B.K. van Kreel

Placental transfer and metabolism of purines and nucleosides in the pregnant guinea pig

The placental transfer and metabolism of several purines and nucleosides have been investigated using an artificially perfused guinea-pig placenta. A model describing transfer and metabolism in the uteroplacental unit is constructed and applied. Measurements of oxypurines and guanine have been performed in vivo in the blood of pregnant guinea pigs and their fetuses. It appears that only the oxypurines and, to a lesser extent, guanine are present in the maternal and fetal circulations. These purines could be involved in transfer from mother to fetus and used for salvage in the fetal tissues.

Transport and accumulation of α-aminoisobutyric acid (A.I.B.) in the guinea pig placenta

Active transport of A.I.B. from mother to fetus was studied. This was done in the intact animal and using the isolated placenta, artificially perfused at both sides. It was shown that A.I.B. is actively accumulated in the placental cells. An estimate of the kinetic constants is given. It is shown that this accumulation takes place predominantly from the maternal side of the placenta.A.I.B. that has been accumulated is cleared to the maternal and fetal circulation in equal amounts. So the netto active transport from mother to fetus is brought about by an unequal distribution of carriers, the maternal side being most active.

Transfer and dynamics of uric acid in the pregnant rhesus monkey

The objective of the present study was to develop a mathematical model of the dynamics of uric acid between fetal and maternal compartments in the term pregnant rhesus monkey. In 3 different animals 14C-labeled uric acid was injected into the fetal circulation, the amniotic fluid and the maternal circulation, respectively. In one experiment no uric acid was administered and the fetus was deliberately killed at the beginning of the experiment. Samples of fetal and maternal blood, maternal urine and amniotic fluid were collected at regular intervals. Semilogarithmic time-activity curves were constructed and time constants were determined. An open four-compartment model (fetal-placental plasma, fetal-placental interstitial space, amniotic fluid and maternal plasma) was applied to describe the intercompartmental dynamics of uric acid. Transplacental clearance was approx. 1 ml X min-1 in both directions, maternal renal clearance was about 17 ml X min-1. These results and the calculated values of the other intercompartmental clearances support earlier results, obtained with the steady infusion method. Uric acid concentrations in amniotic fluid and fetal plasma appeared to increase significantly during the experiments. The rise in amniotic fluid levels can only be explained by accepting a yet undefined compartment in which uric acid is produced and cleared directly into the amniotic cavity. It is speculated that this additional compartment could be the fetal lung.Data from the literature suggest that uric acid produced by the fetus could pass across the placenta and contribute to the observed increase in maternal plasma levels of uric acid in preeclamptic pregnancy. To investigate this hypothesis, fetal transplacental and renal uric acid clearances were estimated in 4 term pregnant rhesus monkeys by means of the steady infusion method using 14C-labeled uric acid. Allantoin clearances were determined in one pregnant monkey. Samples of maternal and fetal arterial blood were collected at regular intervals. The total amount of fetal urine produced during the experiment was collected at the end of the experiment. In addition, maternal endogenous renal uric acid and creatinine clearances were measured in 6 term pregnant monkeys. Fetal transplacental uric acid clearances appeared to be almost entirely limited by placental permeability and varied between 3.6 and 8.6 ml X min-1 X kg-1 of fetal weight; fetal renal clearances were between 0.11 and 0.20 ml X min-1 X kg-1. The allantoin clearances were found to be of the same magnitude. Maternal renal clearances of uric acid and creatinine were almost equal (mean 3.2 +/- 0.6 and 3.0 +/- 0.5 ml X min-1 X kg-1 of maternal weight, respectively). Extrapolation of these data to human preeclamptic pregnancy reveals that it is unlikely that fetal uric acid could significantly contribute to the maternal uric acid load.

Transport of Uric Acid and Hypoxanthine Across the Isolated Guinea Pig Placenta

Transport of uric acid and hypoxanthine across the isolated guinea pig placenta is investigated quantitatively. The clearances measured are independent of concentration. It is shown that the uric acid transport is not greatly influenced by variations in flow, so it is concluded that the uric acid transport is membrane limited. The clearance of hypoxanthine is even less than the uric acid clearance, so hypoxanthine transport is also membrane limited. Xanthine oxidase is shown to be present in the uterine tissues, and an apparent Km and a maximum velocity have been determined.

Transfer and dynamics of uric acid in the pregnant rhesus monkey. II. A mathematical model.

Abstract The objective of the present study was to develop a mathematical model of the dynamics of uric acid between fetal and maternal compartments in the term pregnant rhesus monkey. In 3 different animals 14 C-labeled uric acid was injected into the fetal circulation, the amniotic fluid and the maternal circulation, respectively. In one experiment no uric acid was administered and the fetus was deliberately killed at the beginning of the experiment. Samples of fetal and maternal blood, maternal urine and amniotic fluid were collected at regular intervals. Semilogarithmic time-activity curves were constructed and time constants were determined. An open four-compartment model (fetal-placental plasma, fetal-placental interstitial space, amniotic fluid and maternal plasma) was applied to describe the intercompartmental dynamics of uric acid. Transplacental clearance was approx. 1 ml · min −1 in both directions, maternal renal clearance was about 17 ml · min −1 . These results and the calculated values of the other intercompartmental clearances support earlier results, obtained with the steady infusion method. Uric acid concentrations in amniotic fluid and fetal plasma appeared to increase significantly during the experiments. The rise in amniotic fluid levels can only be explained by accepting a yet undefined compartment in which uric acid is produced and cleared directly into the amniotic cavity. It is speculated that this additional compartment could be the fetal lung.

The influence of flow rates and flow distributions on diffusion controlled transport across the isolated guinea pig placenta

SummaryThe influence of flow rates and flow distributions on diffusion controlled transport across the isolated guinea pig placenta was investigated.It was shown that the transport of antipyrine and tritiated water could be explained by simple diffusion and concluded that the maternal and fetal circulations are directed countercurrently. Antipyrine and tritiated water were also used to calculate which part of the maternal and fetal circulations were directed away from the exchange area. One of the models developed by Meschia (1) was changed to account for existing shunts in the maternal and fetal circulations.

Placental and nonplacental drainage of the uterus in the pregnant rhesus monkey

Abstract The proportion of placental to nonplacental drainage of the pregnant uterus of the anesthetized term rhesus monkey was assessed by means of a steady-state transplacental diffusion technique involving infusion of tritiated water at a constant rate into the fetal circulation and determination of the concentrations of radioactivity in the principal veins draining the uterus. No placental blood appeared to be drained through the hypogastric veins. There was considerable variation in the proportion of placental to nonplacental blood in each of the ovarian veins among the 6 animals studied. Ligation of one of the ovarian veins invariably resulted in a decrease in the transplacental clearance of tritiated water. It is concluded that blood samples from the ovarian veins of the pregnant rhesus monkey are generally not representative of the venous drainage of the placentas, which poses an important problem in the application of a diffusion equilibrium technique in this primate for measurement of uterine blood flow and consumption of gases based on the Fick principle.

A NETWORK THERMODYNAMIC MODEL OF THE CONCENTRATING PROPERTIES OF THE RABBIT/RAT KIDNEY IN THE STEADY STATE USING THE ELECTRONIC NETWORK SIMULATION PROGRAM SPICE

A model for the simulation of the diluting and concentrating properties of the rabbit and rat kidney is developed. Translation of the physical model into an electronic one brings the model into a form that can be handled by the electronic network simulation program SPICE. The steady state responses of both kidneys to various inputs are calculated under certain conditions.

Thermodynamic network modelling of transfer across the perfused guinea-pig placenta, using SPICE

Abstract The response of the dually perfused guinea pig placenta to bolus inputs of the marker substances 125 I-albumin and tritiated water is used to model vascular placental topology and membrane characteristics. This is accomplished by generating a thermodynamic network containing ten adjustable variables describing flow and transfer quantitatively. After translation of the network into an electronic circuit the parameter values are determined with the use of the SPICE program. The results are then used to estimate unknown physiological variables like shunted flow, membrane permeabilities, etc. This model has potential usefulness in the study of those areas of placental physiology in which transient analysis is required.