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Biomedical subjects

J J Faber

Publications and source records attributed to J J Faber.

At least 55 records · Page 3Linked to original sources

Distribution of ionic sulfate, lithium, and bromide across the sheep placenta.

Salts of sulfate, lithium, and bromine were injected or infused intravenously into ewes in the last trimester of gestation. Ewes and fetuses had indwelling catheters; most fetuses were nephrectomized. Concentrations were measured in paired maternal and fetal samples over periods of 4--14 days. Maternal excretion of sulfate was too rapid to permit near equilibration of fetal and maternal plasma concentrations; the results, however, did not support the existence of a large potential difference across the exchange barrier. The concentrations of Li+ (given by continuous infusion) and 82Br- in maternal plasma did not change rapidly. The concentrations of these tracers in fetal plasma rose until they were nearly equal to the maternal plasma concentrations. Steady-state transplacental potentials, calculated by use of the Nernst equation, were 5.2 +/- 2.0 (SEM) mV (n = 26) for Li+ and -2.2 +/- 0.8 (SEM) mV (n = 10) for Br-. Nernst potentials calculated from previously measured maternal and fetal plasma concentrations of Na+, K+, Mg2+, and Cl- were +0.4, +3.6, +0.5, and -1.4 mV. We concluded that, of the total potential difference of about -50 mV (fetus negative) between the fetal lamb and the ewe, only a few mV are dropped across the placental exchange barrier.

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Diffusion permeability and ultrafiltration-reflection-coefficients of Narand Cl- in the near-term placenta of the sheep.

Experiments were performed on unanaesthetized ewes in the last third of pregnancy. Fetuses and ewes had indwelling vascular catheters. In some of the experiments fetal urine was drained to the exterior by means of an indwelling vesicular catheter. Placental diffusion permeabilities were measured with 22Na+ and 36Cl- injected into eight fetuses. Volumes of distribution of Na+ and Cl- in the conceptus were Na+: 548 +/- 24, Cl-: 760 +/- 51 (ml/kg fetal wt +/- SEM). Diffusion permeabilities were Na+: 5.2 X 10(-3) +/- 0.3 X 10(-3), Cl-: 9.8 X 10(-3) +/- 0.9 X 10(-3) (ml.s-1.kg-1 +/- SEM). Ultrafiltration-reflection-coefficients of Na+ and Cl- in the placental exchange barrier were measured 17 times in seven fetuses with vesicular catheters. The transplacental e.m.f. was estimated from these results, on the assumption that the individual reflection-coefficients of Na+ should correlate with those of Cl-. The best estimate was -1.0 mV (fetus negative), and the best estimates of the placental reflection-coefficients were Na+: 0.83 and Cl-: 0.79. There was a reliable negative correlation (P < 0.01) between the calculated reflection-coefficients and the osmolality of the urine secreted by the fetus. This suggested that the concentration of vasopressin in fetal plasma affects the membrane characteristics of the placenta. The mean total osmotic force across the placental barrier of the sheep in these experiments was calculated to be 260 Pa (2 mmHg).

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The transplacental potential difference as distinguished from the maternal-fetal potential difference of the guinea-pig.

1. We measured the differences in electrical potential between mother and fetus in the guinea-pig. The fetus was 33 +/- 2 (S.E. of mean) mV negative with respect to the mother. 2. Salts of bromine, sulphate, rubidium, and lithium were injected into pregnant sows and blood samples were obtained from the sows and their fetuses at various times after injection. The transplacental electrical potentials at which each of these ions would be in electrochemical equilibrium across the placental exchange barrier were calculated from the Nernst equation and the concentrations in maternal and fetal plasmas. 3. The differences in transplacental electrical potential calculated from the steady-state concentrations of these ions in maternal and fetal plasmas were within 1 mV of zero. 4. These observations are consistent with a very small difference in electrical potential across the placental exchange barrier itself, and the generation of a potential difference between mother and fetus at a site other than the exchange barrier.

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Transplacental gradients in the guinea pig.

We measured plasma concentrations of Na+, K+, Mg2+, Cl-, Ca2+, HCO3-, phosphate, lactate, glucose, total amino acids, and total protein, and also the total (freezing point depression) osmolality and the colloid osmotic pressures. Conversion of chemically measured concentrations to osmolalities showed that unrecognized solute (s) were present in maternal (7 mM) and fetal (12 mM) plasma. Statistically reliable transplacental gradients existed only for calcium ion, phosphate, and amino acids, Ionic Na, K Mg, Cl, Ca, HCO3 and lactate were in electrochemical equilibrium at potential differences of -4.2 to +1.3 mV. Total plasma osmolalities were not significantly different in maternal and fetal plasmas in preparations in good condition, but fetal plasma osmolalities rose due to lactate secretion in asphyxiated fetuses. Colloid osmotic pressures were about 5 cmH2O higher in maternal plasmas before 45 days gestation and about 6 cmH2O higher in fetal plasmas after 60 days gestation. In the guinea pig, colloid osmotic pressures are at least as important as intravascular pressures in the regulation of transplacental water flow.

Amino Acids↗

Transfer of hydrophilic molecules by placenta and yolk sac of the guinea pig.

Prenatal transfer of hydrophilic materials was studied in chronic guinea pig preparations of ca. 30-65 days gestation. In most preparations the vitelline (yolk sac placenta) circulation of one of the fetuses was ligated between 1 and 20 days before the experiment. Fetal and maternal serum protein concentrations were recorded as a function of the number of days after ligation. Prenatal transfer of hydrophilic materials of 60-5,500 daltons molecular wt was consistent with diffusion, with some evidence of steric restriction of the larger molecules. There was no difference between operated and sham-operated or control fetuses. However, the transfer of radiolabeled homologous gamma globulin ceased after ligation of the yolk sac vessels. The transfer in control fetuses accounted for most of the prenatal requirements of this protein, as calculated from the increases in fetal weight and serum gamma globulin concentrations as a function of gestational age. There was evidence of a nonspecific suppression of yolk sac function by surgery but no evidence of fetal catabolism of gamma globulin.

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Osmotic flow through the placental barrier of chronically prepared sheep.

An electromagnetic flow sensor was placed on the distal aorta of sheep fetuses in utero, and catheters were placed in a femoral artery and the common umbilical vein. Catheters were also placed in a carotid artery and a uterine vein of the pregnant ewe. Three days postoperatively maternal plasma was hyperosmotic with respect to fetal plasma by all methods: +5.8 +/- 1.4 SE by vapor-pressure osmometry, +2.2 +/- 0.7 SE by freezing-point depression osmometry corrected for bicarbonate loss; and +3.26 mosmol/liter by chemical measurement of plasma constituents. Maternal or fetal plasma was made hypertonic in vivo by infusion of concentrated solutions of mannitol, sucrose, or NaCl. Transplacental water flux was calculated from placental blood flows and arteriovenous differences in water content of the blood. The apparent osmotic conductivity of the placenta was 61 ml2-mosmol-1-kg-1, but this value should be divided by an unknown reflection coefficient to yield the true osmotic conductivity. Separate measurements were made of the placental diffusional permeability of Na+ and Cl- in five chronically prepared sheep fetuses: PSNa+ =0.20 +/- 0.04, PSCl- = 0.27 +/- 0.04 ml/(min-kg fetus). There was a highly significant positive regression between (total) placental permeability and fetal weight.

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Water and electrolyte acquisition across the placenta of the sheep.

Fetal plasma is known to be hyperosmotic with respect to maternal plasma. Although some solutes are actively transported across the placenta and occur in higher concentrations in fetal than in maternal plasma, the total concentration difference is reversed by an opposite difference in the concentrations of electrolytes. Calculations on the basis of the Kedem and Katchalsky equations for a homogeneous membrane demonstrate that active solute transfer and a physiologically plausible hydrostatic pressure difference account for the known rates at which water and electrolytes are accumulated in the fetus. Best estimates of the membrane parameters (per kilogram fetal weight) are PSNa, Cl = 0.23 ml-min-1-kg-1, LpS = 5-10(-6) cm5-min-1-kg-1-dyne-1, and sigma NaCl approximately equal to 0.5. (where PS is the permeability-surface area product, LpS is the filtration coefficient, or sigma is the Staverman reflection coefficient). The driving forces for water and electrolyte transfer (active transfer and hydrostatic pressure) are not used as regulators. Rather, electrolyte permeability, which is the major constraint on fetal growth, and which continuously increases during gestation, makes possible the exponential increase in fetal weight during gestation.

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Steady-state methods for the study of placental exchange.

Published and new data on steady-state exchange of tracers and oxygen are characterized by marked species differences. When the placenta is treated as an ideal diffusion cell of unknown vessel geometry and permeability, the exchange characteristics of oxygen can be used to prove that the exchange of tracers such as acetylene, nitrous oxide, tritiated water and antipyrine is entirely flow limited. The recorded patterns of transfer of flow-limited tracers reveal that some placentas are as effective as counter-current exchangers whereas others mimic the behavior of the less effective types of exchangers. These species differences in apparent geometry are unrelated to the histologic nature of the barrier. The patterns of flow-limited transfer are so similar to those of oxygen transfer that the diffusion resistance to oxygen must be small. The exchange of diffusion-limited (hydrophilic) tracers mimics exchange across capillary membranes in some species and exchange across cell membranes in others. These species differences in diffusion-limited transfer are clearly related to the histologic nature of the barrier and are independent of vessel geometry.

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Fetal homeostasis in relation to placental water exchange.

Fetal growth in utero demands a continuous flow of water and solutes across the placental barrier. We investigated the membrane parameters that control the influx of solutes that are not actively transported and the influx of water. The osmotic conductivity, and the Na+ and Cl- permeabilities of the membrane were measured in chronically instrumented fetal sheep. Transplacental salt flow and water flow were augmented by drainage of fetal urine to the exterior over extended periods of time. Calculation showed that the membrane parameters are: deltaNaCl = 0.83, P.SNaCl = 8.0 10-3 ml.sec-1 kg-1, and LPS = 4.7 10-8 cm5.dyne-1.sec-1.kg-1 (placental surface area S being expressed per kg fetal weight). The chronic infusion of vasopressin into the fetuses at 8 to 11 units per day per kg fetal weight reduced the reflection coefficient deltaNaCl to a mean of 0.63 (P less than 0.03). We concluded that the characteristics of the influx of NaCl and water are compatible with those of a diffusion filtration process, that fetal growth is constrained by the diffusional permeability of the placenta for inert electrolyte and that in the long run fetal growth can only accelerate because placental electrolyte permeability increases. Vasopressin appears to reduce the salt reflection coefficient of the placenta thus enabling the fetus to exert some short term control over its acquisition of water and electrolyte.

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Absence of fetal placental waterfall phenomenon in chronically prepared fetal lambs.

An electromagnetic flow sensor was placed on the distal fetal aorta (umbilical flow fraction 78.1 +/- 1.6 SEM, %), an inflatable occluder was tied around the umbilical cord, and catheters were placed in distal branches of an umbilical artery and vein, a uterine vein, and in the amniotic cavity. An inflatalbe occluder was tied around the vagina of some of the ewes. Control values 3 days after surgery were (mean +/- SE): fetal femoral artery pH, 7.37 +/- 0.01; umbilical blood flow, 186 +/- 14 ml-min-1 .kg fetus-1; fetal arterial blood pressure, 39 +/- 3 mmHg; and umbilical venous pressure, 7.4 +/- 1.0 mmHg (above intrauterine pressure). Fetal weight at autopsy was 3.1 +/- 0.3 kg, n = 11. Small increases in umbilical vein pressure caused immediate decreases in placental blood flow without decreases in fetal arterial blood pressure. The relation between venous pressure and umbilical blood flow at constant arterial pressure was that of an inert system, i.e., no evidence of a surrounding pressure (Starling resistor effect or waterfall phenomenon) could be found with increases in venous pressures of 2-40 mmHg. The results were not affected by increases in uterine vein pressure between 2 and 30 mmHg, nor by anesthesia and supine position of the ewe, nor by ganglionic blockade of the fetal ANS. It was concluded that surrounding pressures in the fetal placental circulation could not be demonstrated.

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The steady state concentration gradients of an electron-dense marker (ferritin in the three-layered hemochorial placenta of the rabbit.

Ferritin was injected into the fetal or the maternal circulation of 27-29-day-pregnant rabbits. After the occurrence of a quasi-steady state, the placentas were prepared for electron microscopy. Ferritin particles were counted in the electron micrographs in the fetal capillaries, in the maternal blood spaces, and in the two interstitial compartments of the three-layered placenta. Under the circumstances of the experiments (excessively elevated plasma ferritin concentrations), no evidence was found for nondiffusional transport of radiolabeled ferritin. Comparison of the standing concentration gradients in the placentas, recorded after maternal and after fetal injection, showed that the interstitial spaces "excluded" ferritin; the plasma-interstitial space ferritin partition coefficients were 10 in the basement membrane space and 3 in the space between the cyto- and syncytiotrophoblasts. 55% of the total concentration gradient across the rabbit placenta occurred across the fetal endothelium, about 45% across the cytotrophoblast, and less than 5% across the syncytiotrophoblast. These figures are believed to reflect the relative contributions of these three layers to the total diffusional resistance in the rabbit placenta. When compared to previous data on the relative contributions of these three layers for small ions and molecules, the present data lead to the conclusion that discrimination of molecular size is a function of the fetal capillary endothelium alone.

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Foetal placental blood flow in the lamb.

1. Fifteen sheep foetuses of 1.5-5.2 kg body weight were prepared with indwelling arterial and venous catheters for experimentation one to six days later.2. Unanaesthetized foetuses were found to have mean arterial and central venous blood pressures of 40 +/- 1.5 (S.E. of mean) and 2.0 +/- 0.3 (S.E. of mean) mm Hg respectively, compared to intra-uterine pressure. Intra-uterine pressure was 16 +/- 0.8 (S.E. of mean) mm Hg with respect to atmospheric pressure at mid-uterine level.3. Mean placental blood flow of the foetuses was 199 +/- 20 (S.E. of mean) ml./(min.kg body wt.). Mean cardiac output in eleven of the foetuses was 658 +/- 102 (S.E. of mean) ml./(min.kg).4. Mean foetal and maternal colloid osmotic pressures were 17.5 +/- 0.7 (S.E. of mean) and 20.5 +/- 0.6 (S.E. of mean) mm Hg respectively at 38 degrees C.5. Intravenous infusions into six ewes of 1.8 mole of mannitol and 0.4 mole of NaCl resulted in significant increases in foetal plasma osmolarity, sodium, potassium, and haemoglobin concentrations, without detectable transfer of mannitol to the foetal circulation.6. In the sheep placenta there is osmotic and hydrostatic equilibration of water. As a consequence, there should be an interaction between foetal placental blood flow and foetal water exchange with the maternal circulation. It was concluded that this interaction tends to stabilize foetal placental blood flow.

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