Uteroplacental Unit Research Articles

The lack of an effect of furosemide on uterine prostaglandin metabolism [formula omitted

We determined the effect of 2 mg/kg intravenous furosemide on the production and metabolism of prostaglandin E 2 in the utero-placental unit of pregnant dogs. Uterine venous prostaglandins E 2 and 15-keto-13,14-dihydro E 2 were measured by gas chromatography-mass spectrometry. Even though the dose of furosemide was adequate to effect a good diuresis, neither the production nor the metabolism of prostaglandin E 2 by the uterus was altered by that dose of the drug. Using radioactive microspheres to measure hemodynamic parameters, we observed no change in uterine vascular resistance while renal vascular resistance decreased. Although the renal concentration of furosemide may be higher than the uteroplacental concentration, there is so far no evidence in vivo that usual doses of furosemide enhance the production or inhibit the metabolism of prostaglandin E 2.

Ammonia Production by the Pregnant Uterus

SummaryThe arterial-venous differences of ammonia and oxygen were measured across the uterine and umbilical circulations in nonanesthetized, chronic sheep preparations from 47 to 155 days of gestation. In all cases, ammonia was excreted from the uteroplacental unit into both the uterine and umbilical circulations. In early gestation (70 days), the gravid uterus excretes into the maternal blood ~55 μol of ammonia/mmole of oxygen consumed and it can be estimated that the ratio of nitrogen excreted by the uterus as ammonia to the combined total nitrogen requirements for both growth and ammonia excretion is ~44%. Late in gestation, the gravid uterus excretes ~16 μmol of ammonia/mmole of oxygen consumed. This represents ~12% of fetal nitrogen requirements.

The effect of beta-receptor-stimulating agents on the utero-placental blood flow.

The influence of salbutamol, a beta-2-receptor-stimulating agent, on the blood flow through the utero-placental unit was evaluated in the human. Serial placenta scintigrams were analysed quantitatively, after injection of 0.5 mCi Indium-113m, by means of a gamma-camera connected on line to a computer. The examinations were performed in the third trimester of pregnancy. No sedation was used. Uterine contractions were not present. Salbutamol caused an increase in activity over the placental region, corresponding to a 15% increase in blood volume. The rise time of the initial phase of isotope accumulation (calculated from 5 to 95% of final activity) was prolonged by 100% during salbutamol infusion. As the rise time is proportional to the volume/flow ratio of blood in the uteroplacental region, our data indicate that salbutamol infusion causes a decrease in blood flow in the absence of uterine contractions.

Uterine prostaglandin E secretion and uterine blood flow in the pregnant rabbit.

Studies were performed in pregnant rabbits to assess the effect of inhibition of prostaglandin synthesis on uterine blood flow. Cardiac output and uteroplacental blood flow (UPBF) were measured using radiolabeled microspheres. Prostaglandin E (PGE) concentration was measured by radioimmunoassay in the uterine vein and peripheral artery of the pregnant nephrectomized rabbit. Either meclofenamate or indomethacin 2 mg/kg were utilized to inhibit prostaglandin synthesis. Systemic arterial pressure increased from 86 mm Hg to 98 mm Hg (P less than0.0001) after prostaglandin inhibition. Cardiac output was unchanged after the inhibition of prostaglandin synthesis, 326 ml/min to 7.8 ml/min. Uterine vein PGE concentration was extremely high, 172.4 ng/ml, with concomitant peripheral arterial PGE 2.1 NG/ML. Intravenous administration of either meclofenamate or indomethacin reduced uterine vein PGE to 23 ng/ml (P less than 0.01) and arterial PGE to 1.0 ng/ml (P less than 0.05). Male and nonpregnant female rabbits had lower arterial PGE, 0.37 ng/ml (P less 0.05). Studies in non-nephrectomized pregnant animals demonstrated that uteroplacental secretion of PGE was greater than five times renal secretion. These studies demonstrate that the rabbit uteroplacental unit is a rich source of PGE and suggest that production of the vasoactive lipid may have a key role in regulating UPBF during pregnancy.

Toxemia of pregnancy: Mechanism and therapeutic management

If toxemia represents impaired perfusion of the uteroplacental unit with failure of compensatory homeostatic mechanisms, measures that adversely affect blood volume and flow would not be expected to benefit the fetus. Clinical experience and investigational evidence have combined to support this axiom, as, for example, in the decline and fall in the use of diuretic agents. On the other hand, because magnesium sulfate has a beneficial effect on uterine blood flow, it continues to be the first major drug of choice in the treatment of toxemia. Although treatment of severe toxemia has resulted in remarkable and laudatory decreases in maternal and perinatal mortality, the prevention of toxemia remains more of an indefinite issue. This issue has taken on a new dimension with the data supporting the importance of diet and protein intake. These remain important sociomedical questions. What is missing for the practitioner is a convenient means of detecting the patient who is destined to have toxemia. If the mechanism of toxemia is activated by impaired uteroplacental perfusion, the process would be expected to develop over a period of time. This is supported by the changes found in dehydroepiandrosterone sulfate clearance before the clinical appearance of hypertension. Accordingly, an understanding of these mechanisms should eventually yield laboratory analyses that would reveal the patient with the pathophysiologic features of toxemia before the clinical signs of hypertension, proteinuria and edema develop.

An essay: Prostaglandins and toxemia of pregnancy

Toxemia is defined in empiric, clinical terms because the pathogenesis and etiology of this complication of pregnancy remain unknown. Toxemia of pregnancy is characterized by the development of edema, hypertension, proteinuria, and a complex of symptoms which may culminate in convulsions. Eclampsia means nothing more than convulsions and coma, therefore the classification of this condition into pre-eclampsia and eclampsia might better give way to mild and severe toxemia, the latter with or without convulsions and/or coma. Hypertension in pregnancy continues to be a major cause of neonatal morbidity and mortality, and probably is a significant factor in cases of central nervous system deficiency because of an inadequate intrauterine environment. Prevention of this condition is preferable to curative attempts after the disease is established. However prevention requires a clear understanding of the causative factors involved in this syndrome, and such explanations are lacking. Toxemia of pregnancy is a condition explained by many theories, and the intention here is not to add a new theory, but to support an old one. Because this clinical condition resembles a toxic state, the concept that the utero-placental unit liberates a toxic substance or substances into the maternal blood stream is not new, dating back to the 18th century; hence the name toxemia.

The effect of pregnancy upon experimental hypertension in the rabbit: Corbit, J. D., Jr.: Am. J. M. Sc. 201: 876, 1941

Although donkey breeding has gained new interest in the past two decades, knowledge about donkey reproduction is still scarce, particularly on jenny pregnancy. The aim of this study was to describe the ultrasonographic and endocrine profiles of the physiological pregnancy in the jenny. The study was performed on 12 pregnancies of 7 Amiata donkeys from Day 10 after ovulation to delivery. Because three pregnancies, respectively at weeks 42, 44, and 45, were considered pathologic and treated pharmacologically, data collected from 2 weeks before diagnosis to the end of pregnancy were removed from the analysis. Average length of the normal pregnancies was 353.4 ± 13.0 days (range, 339–370 days). Timing, dimensions, and development during the first phases of embryonic growth, evaluated using transrectal ultrasound, were similar to that previously described in jennies and mares: first detection of embryonic vesicle was at 11.8 ± 1.3 days of gestation and diameter was 6.5 ± 1.9 mm, loss of spherical shape occurred at 18.5 ± 1.4 days, and embryo and heart beat were first seen at 22.0 ± 1.1 and 25 ± 1.1 days, respectively. The intrauterine growth in the second half of pregnancy, evaluated using the transrectal and transabdominal approach, also showed strong positive correlations, similar to that reported for the mare. The trends of the combined thickness of the utero-placental unit and the echogenicity of the amniotic and allantoic fluids are examples. The diameters (mm) of fetal chest, eye orbit, and aorta increased throughout pregnancy and were 40.6 ± 2.9, 8.7 ± 1.5, and 3.5 ± 0.7, respectively, at week 13, and 190.9 ± 12.0, 21.4 ± 1.5, and 30.6 ± 1.8 at the last evaluation before parturition. In contrast, heart rate decreased as pregnancy progressed. Regression analyses between these parameters and day of gestation were statistically significant (P < 0.001). All fetuses consistently showed some intrauterine activity. Maternal plasma progestagens and estrone sulfate concentrations followed a pattern similar to that seen in mares, although the prepartal progestagen peak was lower in jennies. This study provides a range of ultrasonographic and endocrine values for normal pregnancy in jennies.