Lactate carriers in the artificially perfused human term placenta.

Thirty-two isolated cotyledons from human term placentae were perfused artificially with a tissue culture medium on the maternal and the fetal side. The transfer and uptake of labelled L-lactate and D-lactate (test substance) relative to L-glucose (reference substance, extracellular marker) were investigated in steady-state experiments (n = 9) and in a single passage paired tracer dilution technique (n = 23). The L-lactate transfer exceeded the L-glucose transfer two to three times. The L-lactate uptake into the trophoblast--both from the maternal and the fetal side--was more than three times that of D-lactate. L-lactate transfer and uptake were inhibited by phloretin. The L-lactate transfer showed a saturation kinetic at increasing chemical concentrations of lactate. It is concluded that lactate carriers exist both in the maternal and fetal side of the trophoblast.

L-alanine carriers at maternal and fetal surfaces of the guinea pig placenta trophoblast.

An active transport for amino acids exists in maternofetal direction through the hemochorial placenta of man and guinea pig. With respect to the trophoblastic barrier some properties of the transplacental transport at both sides of this tissue are investigated. The results are compared to the methods of the transport of amino acids at intestine and kidney. The maternal and the fetal (basic) membrane can be investigated separately and one after another at one placenta by the technique of the bolus injections. The results were as follows: The 3H-L-alanine uptake is significantly higher by maternal injection than by fetal injection. Opposite to this the backflux is higher out of the trophoblast into the perfusion medium of the donor side at fetal injections. Out of this transplacental transport is higher in materno-fetal direction than in the opposite direction (p less than or equal to 0.05). A sodium dependence of the 3H-L-alanine transport is found at the maternal and fetal side. Nevertheless, the withdrawal of sodium ions inhibits more strongly at the maternal than at the fetal side. The sodium-dependent transport system predominates at the maternal membrane of the trophoblasts. Phloretin only inhibits significantly the uptake (maximal) and the transport of 3H-L-alanine at the fetal side (at the basic membrane). That means that the sodium independent by phloretin inhibited transport system exists mostly, if not totally, at the fetal membrane. Ouabain reduces uptake (maximal and total) and transport of 3H-L-alanine only significantly at the maternal side (p less than or equal to 0.05). Therefore the active sodium transport must be mostly localized at the maternal membrane. The flux of L-alanine diminishes with increasing L-alanine concentrations at the fetal and maternal side. The determinations of the transport capacity (Jmax) and the transport affinity (Km) show that Jmax is significantly higher at the maternal side and Km at the fetal side (p less than or equal to 0.05). By means of these results a model can be described to characterise the transport of amino acid through the placenta.

Atrial natriuretic peptide and cyclic guanosine-3',5'-monophosphate in normal and pathological pregnancies.

The concentrations of atrial natriuretic peptide (ANP) and its presumed second messenger, cyclic guanosine-3',5'-monophosphate (cGMP) were determined in maternal plasma and amniotic fluid. Samples were obtained from normal and pathological pregnancies revealing hydramnios or severe Rh incompatibility between week 16 of gestation and delivery. For analysis of ANP and cGMP, radioimmunoassays were used. ANP and cGMP concentrations in maternal plasma did not differ in normal and pathological pregnancies. In amniotic fluid, we found ANP levels of about 120 pg/ml at 16 weeks of gestation which then decreased below the detection limit of 15.6 pg/ml. In contrast, cGMP levels were low at the beginning of pregnancy (4 pmol/ml) and rose significantly (14 pmol/ml), at the end of pregnancy. Pregnancies revealing severe Rh incompatibility exhibited the same levels as normal pregnancies when regular prenatal transfusions resulted in sufficient blood volume substitution. ANP, a volume-homeostasis-regulating hormone, is already produced in early pregnancy. The meaning of the presumed second messenger, cGMP, requires further investigation.

The metabolism of the isolated artificially perfused guinea pig placenta. I. Excretion of hydrogen ions, ammonia, carbon dioxide and lactate, and the consumption of oxygen and glucose.

In the isolated, perfused guinea pig placenta glucose seems to be a major nutrient of energy metabolism, because the excreted amounts of carbon dioxide and lactate can be explained solely by the catabolism of glucose. In steady state experiments hydrogen ions, ammonia, lactate and carbon dioxide are excreted for at least 90 minutes in rather constant amounts. The production of lactate shows no significant dependence on the glucose concentration in the perfusion fluid. The guinea pig placenta seems to cover its energy requirement mainly by means of anaerobic glycolysis. Of the utilized glucose 76% are metabolized anaerobically. The placenta produces significant quantities of lactate, although it is well oxygenated. A reduction of the oxygen tension in the perfusion fluid does not result in an increase of the production of lactate. Of the hydrogen ions excreted nearly 50% are excreted as ammonia. Although the excreted amounts are small compared with the known transfer rates, they have to be taken into consideration, when studying transplacental transfers of these metabolites.

The metabolism of the isolated artificially perfused guinea pig placenta. II. Difference of excretion of hydrogen ions, ammonia, carbon dioxide and lactate into maternal and fetal veins.

The isolated and artificially perfused guinea pig placenta produces hydrogen ions, ammonia, lactate and carbon dioxide, which are secreted in significant larger amounts into the maternal than into the fetal circulation. The excretion rates of hydrogen ions, lactate and carbon dioxide increase significantly on both sides when the perfusion flow rates are enhanced. If the maternal perfusion flow is reversed the amount of substances excreted at the maternal side is not different from the amount excreted at the fetal side. A reversal of the fetal perfusion flow does no influence the different excretion rates on the maternal and on the fetal side. This unequal distribution between maternal and fetal side can be explained by the anatomical structure of the placenta. In the interlobium, which has been described as area of metabolism, fetal capillaries are rare. Therefore the metabolites of the placenta itself arrive chiefly at the maternal circulation.

[Tocolysis with beta sympathomimetics alone or combined with the calcium antagonist verapamil? I. Effect of verapamil on maternal cardiovascular parameters and the course of pregnancy]. / Tokolyse mit beta-Sympathikomimetika allein oder in Kombination mit dem dem Kalziumantagonisten Verapamil?

In a retrospective study covering 471 cases the influence of the calcium antagonist Verapamil on tocolytic therapy with beta-mimetics was examined. 308 patients received Fenoterol therapy (group A) and 163 were treated with a combination of Fenoterol and Verapamil in a dosage-relation 1/20 (group B). There was no significant difference between group A and B in respect of age, parity, week of gestational age at the beginning of therapy and at delivery, and mode of delivery. The cardiovascular parameters demonstrated alterations as described in literature. The heart frequencies increased significantly in all patients while the systolic and the diastolic blood pressures decreased significantly in hypertonic patients only. These alterations of the cardiovascular parameters were the same in both groups. The efficiency of the tocolytic therapy was tested by comparing the prolongation index (Richter) and the frequency of uterine contractions measured by external cardiotocography. There was no significant difference between groups A and B. Severe complications occurred in 6 patients so that the therapy had to be discontinued (3 women suffered from pulmonary oedemas). These complications were also seen under additional Verapamil application during tocolytic treatment. The side effects as far as reported by the patients were restricted to a significantly lower rate of obstipation in the Fenoterol/Verapamil treated group B. We conclude that administration of the calcium antagonist Verapamil is of no additional value in tocolytic treatment with beta-mimetics.

[Tocolysis with beta sympathomimetics alone or combined with the calcium antagonist verapamil? Influence of verapamil on the fetus]. / Tokolyse mit beta-Sympathikomimetika allein oder in Kombination mit dem Kalzium-antagonisten Verapamil? 2. Einfluss des Verapamil auf den Feten.

In a retrospective study, patients who underwent tocolytic therapy by beta-mimetics were investigated. 308 received Fenoterol monotherapy (group A) and 163 a combination of Fenoterol with the calcium-antagonist Verapamil in a dosage-relation of 1/20 (group B). The review of 287 cardiotocograms showed a significant increase in the foetal heart rate in both groups by about 13% after 114 minutes (A) and 146 minutes (B). Although the diaplacental transfer of Fenoterol to the foetus is very small, a high percentage of foetuses showed an increase in heart rate (84.7% in A, 86% in B). There was a significantly longer duration of foetal tachycardia in group B. Both groups were not different in respect of perinatal mortality (5.4% in A, 5.2% in B), birth weight, APGAR score, and the reasons for paediatric care. The great difference in placental permeability for Fenoterol and Verapamil may cause a danger for the foetus. Since no reasonable improvements are seen, additional Verapamil therapy is not recommended.

Perinatal outcome in fetuses with loss of end-diastolic blood flow velocities in the descending aorta and/or umbilical arteries.

Continuous- and pulsed-wave Doppler velocimetry was used as an additional method of antenatal surveillance in high-risk pregnancy care. During a 30-month period with 4,169 deliveries 226 patients (5.4%) with complicated pregnancies (intrauterine growth retardation, diabetes, hypertension) were investigated. The results had only marginal influence on obstetrical management. In 38 fetuses absence of end-diastolic blood flow velocities (AEDF) was detected in the descending fetal aorta and/or umbilical arteries. Mean birth weight of these fetuses was 1,441 +/- (SD) 690 g at a mean gestational age of 31.8 +/- 6.8 weeks at birth. Twenty fetuses (53%) were growth-retarded (less than 3rd centile). Six fetuses died in utero and 7 during the perinatal period (34% mortality). There was a significant deterioration of perinatal outcome with AEDF in the umbilical arteries at the last antenatal Doppler scan. With AEDF in the descending fetal aorta the Doppler parameter Vmean and with AEDF in the umbilical arteries the pulsatility index yielded additional prognostic information. Doppler velocimetry of the fetal and umbilical vascular system could be of additional value for antenatal surveillance in high-risk pregnancies.

[Prenatal diagnosis of malignant intracranial teratoma in the fetus]. / Pränatale Diagnostik eines fetalen malignen intrakraniellen Teratoms.

At 24 weeks of gestation, an intracranial cystic lesion of 3 cm diameter, without further associated foetal malformations, was detected by ultrasound in a 25-year old nullipara prima gravida, during routine prenatal care. Within 5 weeks, the cystic mass developed into a predominantly solid tumour located at the 3rd ventricle, showing patterns of a rapidly growing malignant intracerebral process. At 29 weeks of gestation, pregnancy was terminated by sectio parva because of a progressive hydrocephalus with a biparietal diameter of 10.2 cm. Autopsy confirmed a malignant teratoma. Foetal intracranial teratomas are rare. Diagnosis and therapy should be carried out in perinatal centres.

Pulsed wave Doppler velocimetry in the descending aorta of chronically instrumented fetal sheep.

Pulsed wave Doppler sonography was used to determine peak systolic velocity (Vpeak), mean maximum velocity (Vmean) and Pulsatility Index (PI) in the descending aorta of chronically instrumented, unanesthetized fetal sheep (days 120-130 of pregnancy). Measurements were done 1-4 days after surgery using a duplex mechanical sector scanner (4.5 MHz) and offset attached pulsed wave Doppler probe (2.25 MHz) during periods of control, intrauterine cooling and rewarming. Mean values derived from the envelope curve of maximum shift frequencies were (controls): thoracic: Vmean 60.9 +/- 9.1 cm/sec, Vpeak 118.9 +/- 17.8 cm/sec, PI 1.57 +/- 0.24; abdominal: Vmean 49.6 +/- 10.9 cm/sec, Vpeak 98.9 +/- 20.4 cm/sec, PI 1.59 +/- 0.41. Vpeak was positively correlated to arterial pressure (r = 0.23) and PI showed an inverse correlation to heart rate (r = -0.22). During cold stress (reduction of fetal core temperature by 2.7 degrees C) and consecutive rewarming Vpeak and Vmean were positively correlated to fetal core temperature and arterial pressure (r = 0.2-0.26). PI revealed a weak negative dependency from core temperature and heart rate (r = -0.19 and -0.18 respectively).

[Normal values for relative Doppler indices. A/B ratio, resistance index and pulsatility index of the uterine artery and umbilical artery in normal pregnancy. A longitudinal study]. / Normalbereiche für die relativen Doppler-Indizes. A/B-Ratio, Resistance-Index und Pulsatilitäts-Index der Arteria uterina und Arteria umbilicalis bei ungestörter Schwangerschaft. Eine Längsschnittstudie.

37 women (of a total of 50) with an uneventful obstetric history, normal course of a singleton pregnancy and spontaneous delivery at term (> 37 weeks, birthweight > 10th centile) were studied at two to four weeks intervals in a longitudinal design using cw-Doppler velocimetry (Doptek 9013,4MHz, SPTA 30 mWcm2, high pass filter 200 Hz, Chichester, U.K.) to establish normal reference values for Doppler flow velocity waveform indices (DI) A/B ratio, RI, PI obtained from uterine and umbilical arteries from 16 to 40 weeks of gestation. Readings from the placental (p) and non-placental (np) uterine and umbilical arteries formed the database from which percentiles (5th, 50th, 95th) were calculated for weeks 16, 20, 24, 28, 32, 36 and 40 of gestation. DI consistently decreased from week 16 to term. For the uterine arteries this decrease was significant from weeks 16 to 24 with a further but insignificant decrease from 24 weeks to term. Up to 24 weeks DI values obtained from the placental side were significantly lower than those from the non-placental side. DI values from the umbilical arteries decreased continuously from 16 weeks to term with a significantly negative correlation DI values to gestational age.