Placental oxygen

Concerning the metabolism of triterpenes and steroids, quite a number of P450 catalyzed transformations are very important, namely the 14a-demethyla-tion of lanosterol [50], the side-chain cleavage of cholesterol [51]and pregnenes [52], and the desaturation of ring A of androgens with concomitant oxidative removal of C(19) [53]. The latter reaction is catalyzed by human placental aromatase, associated with a NADPH-dependent reductase, and requires three moles of oxygen and three moles of NADPH in order to oxidize andro-stenedione 45 to formic acid and estrone 46, Fig. 10. 

Ergot alkaloids contain lysergic acid (see ergotamine formula in A). They act on uterine and vascular muscle. Ergometrine particularly stimulates the uterus. It readily induces a tonic contraction of the myometrium (tetanus uteri). This jeopardizes placental blood flow and fetal oxygen supply. Ergometrine is not used therapeutically. The semisynthetic derivative methylergometrine is used only after delivery for uterine contractions that are too weak. 

A 26-year-old woman with a history of multiple substance abuse required emergency caesarean section at 30 weeks of gestation as a result of crack cocaine-induced placental abruption and fetal distress (251). Her admission blood pressure was 145/95 mmHg, heart rate 95/minute and respiratory rate 20/minute. The fetal heart rate was 130/minute and non-reactive, with late and variable decelerations and no response to maternal oxygen administration. Spinal block with bupivacaine, fentanyl, and morphine was performed with the patient in a sitting position. No maternal or neonatal postoperative complications were reported. 

Ma, T. Yang, S.-T. Kniss, D.A. Oxygen tension influences proliferation and differentiation in a tissue engineered model of placental tropho-blast-like cells. Tissue Eng. 2001, 7, 495-506. 

Thyroid hormones also accelerate fetal lung maturation. Fetal thyroid hormone levels may be increased by antenatal administration of thyrotropin-releasing hormone (TRH), a tripeptide that crosses the placental barrier, stimulates fetal pituitary production of thyroid stimulating hormone (TSH), and which, in turn, increases fetal thyroid hormone production (Chapter 33). This indirect method of enhancement of fetal thyroid hormone production is utilized because thyroid hormones do not readily cross the placental barrier. Insulin delays surfactant synthesis and so fetal hyperinsulinemia in diabetic mothers may increase the incidence of RDS even in the full-term infant. Androgen synthesized in the fetal testis is the probable cause of a slower onset of surfactant production in male fetuses. Prophylactic, or after onset of RDS, administration of synthetic or natural pulmonary surfactants intratracheally to preterm infants improves oxygenation and decreases pulmonary morbidity. 

OH)D-la-hydroxylase is found in the inner mitochondrial membrane of the cells lining the proximal convoluted renal tubules. It is a mixed-function oxidase that requires molecular oxygen, a flavoprotein, a ferredoxin, and a cytochrome P-450 for activity. It is inhibited by carbon monoxide. Placental tissue contains la-hydroxylase activity, as do cultured bone cells and macrophages. This finding is of questionable importance under most circumstances, however, since l,25-(OH)2D is not present in significant amounts in nonpregnant, nephrectomized animals. 

The extrauterine exposure to drug in rodents may differ from that of intrauterine exposure in nonhuman primates because metabolic mechanism could differ in the extrauterine situation especially if the drug is being administered orally, and physiological influences will differ between the intrauterine and extrauterine situation, for example, pulmonary versus placental oxygen supply, nutrient supply, or different kidney function. 

Meperidine crosses the placental barrier and, even in reasonable analgesic doses, causes a significant increase in the percentage of babies who show delayed respiration, decreased respiratory minute volume, or decreased oxygen saturation, or who require resuscitation. Fetal and maternal respiratory depression induced by meperidine can be treated with naloxone. The fraction of drug that is bound to protein is lower in the fetus concentrations of free drug thus may be considerably higher than in the mother. Nevertheless,... 

In the placenta a volume of oxygen sufficient for fetal needs must diffuse across the membranes from maternal to fetal blood during the short time the two circulations are in close contact. This oxygen transfer is a function of several factors which include uterine and umbilical arterial 02 partial pressures, maternal and fetal placental blood flow rates, the 02 capacity and 02 affinity of maternal and fetal hemoglobin, the diffusing capacity of the placenta, the amount of C02 exchanged, and the vascular arrangement of maternal to fetal vessels. 

The CO diffusing capacity, DPco, of sheep was measured at various 02 tensions in a hyperbaric chamber using a method similar to that outlined above (12). DPco varied as a function of the oxygen tension. In Figure 2 the reciprocal of DPco is plotted as a function of the reciprocal of the diffusing capacity of the maternal and fetal red blood cells. From the plot the slope is the reciprocal of the value of V, the maternal and fetal capillary blood volume while the intercept is the reciprocal of Dmco- From these studies we calculated that the resistance of maternal and fetal red blood cells was approximately one-third of the total resistance while the resistance of the placental membrane per se was about two-thirds of the total resistance to 02 diffusion (12). This is in contrast to previous studies which assumed that the placental membrane per se constituted the total resistance to diffusion. 

Hg) at time t on the maternal and fetal sides, Vm and Vf are the maternal and fetal capillary blood volumes (ml) and Dp is the placental diffusing capacity for 02 [ml/(min X mm Hg)]. While these equations ignore placental tissue oxygen consumption, this will be considered later. 

Equations 5 and 6 may be modified to allow for placental oxygen consumption by assuming the rate loss of 02 to the tissues proportional to the partial pressure difference between the capillary blood and the surrounding tissue ... 

In neither case would 02 consumption explain the total uterine to umbilical vein oxygen tension difference. Equilibrium would merely occur at a lower po2- If placental tissue were supplied with 02 solely from fetal blood, the maternal to fetal end-capillary po2 difference would... 

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