Permeability of the human placenta to bicarbonate: in-vitro perfusion studies.

The effect of maternal acidosis on fetal acid-base balance was studied in a dual circuit perfusion of a single cotyledon in normal, term, human placentas. Both the fetal and maternal (intervillous) circulations were perfused with a Krebs-Ringer solution adjusted to pH values between 7.35 and 7.45. After a control period, the perfusate in the maternal circulation was replaced by an acidified medium (mean pH 7.06) for 30 min. This was followed by a second control period of 30 min during which the acidified maternal perfusate was replaced with the original medium. During the 30 min of maternal acidosis, fetal vein pH was not significantly altered despite the large decrease in maternal artery pH, but there was an efflux of total CO2 (tCO2) from the placenta into the maternal circulation which was not matched by an influx of tCO2 from the fetal circulation. The tCO2 transferred was in the form of bicarbonate rather than dissolved CO2, but the maximal rate of tCO2 transfer of in the form of bicarbonate was lower than the rate of placental transfer of tCO2 necessary in vivo. It is probable therefore that bicarbonate does not play a major role in placental CO2 transfer but the placental tissue bicarbonate pool may play an important part in buffering the fetus against changes in maternal pH or blood gas status.

Mid-trimester pregnancy--a time of tranquility or activity?

A number of compounds in pregnancy blood reach a maximum or minimum concentration at around 20-24 weeks of pregnancy, a period of conspicuous clinical tranquility. The compounds mostly derive from either fetal tissue or decidua and it is suggested that they may be part of an elaborate mechanism which controls invasion of the uterine wall by trophoblast.

Mechanical and metabolic viability of a placental perfusion system in vitro under oxygenated and anoxic conditions.

In vitro dual circuit perfusion of the placenta with well-oxygenated medium results in the continuous and stable consumption of oxygen and glucose over a 2-h perfusion period. This is reflected in a stable production of lactate and an energy charge which is higher at the end of the perfusion period than that seen in fresh placental tissue immediately after vaginal delivery. Anoxic perfusion causes an increase in glucose consumption which is more than twofold higher than that seen in the oxygenated perfusion, resulting finally in placental uptake of glucose not only from the maternal but also from the fetal circulation. Lactate production is increased during the anoxic perfusion, while the final tissue energy charge value lies between the values observed for fresh tissue and for the oxygenated perfusion. The shift to anaerobic metabolism shown by placental tissue in anoxic conditions enables continued functioning of the tissue over the 2-h perfusion period but it appears that under anoxic conditions the tissue may incur an energy debt not observed in oxygenated perfusions.

Scalp blood flow measured by the xenon clearance technique and transcutaneous PO2 in the fetal lamb.

Scalp blood flow and transcutaneous (tc) PO2 were measured in four fetal lambs at 130-135 days of gestation. Scalp blood flow was measured by the xenon clearance technique using a technetium source to correct for changes in distance from the detector. The effect of circular pressure, the so-called "tonsure effect" on scalp flow and tcPO2, was evaluated by pressing a ring on the scalp. A circular pressure between 20-30 mmHg markedly reduced local scalp blood flow and was sufficient to reduce tcPO2 to zero. We found evidence of significant recirculation of xenon in the fetal circulation indicating right-left shunting. This study showed that the tonsure effect seriously affected scalp blood flow and tcPO2 in the fetus.

Nucleotide, nucleoside and purine base concentrations in human placentae.

Nucleotides, nucleosides and purine bases in trichloroacetic acid extracts of freeze clamped samples of human placenta have been measured by high-pressure liquid chromatography. The concentrations of the nucleotides concerned with energy transduction, ATP, ADP and AMP, and especially the energy charge, are stable over periods of ischaemia of 30 min. Concentrations of 14 nucleotides, including UDPAG, GDP Man, UDP and CTP, have now been defined. In addition, the concentrations of hypoxanthine, xanthine, uridine, adenine and inosine are indicated. Concentrations of the vasodilator adenosine are similar to the apparent Michaelis constants of its main metabolizing enzymes adenosine kinase and adenosine deaminase. The availability of 'normal' values of adenine nucleotide concentrations in human placenta should permit the detection of 'placental insufficiency' of energy supply, if this condition exists.

Studies of a single placental cotyledon in vitro: II. The intravascular volume.

The intravascular volume of isolated perfused human placental cotyledons was measured by the mean transit time of injected radio-iodine labelled human serum albumin. The technique gives highly reproducible results with no evidence of change with time. The mean intravascular volume was about 6 ml per 100 g of tissue, some 20 ml for an average placenta at term.

Studies of a single placental cotyledon in vitro: III. The dimensions of the villous capillaries.

The capillary beds of ten isolated perfused placental cotyledons were examined by injecting microspheres ranging from 2 microgram to more than 20 microgram diameter into the villous circulation. As many as 25 per cent of capillaries may be less than 4 microgram in diameter; there are virtually none whose diameter exceeds 11 microgram and there is no evidence of large diameter vascular shunts.

Raised hypoxanthine, xanthine and uridine concentrations in meconium stained amniotic fluid and during labour.

Amniotic fluid samples were obtained at induction of labour in 64 women; in 15 of these there was meconium staining of the amniotic fluid; the remainder showed no signs of fetal distress. Using high pressure liquid chromatography, compared to the samples from normal patients there were highly significantly raised levels of hypoxanthine, xanthine and uridine in the meconium stained samples; oxypurines in the meconium itself could not explain the difference. Where serial samples were obtained during labour by intrauterine catheter, a terminal rise in oxypurine levels was apparent. Where the proportion of oxypurine present as hypoxanthine exceeded one per cent in amniotic fluid at the time of induction, there was a significantly greater occurrence of late fetal heart rate decelerations in the ensuing labour. These findings are consistent with other evidence that when tissues become hypoxic the metabolic products of nucleotide breakdown escape from the cells and appear in extracellular fluid. Oxygen lack in the fetus probably causes loss of these compounds from the hypoxic kidneys to the urine so that they appear in amniotic fluid.

The measurement of hypoxanthine, xanthine, inosine and uridine in umbilical cord blood and fetal scalp blood samples as a measure of fetal hypoxia.

Hypoxanthine, xanthine, inosine, urate and uridine, were measured in 149 samples of umbilical cord plasma using high pressure liquid chromatography. In spite of a good correlation with the simpler oxygen consumption method for measuring hypoxanthine, there was no clear discrimination between hypoxic and well oxygenated infants, although mean concentrations were higher in infants with well defined criteria of intrapartum hypoxia or bith asphyxia, there was overlap with the normal range. Fetal scalp blood samples were also found to be clinically unhelpful in the diagnosis of intrapartum hypoxia, at least in part due to variable degrees of haemolysis in the specimens. There were poor correlations between hypoxanthine concentrations and those of hydrogen ion, base deficit and lactate. Uridine concentrations were significantly higher in arterial cord blood than in venous cord blood but hypoxanthine or xanthine concentrations did not show this difference.