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Biomedical subjects

G Meschia

Publications and source records attributed to G Meschia.

At least 91 records · Page 5Linked to original sources

Fetal oxygen uptake, oxygenation, and acid-base balance as a function of uterine blood flow.

The rate of O2 delivery to the pregnant uterus (FaO2) was decreased in chronic sheep preparations by mechanical occlusion of uterine blood flow. The relationship of uterine venous O2 saturation (SVO2) to FaO2 was curvilinear with convexity toward the SVO2 axis. As SVO2 decreased, there was a decrease in uterine and umbilical venous O2 tension (PO2), with no appreciable reduction of the PO2 difference between the two veins and a decrease in the umbilical vein O2 delivery rate. Fetal O2 uptake and base excess remained normal as the umbilical vein O2 delivery rate was reduced from 1.1 to 0.6 mmol . min-1 . kg-1 but decreased markedly at an O2 delivery rate less than 0.5. Umbilical venous CO2 tension (PCO2) was higher than, and strongly correlated with, uterine venous PCO2 (R = 0.954). These observations support a venous equilibration model of ovine placental exchange and demonstrate that under normal physiological conditions the O2 supply to the fetal lamb is approximately twice the value necessary to maintain an adequate fetal O2 uptake and a normal fetal base excess.

Acid-Base Equilibrium↗

Fetal heart rate in relation to body mass.

In contrast to the inverse relation of heart rate to body mass in adult mammals, the heart rate of immature fetuses is unrelated to body mass and approximately constant among different species. With maturation, fetal heart rate decreases in a large mammal but tends to increase in a small mammal. These maturational changes reduce the difference between the heart rate of a term fetus and the heart rate which is "appropriate for body mass" as calculated by means of the allometric equation for adults. The comparative physiology of fetal heart rate supports the hypothesis that immature fetuses of small and large mammals have similar oxygen consumption rates per unit body mass.

Aging↗

Glucose and lactate oxidation rates in the fetal lamb.

Both glucose and lactate are nutrients of the ovine fetus. Each may be used by the fetus as a fuel for oxidation or as a source of carbon for energy storage and net tissue accretion. The present report describes the oxidation rates of glucose and lactate in vivo for the fetal lamb over a relatively short time period. The fraction of fetal glucose or lactate oxidized was defined as the ratio of 14CO2 excretion across the umbilical circulation to the net entry of [14C]glucose or [14C]lactate into fetal tissues. The fraction of glucose oxidized over a 3-hr study averaged 61.2%, accounting for 2.55 mg X min-1 X kg-1 of glucose oxidized and for 28% of the simultaneous net oxygen uptake. The fraction of lactate oxidized averaged 71.5%, accounting for 4.12 mg X min-1 X kg-1 of lactate oxidized. Oxidation fractions and rates for both glucose and lactate increased with their concentrations in fetal blood suggesting sparing of other fuels for oxidation at higher glucose and lactate concentrations.

Animals↗

Placental transfer as a function of uterine blood flow.

The effect of variations of uterine blood flow (F) on placental transfer was examined in six chronic sheep preparations by measuring the placental clearances of ethanol (CE) and antipyrine (CA) at different levels of F. Norepinephrine infusion, hemorrhage, and occlusion of the terminal aorta were used to reduce F below normal. The reduction of F had no appreciable effect on umbilical blood flow (f). In each ewe, CE significantly correlated with F. The CE vs. F relationship at constant f was curvilinear with convexity toward the clearance axis. Regression analysis showed that the equation 1/CE = 1/.911 F + 1/.831 f could account for most of the CE variance (r2 = 0.97). Implicit in this relation is the concept that, given a certain level of placental perfusion, an F/f ratio congruent to 1 is optimal for the exchange of highly diffusible inert molecules between mother and fetus [CE/(F + f) was maximum at F/f = 0.955]. CA was not significantly different from CE at low clearance level but became smaller than CE at clearance values greater than 300 ml/min. This suggests that a high rates of perfusion placental permeability was a factor in limiting CA.

Animals↗

Relationship between placental blood flow and placental and fetal size in guinea pig.

Blood flow measurements were made using radioactive microspheres in 14 unstressed, conscious, pregnant guinea pigs with gestational age ranging between 34 and 67 days. Within each litter placental blood flow (PBF) was positively correlated to fetal weight (FW), even after correcting for placental weight differences. Although the largest littermate was, on the average, only 30% larger than the smallest, its material placental blood flow was 95% greater. The PBF vs. FW relationship could be described by the allometric equation: PBF = Ai FW2.89 where Ai is a litter-specific coefficient. This study demonstrates that the placenta of the largest littermate is "hyperperfused" compared with its smaller siblings.

Animals↗

Simultaneous measurements of lactate turnover rate and umbilical lactate uptake in the fetal lamb.

Lactic acid represents a major exogenous nutrient for the developing fetal lamb in utero. Our study was undertaken (a) to quantitate the net consumption of lactate by the fetus, (b) to quantitate the net lactate production and metabolism by the placenta, and (c) to compare the net fetal lactate consumption with fetal lactate use, measured simultaneously with radioactive tracers. 14 pregnant sheep were prepared with catheters in the maternal femoral artery and uterine vein and in the fetal aorta and umbilical vein. By simultaneous application of the Fick principle to the uterine and umbilical circulations, placental glucose consumption and placental lactate production were rapid, averaging 39.8 +/- 5.1 and 11.8 +/- 0.7 mg.min-1. Net lactate umbilical uptake averaged 1.95 +/- 0.16 mg-1.kg.min-1. During infusion of L-[14C(U)]lactate, fetal lactate turnover was much more rapid, averaging 6.5 +/- 0.8 mg.kg-1.min-1, and lactate utilization within the anatomic fetus was 5.9 +/- 0.7 mg.kg-1.min-1. During infusion of tracer glucose, endogenous fetal lactate production from glucose and nonglucose substrates averaged 3.0 and 1.5 mg.kg-1.min-1, respectively. The present studies have quantitated under well oxygenated, steady-state conditions, the rapid placental metabolism and production of lactate, the net fetal consumption of lactate, and the rapid endogenous fetal lactate production from glucose and nonglucose substrates.

Animals↗

Foetal and placental metabolisms: their interrelationship and impact upon maternal metabolism.

In summary, foetal and placental metabolisms have certain characteristics which appear to bridge species differences. The consumption of carbohydrate and amino acids by the foetal lamb is adequate to meet the energy, C and N requirements of the foetus both for oxidated metabolism and for growth. Techniques to study foetal or maternal metabolism or both under conditions of a biological steady state, comparatively free of stress, are now readily available in several large mammals and are becoming so for small mammals. This should permit comparative physiologic studies in animals differing widely in diet and in body size. Hopefully, such studies will clarify those characteristics of foetal metabolism which are unique to a species and those which are common to all foetuses.

Amino Acids↗

Rates of protein synthesis and turnover in fetal life.

Uniformly labeled [14C]lysine was infused at constant rate into the inferior vena cava of eight ovine fetuses with gestational ages ranging from 110 to 145 days. The infusion lasted 9 to 13 h and produced a steady-state specific activity of free lysine in the fetal plasma. In the steady state, approximately 9% of the infused radioactivity was excreted by the fetus as 14CO2, indicating fetal catabolism of lysine. At the end of the infusion, the fetal carcass was analyzed for its total content of labeled and unlabeled lysine. The rate of protein synthesis was calculated from the carcass-to-plasma lysine specific activity ratio. The fractional rate constant (Ks) for the unidirectional flux of lysine into fetal proteins was inversely related (r = -0.88) to fetal age: Ks = 0.584 - 0.0036 age (days). In each fetus, Ks was 2-4 times greater than the estimated fractional rate of fetal protein accretion (KG). The discrepancy between Ks and KG demonstrates that a large fraction of protein synthesis in the ovine fetus is devoted to protein turnover.

Animals↗

Simultaneous measurements of umbilical uptake, fetal utilization rate, and fetal turnover rate of glucose.

Fetal umbilical glucose uptake was compared with simultaneous measurements of glucose turnover and utilization rates in 12 pregnant sheep, at a mean of 137 days gestational age (range, 118-146 days). Umbilical glucose uptake was calculated by application of the Fick principle. Fetal glucose turnover rate was measured by a primed-constant infusion of [14C]- and [3H]glucose (glucose turnover rate = tracer infusion rate divided by fetal glucose sp act). The calculation of fetal glucose utilization rate required substraction of the loss of tracer to the placenta from the tracer infusion rate, thus defining the net tracer entry into the fetus for direct comparison with the net umbilical glucose uptake. In fed, normoglycemic sheep, these measurements demonstrated statistical equivalence of umbilical glucose uptake rate (4.77 mg.min-1.kg-1 +/- 0.34 SE) and glucose utilization rate ([14C]glucose, 5.58 mg.min-1.kg-1 +/- 0.54 SE; and [3H]glucose, 7.19 mg.min-1.kg-1 +/- 1.24 SE) when tested by two-way analysis of variance (P greater than 0.1). In three fasted, hypoglycemic sheep, the umbilical glucose uptake rate fell to 1.43 mg.min-1.kg-1 +/- 0.56 SE, which was considerably lower than the simultaneous glucose utilization rate ([14C]glucose, 4.78 mg.min-1.kg-1 +/- 0.48 SE; and [3H]glucose, 6.81 mg.min-1.kg-1 +/- 2.19 SE). Thus, in the normoglycemic, late-gestation fetal lamb, there appears to be little glucogenesis, whereas glucogenesis may become significant during fasting-induced fetal hypoglycemia.

Animals↗

Stimulus summation and tachyphylaxis in estrogen response in sheep.

The response of the uterine circulation to estrogen has been extensively studied. Estrogen is the most potent vasodilator of the uterine bed. The magnitude of the vascular response depends on both the dose of estrogen used and the duration of exposure to estrogen. In this study, the relationship between the arterial concentration of estrogen, the duration and pattern of exposure, and the response was studied. This is a complex relationship, but one that is consistent with accepted models of estrogen-target tissue interaction. It was also shown that prolonged, high-concentration exposure results in tachyphylaxis.

Animals↗

Induction of fetal breathing by metabolic acidemia and its effect on blood flow to the respiratory muscles.

Sustained and vigorous fetal breathing activity was produced in a chronic fetal lamb preparation by infusion into the fetus of either NH4Cl or HCl. Over a 2 to 3 hour period, 20 to 25 mEq/kg were infused. All of the fetuses tolerated blood pH values of 6.7 to 6.8 and survived. The breathing activity began after the completion of the infusion, and consisted of regular 30 to 50 torr inspirations at a rate of 60 to 120 breaths/min. This activity was continuous for as much as 8 hours, and persisted with pauses and decreased amplitude for 24 to 36 hours. During fetal breathing, blood flow to the diaphragm and intercostal muscles increased approximately 12- and sixfold, respectively.

Ammonium Chloride↗

Transplacental diffusion of ethanol under steady state conditions.

The placental clearances of ethanol and antipyrine, uterine and umbilical blood flows (ml/min) were measured in six chronic sheep preparations. The two substances were infused simultaneously at constant rate into the fetal inferior vena cava. In the steady state, blood samples were obtained from the fetal abdominal aorta, common umbilical vein, maternal uterine vein and maternal femoral artery and analysed for the blood concentrations of ethanol and antipyrine. The clearance of ethanol (CE) was related to uterine (F) and umbilical (f) blood flows according to the regression equation: CE = -26 + 0.88 (F x f)/(F + f), (r = 0.987). The ethanol/antipyrine clearance ratio ranged between 1.21 and 0.97 (mean 1.07, 95% confidence limits 1.01-1.14) These data support the hypothesis that the placental clearance of ethanol is primarily flow-limited.

Animals↗

Utilization of substrates by the ovine placenta in vivo.

The uptakes of oxygen, glucose, and amino acids by the pregnant uterus via the uterine circulation and by the fetus via the umbilical circulation have been measured in sheep during the last month of gestation. The umbilical uptakes of oxygen and glucose are approximately 55 and 28%, respectively, of the total uterine uptake. This discrepancy between uterine and umbilical uptakes is due primarily to a large utilization rate of oxygen and glucose by the placenta. Part of the placental utilization of glucose can be accounted for by placental lactate excretion into both maternal and fetal blood. In marked contrast to the pattern of glucose utilization, the comparison of uterine and umbilical amino acid uptakes shows that the bulk of the amino acids taken up by the pregnant uterus is transferred to the fetus. The placenta utilizes glutamate of fetal origin and produces ammonia, which is excreted primarily into the maternal circulation.

Amino Acids↗

Redistribution of cardiac output and oxygen delivery in the hypoxemic fetal lamb.

In hypoxia, fetal cardiac output and the product arterial O2 content x blood flow to the fetal heart and central nervous system (CNS) tend to remain constant. As a consequence the percentage of cardiac output directed to the heart and CNS increases hyperbolically in inverse relation to the oxygen content of the fetal ascending aorta, [O2]as. The fetal lamb maintains [O2]as approximately 0.45 mM (0.45 +/- 0.02 SEM) higher than the O2 content in the abdominal aorta, [O2]ab, over a wide range of oxygenation. When [O2]as decreases below the 2 mM level, the [O2]as--[O2]ab difference (delta O2) decreases also. A mathematical model of the fetal circulation shows that delta O2 is a function of the ratio oxygen consumption of fetal upper body/abdominal aorta blood flow (VU/FA). The behavior of delta O2 in hypoxia can be explained by assuming that the VU/FA ratio is maintained in moderate hypoxia and decreases in sever hypoxia.

Animals↗

Blood flow to fetal organs as a function of arterial oxygen content.

In a sheep preparation the blood flow to fetal organs was studied 3 to 10 days after surgery by means of the microsphere technique over a range of fetal arterial O2 content from 6 to 1 mM. Blood flows to neural tissues (cerebrum, cerebellum, brain stem), heart, and the adrenals increased in inverse relation to arterial O2 content. As a result the arterial supply of O2 to these organs tended to remain constant over the O2 range studied. Blood flow to the fetal lungs decreased progressively with hypoxia. The blood flow to kidneys, digestive tract, pancreas, and carcass had a tendency to remain constant or increase gradually in the transition from high to moderately low levels of arterial O2 content and then to decrease abruptly in more severe hypoxia. Umbilical blood flow did not change systematically in relation to arterial O2 content.

Acid-Base Equilibrium↗