A method is described for the simultaneous estimation of uterine and umbilical blood flows and oxygen uptakes. A test stubstance, antipyrine, was infused at constant rate in the fetal circutlation. About 50 min. after starting the infusion a steady state was attained in which the rate of transplacental diffusion of the test substance was equal, blut for small corrections, to the rate of infusion. During the steady state, blood samples were collected from uterine and umbilical arteries and veins and analyzed for antipyrine and oxygen. Flows and oxygen uptakes were calculated according to Fick's principle. Thie results of sixteen experiments on sheep and goats sh1ow that: (1) transplacental diffusion of antipyrine is mainly flow‐limited, (2) the placenta simulates a concturrent system of exchange, and (3) the oxygen uptakes of the fetus and the utero‐placental mass were, in many cases, of similar magnitude.

A method is described for the introduction of plastic catheters into the umbilical vessels of fetal goats and lambs whereby samples of blood may be obtained over a period of days and weeks in conditions in which the mother is free from obvious stress. The results of the analyses of samples so obtained, indicate that (1) the oxygen capacity of the fetal blood does not increase after 100 days and (2) that the oxygen saturation does not fall systematically in the last month of gestation. Data on the day to day variations in the blood levels of oxygen, carbon dioxide and pH are reported.ENCOURAGED by our success with the use of indwelling plastic catheters for sampling the arterial and uterine venous bloods of pregnant ewes, at selected intervals, as gestation advances [Meschia et al., 1959] we began in 1958 to explore the possibility that we might obtain, in the same way, blood samples for analysis from the umbilical circulation without interfering with the normal growth and development of the fetus, its natural birth at full term and subsequent survival. We were prompted to do so for we were aware that all of our studies on the exchange of metabol.ites across the placental barrier between mother and fetus were open to the criticism that the blood samples, which formed their basis, were obtained after the mother had been anesthetized and restrained, the uterus exposed and incised, before the fetus -or a loop of the umbilical cord -was delivered.Of how far these procedures affected the levels of the metabolites in the fetal blood under study, their transplacental differences in concentration, and the properties of the placental barrier, we had no knowledge. But in some instances, our procedures did initiate changes in the uterus and the placenta which were clearly incompatible with the continued survival of the fetus, though the well recognized capacity of the fetal heart to endure hypoxia frequently served to mask that fact temporarily. In other circumstances, the conditions in which the fetal blood samples were drawn appeared * U.S.P.H. Fellow. Present Address:

Estimates have been made of: (1) the oxygen tension in blood samples drawn from unanesthetized ewes and their fetuses via chronic catheters in the uterine vein, umbilical artery and umbilical vein between 90 days and full term; (2) the rate of oxygen uptake by the umbilical circulation between 80 and 134 days in a series of anesthetized ewes, and (3) the 'diffusing capacity' of the placenta for oxygen in eleven anesthetized ewes in stages of gestation from 81 to 134 days. The results demonstrate: (1) there is no regular change with advancing gestation in the oxygen tension of the blood in the vessels sampled, and (2) the quantity of oxygen taken up by the umbilical blood and the 'diffusing eapacity' of the placenta for oxygen both increase as the fetal weight.As we explained earlier our interest in the permeability of the placenta of the ewe to oxygen, in the period 80 days to full term, grew out of two conflicting lines of evidence. One suggests that the permeability of the placenta and the weight of the cotyledons both reach a maximum about 100-110 days, the other that the permeability to oxygen increases with the fetal requirements as gestation advances beyond the 100th day. Data bearing on the question have been obtained through observations on: (1) the transplacental difference in oxygen tension; (2) the rate at which oxygen crosses the placenta relative to the fetal weight, and (3) the 'diffusing capacity' of the placenta for oxygen. These data are complementary and taken together support the second alternative. MATERIAL AND METHODS(1) The Transpiacental Difference in Oxygen Tension. -Pure bred Dorset ewes, at known stages in gestation, were used in all the experiments reported here. The uterine and umbilical bloods for the estimation of the transplacental difference in P02 were obtained via indwelling catheters [Meschia et at., 1959;.For each estimation two samples were drawn from a single vessel, one of 1-6 ml. into 0-4 ml. of an isotonic heparin-fluoride mixture, a second of 2 ml. (4 ml. from a maternal vessel) into an oiled glass syringe. The pH of the first was measured at room temperature with a glass electrode and a Beckman meter (model G); the result was corrected to 380 by subtracting 0*015 pH units for each degree below 380 at which the measurement was made. The oxygen content of the second sample was determined in duplicate on 0*5 ml. with the Van Slyke-Neil apparatus. The oxygen capacity was.calculated from the optical density at 530 my, of blood diluted 1 to 250 parts with distilled water and alkalinized with ammonia. The colorimeter was standardized with sheep blood saturated with oxygen in a Barcroft tonometer before the content * U.S.P.H. Fellow -present address: