range of maternal glucose concentrations (0.32 leads to 0.78 mg.ml-1), which were not altered by the infusion of insulin in the fetal compartment. Insulin has a specific effect on increasing fetal glucose uptake and utilization.

Animals↗

Comparison of uterotrophic and vascular effects of estradiol-17beta and estriol in the mature organism.

Estradiol-17beta (E2) has been considered the most potent of the natural estrogens in terms of uterine growth and vasodilatation. As a result of studies of uterine growth in rodents, estriol (E3) has been considered an "impeded" estrogen. In this study, direct comparisons of the actions of E2 and E3 on the sheep uterus were made in nonpregnant, oophorectomized ewes by using bilateral uterine artery catheters and electromagnetic flow transducers. Intra-arterial injections of E2 or E3 had equal growth-promoting and vascular effects. There were slight but statistically significant differences in the time course of vasodilatation. Estriol induced a more prolonged dilatation than did estradiol.

Animals↗

Fetal cerebral oxygen consumption at different levels of oxygenation.

Cerebral oxygen consumption (VCO2) was measured in 10 unanesthetized, chronically catheterized fetal sheep at 130-140 days of gestation. The VCO2 was calculated using cerebral blood flow (QC) measured with radioactive microspheres and the cerebral arteriovenous difference of O2 content (C(a-V)O2) calculated from preductal arterial and sagittal sinus venous blood. The ewe was exposed to varying concentrations of oxygen, resulting in fetal arterial oxygen contents (CaO2) of 0.89-5.58 mM, arterial oxygen tension (PaO2) values of 14-36 Torr, and cerebral venous oxygen tension (PVO2) values of 9-25 Torr. Although there was a clear relationship between the fetal CaO2 and C(a-V)O2, this was shown to be the result of changes in Qc rather than changes in VCO2. There was not a statistically significant correlation between either CaO2 or PVO2 and VCO2 over this range of oxygenation. On the other hand, C(a-V)O2 was highly correlated with Qc. There is no evidence that VCO2 is a function of oxygen tension (PO2) in the unanesthetized fetal sheep as long as the sagittal sinus PO2 is greater than or equal to 9 Torr.

Animals↗

The effect of various vasoactive compounds upon the uterine vascular bed.

The effects of various vasodilators on the uterine vascular bed were investigated in nonpregnant, oophorectomized sheep with chronically implanted flow probes and catheters inserted into branches of the uterine arteries. A 1 mug dose of estradiol-17beta (0.224 muM) produces a maximum uterine blood flow response after intra-arterial injection. Adenosine (24 muM) and bradykinin (0.02 muM) were observed to increase blood flow to levels achieved by 1 mug of estradiol-17beta. Acetylcholine, isoproterenol, and histamine were less potent in their vasodilator activity. Atropine, propanolol, and diphenhydramine did not inhibit the increase of uterine blood flow induced by estrogens.

Acetylcholine↗

Effect of estradiol-17beta on blood flow to reproductive and nonreproductive tissues in pregnant ewes.

The effect of estradiol-17beta (1 mug per kilogram) on regional blood flow and cardiac output was studied by means of radionuclide-labeled microspheres in 6 nonpregnant and 13 pregnant ewes five to seven days after operation. Estradiol caused vasodilation in myometrium, endometrium, and placental cotyledons throughout pregnancy, but these responses were significantly less than the fifteenfold increase seen in the nonpregnant uterine tissues. Significant vasodilation also occurred in the ovaries, cervix, vagina, uterine tubes, mammary gland, skin, and adrenal glands of pregnant ewes. Cardiac output increased by 14%. No significant change in uterine oxygen consumption was associated with the increase in blood flow to the pregnant uterus.

Adrenal Glands↗

Effects of epinephrine on distribution of blood flow in the pregnant ewe.

Seven pregnant ewes ranging from 85 to 140 days of gestation were infused with systemic doses of epinephrine and uterine arterial flow dose-response curves were determined. With a constant systemic infusion of epinephrine at a mean rate of 0.29 +/- 0.03 mug/Kg.-min., and the radionuclide lebeled microsphere method to measure arterial blood flow, a 38.5 per cent decrease in total uterine arterial blood flow was demonstrated while systemic pressure was unaltered. At this dose the reduction in endometrial blood flow was significantly greater (-58.7 per cent) than that in either the myometrium (-36.9 per cent) or placental cotyledons (-34.5 per cent) (p less than 0.025 and less than 0.005, respectively). There also occurred a decrease in blood flow to the mammary gland and the pancreas, whereas increased in blood flow to the skeletal muscle, adipose tissue, and spleen were documented. It is evident from this study that during the period of ovine pregnancy investigated, the vascular bed of all tissues comprising the pregnant uterus, including the placental cotyledons, are sensitive to the vasoconstrictive effects of epinephrine.

Animals↗

Umbilical uptake of amino acids in the unstressed fetal lamb.

The whole blood concentrations of 22 amino acids were measured in a chronic, unstressed fetal lamb preparations. Samples were taken daily from the umbilical artery, umbilical vein, and maternal artery over the latter quarter of gestation. 73 sets of samples (from the umbilical artery and vein and the maternal artery) from 13 animals were analyzed for amino acid levels. Oxygen contents were determined simultaneously in 48 sets (umbilical artery and vein) to relate fetal oxygen consumption to amino acid uptake via the umbilical circulation. The results indicate that there is no umbilical uptake of the acidic amino acids, glutamate and aspartate; there is, in fact, a net flux of glutamate out of the fetus into the placenta. As both of these amino acids are major constituents of body proteins, the data indicate that they are formed within the fetus. The umbilical uptake of some neutral and basic amino acids (e.g., valine, leucine, isoleucine, arginine, phenylalanine, and tyrosine) is in considerable excess of estimated growth requirements, suggesting that some amino acids undergo extensive transamination and oxidative degradation in the fetus. Finally, the net uptake of nitrogen, carbon, and calories by the growing ovine fetus in the form of amino acids, glucose, and lactate is compared to estimated requirements as determined in previous studies.

Amino Acids↗

Mammary blood flow and endocrine changes during parturition in the ewe.

The temporal relationship between changes in mammary blood flow (MBF) and changes in the concentration of plasma prolactin, progesterone, estradiol-17beta, and cortisol, was examined in chronic sheep preparations undergoing spontaneous labor (Group I) or labor induced by an infusion of dexamethasone (1 mg/24 h) to the fetus (Group II). In Group I, an increase in prolactin (45 to 489 ng/ml), a decrease in progesterone (15 to 4 ng/ml), and an increase in MBF (97 to 365 ml/min) occurred at about the same time, whereas increases in estradiol-17beta (80 to 211 pg/ml) and cortisol (9 to 39 ng/ml) followed the change in MBF. A similar pattern of changes in MBF and hormonal concentrations occurred over a shorter period when premature labor was induced in the animals in Group II. These findings suggest that changes in plasma prolactin and progesterone concentrations play an important role in the regulation of MBF at the time of parturition.

Animals↗