The blood flow to the pregnant uterus is of evident importance in supplying to the fetus the raw materials required for its growth and development and in removing from the fetal environment the waste products of metabolism. Description of the uterine blood supply was largely in anatomical terms until Barcroft and co-workers measured it directly in the rabbit (1), and indirectly in the sheep (2). It has also been calculated in the sheep (3, 4) from data obtained by fetal plethysmography (5). METHODS I. TheoryEstimation of human uterine blood flow at term has awaited the development of methods other than those used in animals. Recently, attempts (6, 7) have been made to apply the Fick principle (8) to the study of the maternal uterine circulation. Figure 1 presents this principle. It is modified from a derivation published by Kety (9) in a discussion of cerebral blood flow. This equation is applicable to any organ if (a) the amount of some blood-borne substance X taken up (or released) in a known time interval by that organ can be determined and if (b) the concentrations of substance X in blood entering and blood leaving the organ can be determined over the same period of time.The most familiar application of the Fick equation is in the determination of cardiac output. Here, since the blood flow to all body tissues is being studied, the oxygen consumption of the body may be used as the numerator of the equation and the difference in oxygen content between arterial and "mixed" venous blood is used as the denominator. The ideal test substance for use in the study of an individual organ is a blood-borne metabolite, the rate of production or destruction of which by that organ is measurable and the concentration of which in blood going to that organ and in mixed venous blood leaving that organ can be determined. As an example, hepatic blood flow has been calculated from knowledge of (a) the difference in concentrations of urea in blood entering and blood leaving the liver and (b) the rate of formation of urea, a process limited to the liver (10).Kety (9) has used a foreign substance, nitrous oxide gas, for determination of cerebral blood flow by the Fick principle. This substance is normally not present in the body and is not metabolized in body tissues. The method can be applied to the uterus if the amount of nitrous oxide in the uterus at the end of the experiment can be determined and if the concentrations of nitrous oxide in arterial blood supplying and venous blood draining the uterus during the experiment can be measured. For such an application the equation derived above ( Figure 1) would be modified to the following:Uterine Blood Flow N20 in uterus (N20) artery -(N20) uterine vein (Equation 1) The numerator consists of the total nitrous oxide content of the uterus and its contents at the end of the period of nitrous oxide inhalation. The denominator is the integrated arteriovenous nitrous oxide difference during the period of nitrous oxide inhalation. II. ProcedureObservations leading to an estimation of uteri...

Combining a vacuum extraction method with gas chromatography makes possible accurate, reproducible determination of small quantities of permanent gases contained in biological fluids. One useful application is demonstrated by determining the oxygen tension in 1 ml of human plasma.

Investigation of the properties of indigo carmine reveals that it may be more suitable than the dye, T-1824, for circulatory studies that are now commonly carried out using the dye dilution principle of Stewart and Hamilton. Comparison is made of simultaneous dilution curves of indigo carmine and radioactive iodinated serum albumin. Apparently, indigo carmine is bound to protein firmly enough to remain the plasma in one passage through the heart and lungs, but not too firmly to be extracted rapidly from the plasma by excretory systems in the kidney and liver. This allows repeated injections without accumulation.

Simultaneous indicator dilution curves of albumin I 131 , tritiated water, and an inert gas are identical when the indicators do not traverse a capillary bed. When the same three indicators traverse the pulmonary capillaries before sampling, the shapes of the tritiated water and inert gas dilution curves are altered by movement of these two indicators into an extravascular water space and gas space respectively. The arithmetical difference between the distribution volumes of albumin I 131 and tritiated water measures a functional extravascular water space in the lungs. The difference between tritiated water and inert gas distribution volumes is a measure of a lung gas volume in contact with perfusing capillaries. Pericapillary water distribution volume in normal dogs was found to be 4.2 ± 0.8 ml/kg and the gas distribution volume 24 ± 6 ml/kg. In normal human subjects the respective values were 1.1 ± 0.3 ml/cm height and 1.80 ± 0.28 liters/m 2 of body surface area. Changes in both gas and water distribution volumes were observed as a result of experimental pulmonary edema in dogs and in various forms of pulmonary disease in man.

To evaluate the effect of diffusion on the pulmonary extravascular water volume determined from indicator dilution studies, simultaneous comparisons of the pulmonary extravascular distribution volumes of tritiated water (THO) and of three lipid soluble substances with higher molecular weights were made. In 21 studies on pentobarbital-anesthetized dogs, the distribution volume of antipyrine (AP) was slightly smaller tlian that of THO (mean difference = 2.86 ml ± 1.49 SE ; 0 . 1 > P > 0 . 0 5 ) . The results of 21 studies in conscious humans showed a slightly smaller distribution volume for 131 Iiodoantipyrine (IAP) than for THO (mean difference = 15.62 ml it 3.36 SE; P < 0 . 0 1 ) . Neither the differences between THO and AP in dogs nor those between IAP and THO in humans correlated with either flow (r = 0.25 for dog studies; r = 0.07 for human studies) or the mean transit time of the intravascular indicator (r = -0.17 for dog studies; r = 0.14 for human studies). No significant difference between the distribution volume of 14 C-ethanol (ETOH) and THO could be shown in either dogs (12 studies) or humans (15 studies). Relative lung-to-blood partitioning of IAP as compared to THO at equilibrium in dogs was 0.92 ±0.08; the same value for ETOH was 1.18 ± 0.10. The findings strongly suggest that distribution volume for these indicators is independent of their diffusion characteristics and that IAP may be a reasonable substitute for THO in measuring pulmonary extravascular water volume.