Observations on unrestrained nonpregnant ewes, prepared with appropriately placed indwelling catheters for obtaining blood samples, indicate that the administration of oestrogen -either I.M. or I.V. -is followed by a fall in the coefficient of 02 utilization of the uterus, and an increase in the blood flow through it, that were often detectable 30 min later and approached minimum and maximum values respectively after about an hour and a half. Similar results were obtained in acute experiments at which the uterine blood flow was measured directly and the oxygen consumption (ml./kg/min) determined. In all of the acute experiments the blood flow increased after oestrogen administration in the absence of any regular increase in 02 consumption. In three experiments the flow rate (ml./kg/min) increased about fivefold.The results of our earlier estimates of blood flow to, and oxygen consumption of, the uterus of the nonpregnant ewe, studied whilst standing unrestrained in a small crate [Huckabee et al., 1968] demonstrated that in these circumstances the blood flow varies widely from animal to animal and without any apparent relation to the oxygen consumption. There appeared, however, to be a correlation between the appearance of the ovaries and uterus and the rate (ml./kg/min) at which the uterus was perfused. The lowest flows and the widest (A-V) 02 differences were observed in ewes in which at least one ovary contained a large protruding corpus luteum at laparotomy two or three days prior to the estimation of the flow, whereas the highest flows and lowest (A-V) 02 differences were obtained in ewes in which one or both ovaries contained large follicles at that time.If, as seems likely, the appearance of the ovaries and the uterus was an index of the blood levels of the ovarian hormones, our observations suggest that these levels, rather than the oxygen consumption of the uterus (ml./kg/min), were the primary determinants of the uterine blood flow. They drew our attention to the need for data on the effect of increasing the blood levels of ovarian hormonles on the flow of uterine blood (ml./kg/min) and on oxygen consumption.

The concentrations of ovine placental lactogen (oPL) have been determined in maternal plasma, umbilical cord plasma, and allantoic fluid by an homologous radioimmunoassay for oPL which is sensitive to 0-1 ng hormone. Ovine placental lactogen was first detected in maternal plasma at 41-50 days of gestation and reached a peak concentration of 2547 +/- 226 (S.E.M.) ng/ml at 121-130 days in ewes with singleton gestations. The oPL concentration in cord plasma was 336-4 +/- 60-3 ng/ml and in allantoic fluid was 29-6 +/- 6-4 ng/ml. After surgical removal of the placenta, oPL disappeared from maternal plasma with a half-life of 29-1 +/- 1-3 min.

Experiments were carried out to test the applicability of the 'diffuLsion equilibrium' tecimique to the estimation of the rate of umbilical blood flow in unstressed ewes and does (female goats) in the last third of gestation. Antipyrine was infused into the maternal circulation for 5-7 min. whilst the concentration difference across the umbilical circuit was followed for 30 min. during which it rose and then fell to insignificance. A comparison of the concentrations of antipyrine in umbilical blood and fetal tissue at the 30th min. indicated such a degree of agreement that blood concentration can be substituted for tissue concentration as the numerator in the equation expressing the Fick principle. Results of the application of the method in both acute and chronic experiments are presented, together with data on the v-a oxygen difference across the uimbilical circuit and the oxygen consumption of the fetus ini utero.THE demonstration that blood samples can be obtained via plastic catheters in the umbilical vessels of fetal sheep and goats at intervals over periods of days and weeks without interference with their normal development or natural birth b] led us to investigate the possibility of estimating the rate of umbilical blood flow by the Fick principle using the diffusion-equilibrium technique of Kety and Schmidt [1948] as modified by Huckabee and Walcott [1960] for blood flow studies on skeletal muscle. If this method can be applied to the umbilical circulation the way is open for studies of the metabolic rate of the fetus in 'stress free' circumstances and without terminating the pregnancy.To eliminate the need for the direct determination of the quantity of the test substance -an inert gas or some slowly metabolized material -delivered by the blood to the organ under study, and so the need to weigh that organ, Kety and Schmidt [1948] and Huckabee and Walcott [1960] arranged their procedures so they could estimate the tissue concentration of the test material from its concentration in the venous blood at the end of the period over which the flow was to be determined. This they did by creating, across the organ, an arterio-venous difference of the test substance which diminished gradually to insignificance as the blood and tissue concentrations approached Crenshaw, Huckabee, Curet, Mann and Barron equilibrium in the final minutes of the period of estimation of blood flow. After establishing by experiment that the tissue and blood concentrations were sufficiently close in this period to justify the substitution of the latter for the former, they were able to express the rate of blood flow in millilitres per minute per kilogram of tissue perfused by substituting in the numerator of the Fick equation the blood concentration for the quantity delivered to the tissue. As the rates of umbilical blood flow and fetal metabolism are commonly expressed per kilogram of fetus, this 'diffusion-equilibrium' method appeared to be particularly suited to the estimation of the umbilical blood flow in utero. Accordingly, the ...

Arterial and uterine venous concentrations of alpha amino nitrogen and uterine blood flow were repeatedly measured in twelve non-pregnant and ten pregnant Dorset ewes.The arterial levels and uterine arteriovenous differences of alpha amino nitrogen were low early in gestation and gradually increased to approach non-pregnant values towards the end of gestation. The uterine uptake of alpha amino nitrogen per kilogramme of uterine tissue behaved in a similar way but remained lower than the uptake per kilogramme of tissue by the non-pregnant uterus.The data suggest that the removal of amino acids by the uterus is independent of the levels in the blood reaching the organ.In order to understand the mechanisms that govern the supply of amino acids to the fetus in utero we have thought that a study of the arterial and uterine venous levels and uterine uptake of alpha amino nitrogen might provide useful background information for future work on the transport of amino acids across the placenta. We have carried out such a study on both non-pregnant and pregnant ewes by means of indwelling plastic catheters maintained in the main uterine vein and an artery. In this way continued access to the uterine circulation was secured so that repeated observations could be made on each ewe.We believe that the information thus obtained is reliable as the animals were free of stress and under acceptable physiologic conditions. MATERIALS AND METHODS Thirteen non-pregnant and ten pregnant purebred Dorset ewes were used; breeding dates were obtained by removing the ewe from the ram as soon as she was marked