Role of ductus venosus in distribution of umbilical blood flow in human fetuses during second half of pregnancy

Color Doppler sonography was used to study umbilical and ductus venosus (DV) flow in 137 normal fetuses between 20 and 38 wk of gestation. Hepatic flows were also evaluated. In all parts of the venous circulation examined, blood flow increased significantly with advancing gestational age. The weight-specific amniotic umbilical flow did not change significantly during gestation (120 +/- 44 ml. min(-1). kg(-1)), whereas DV flow decreased significantly (from 60 to 17 ml. min(-1). kg(-1)). The percentage of umbilical blood flow shunted through the DV decreased significantly (from 40% to 15%); consequently, the percentage of flow to the liver increased. The right lobe flow changed from 20 to 45%, whereas the left lobe flow was approximately constant (40%). These changes are related to different patterns of growth of the umbilical veins and DV diameters. The present data support the hypothesis that the DV plays a less important role in shunting well-oxygenated blood to the brain and myocardium in late normal pregnancy than in early gestation, which leads to increased fetal liver perfusion.     

Echo-Doppler ultrasonographic assessment of resistance and velocity of blood flow in the ductus venosus throughout gestation in fetal lambs

It has been postulated that during fetal hypoxia, the blood flow shunted through the ductus venosus increases and may account for upto 70% of the total umbilical flow. The objectives of the present study were to use ultrasonography to determine the velocities and waveform indices of blood flow in the ductus venosus in the fetal lamb. The ductus venosus of 15 lamb fetuses was evaluated weekly from Days 45 to 143 of gestation (Day 0=day of AI). The Doppler indices measured were: S/D, the systole/diastole ratio; RI, the resistance index; and PI, the pulsatility index. The velocity waveforms studied were: SV, the peak velocity during ventricular systole; D, the peak velocity during ventricular diastole; aV, the lowest forward velocity during atrial contraction; and TAMV, the time-averaged maximum velocity. Doppler indices from Days 52 to 143 were highly correlated: S/D versus PI (r=0.96, P<0.0001), and versus RI (r=0.93, P<0.0001); and PI versus RI (r=0.97, P<0.0001). Velocity indices were also positively correlated: velocity SV versus D (r=0.87, P<0.0001), versus aV (r=0.79, P<0.05), and versus TAMV (r=0.98, P<0.0001); D versus aV (r=0.88, P<0.05), and versus TAMV (r=0.87, P<0.05); and aV versus TAMV (r=0.82, P<0.05). Doppler indices were negatively correlated with SV (r=-0.22, P<0.03); D (r=-0.37, P<0.0001); TAMV (r=-0.32, P<0.05) and with aV (r=-0.67, P<0.05). The mean value of each Doppler index decreased 40% from Days 52 to 73 (e.g., PI from 0.82+/-0.08 to 0.51+/-0.10; P<0.05), with no significant changes thereafter. Mean (+/-S.E.M.) values of velocity indices SV, D, aV, and TAMV rose twofold from Days 60 to 115 of gestation (e.g., SV from 54.4+/-8.8cm/s to 104.9+/-19.7 and aV from 24.8+/-6.9 to 54.9+/-5.9; P<0.05). In conclusion, Doppler ultrasonography facilitated assessment of the blood flow pattern in the ductus venosus in lamb fetuses between Days 52 and 143.     

Blood flow in the umbilical artery in physiological pregnancy

Fetal umbilical artery flow was measured with Doppler ultrasound technique in 206 cases of the uncomplicated pregnancy. Indices A/B and R.I. were calculated. It was shown that vascular resistance in the umbilical artery is decreasing in the normal pregnancy parallel to its development and is manifested by the changes in A/B and R.I. values.     

Patent ductus venosus and dioxin resistance in mice harboring a hypomorphic Arnt allele

The Ah receptor nuclear translocator (ARNT) is the dimeric partner of hypoxia-inducible factors and thus plays a pivotal role in cellular adaptation to low oxygen environments. ARNT is also a dimeric partner for the Ah receptor (AHR), and this complex is essential in regulating the adaptive metabolic response to polycyclic aromatic hydrocarbons. Because of the essential role of ARNT in hypoxia-driven developmental events, it has been difficult to study the physiological significance of AHR.ARNT heterodimers in vivo. To address this issue, we developed a hypomorphic Arnt allele that displayed normal development and allowed the examination of the role of ARNT in AHR biology. In this regard, the AHR is also known to mediate two additional biological processes: the toxicological response to compounds such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin) and the developmental closure of a fetal vascular structure known as the ductus venosus. Although the mechanism of the adaptive pathway has been well described, the mechanism of AHR-mediated signal transduction in the toxic and developmental pathways is not well understood. Liver perfusion studies demonstrated that ARNT hypomorphs have a patent ductus venosus, identical to that observed in the Ahr null mice. Parallel dioxin toxicity studies demonstrated that the ARNT hypomorphs exhibited resistance to the end points of dioxin exposure. Moreover, we observed that toxicity could be segregated from the classical adaptive responses such as P4501A induction. Taken in sum, these experiments demonstrate that ARNT is an essential component of AHR developmental signaling and shed light on the mechanism of dioxin toxicity.     

Blood flow in the umbilical vein in normal pregnancy]

Blood flow through the umbilical vein was measured with Doppler's technique in 206 pregnant women with normal course of pregnancy. Flow rate index, vein diameter and total blood flow per unit of fetal weigh have been calculated. It was found, that the blood flow rate and umbilical vein diameter increase with the growth of the normal pregnancy.     

On the presence of a ductus venosus in the fetal pig in late gestation

Evidence is presented to show that there is a functional bypass in the liver of the fetal piglet between the umbilical vein and the posterior vena cava. Injections of labelled microspheres (14 micrometer) into the umbilical vein in six fetuses in late gestation resulted in the appearance of radioactivity in the arterial blood and throughout the tissues of all piglets. About 60% of the umbilical venous blood bypassed the liver whereas in a fetal foal, injection in a similar manner, no evidence for a shunt was found. Radiographic studies confirmed the presence of a large vascular connection, equivalent to the ductus venosus, between the umbilical vein and posterior vena cava in the fetal piglet.     

Velocity profiles in the human ductus venosus: a numerical fluid structure interaction study

The veins distributing oxygenated blood from the placenta to the fetal body have been given much attention in clinical Doppler velocimetry studies, in particular the ductus venosus. The ductus venosus is embedded in the left liver lobe and connects the intra-abdominal portion of the umbilical vein (IUV) directly to the inferior vena cava, such that oxygenated blood can bypass the liver and flow directly to the fetal heart. In the current work, we have developed a mathematical model to assist the clinical assessment of volumetric flow rate at the inlet of the ductus venosus. With a robust estimate of the velocity profile shape coefficient (VC), the volumetric flow rate may be estimated as the product of the time-averaged cross-sectional area, the time-averaged cross-sectional maximum velocity and the VC. The time average quantities may be obtained from Doppler ultrasound measurements, whereas the VC may be estimated from numerical simulations. The mathematical model employs a 3D fluid structure interaction model of the bifurcation formed by the IUV, the ductus venosus and the left portal vein. Furthermore, the amniotic portion of the umbilical vein, the right liver lobe and the inferior vena cava were incorporated as lumped model boundary conditions for the fluid structure interaction model. A hyperelastic material is used to model the structural response of the vessel walls, based on recently available experimental data for the human IUV and ductus venous. A parametric study was constructed to investigate the VC at the ductus venosus inlet, based on a reference case for a human fetus at 36 weeks of gestation. The VC was found to be \(0.687\,\pm \,0.023\) (Mean \(\pm \) SD of parametric case study), which confirms previous studies in the literature on the VC at the ductus venosus inlet. Additionally, CFD simulations with rigid walls were performed on a subsection of the parametric case study, and only minor changes in the predicted VCs were observed compared to the FSI cases. In conclusion, the presented mathematical model is a promising tool for the assessment of ductus venosus Doppler velocimetry.     

An assessment of ductus venosus tapering and wave transmission from the fetal heart

Pressure and flow pulsations in the fetal heart propagate through the precordial vein and the ductus venosus (DV) but are normally not transmitted into the umbilical vein (UV). Pulsations in the umbilical vein do occur, however, in early pregnancy and in pathological conditions. Such transmission into the umbilical vein is not well understood. In particular, the effect of the impedance changes in the DV due to its tapered geometry is not known. This paper presents a mathematical model that we developed to study the transmission of pulsations, originating in the fetal heart, through the DV to the umbilical vein. In our model, the tapered geometry of the DV was found to be of minor importance and the only effective reflection site in the DV appears to be at the DV inlet. Differences between the DV inlet and outlet flow were also found to be minor for medium to large umbilical vein–DV diameter ratios. Finally, the results of a previously proposed lumped model were found to agree well with the present model of the DV–umbilical vein bifurcation.     

Effect of NO, phenylephrine, and hypoxemia on ductus venosus diameter in fetal sheep

To study the regulation of the ductus venosus (DV) inlet in vivo, we measured the effect of vasoactive substances and hypoxemia on its diameter in nine fetal sheep in utero at 0.9 gestation under ketamine-diazepam anesthesia. Catheters were inserted into an umbilical vein and a fetal common carotid artery, and a flowmeter was placed around the umbilical veins. Ultrasound measurements of the diameter of the fetal DV during normoxic baseline conditions [fetal arterial PO(2) (PaO(2)) 24 mmHg] were compared with measurements during infusion of sodium nitroprusside (SNP; 1.3, 2.6, and 6.5 microg. kg(-1). min(-1)) or the alpha(1)-adrenergic agonist phenylephrine (6.5 microg. kg(-1). min(-1)) into the umbilical vein or during hypoxemia (fetal Pa(O(2)) reduced to 10 mmHg). SNP increased the DV inlet diameter by 23%, but phenylephrine had no effect. Hypoxemia caused a 61% increase of the inlet diameter and a distension of the entire vessel. We conclude that the DV inlet is tonically constricted, because nitric oxide dilates it but an alpha(1)-adrenergic agonist does not potentiate constriction. Hypoxemia causes a marked distension of the entire DV.     

Neurturin-GFRalpha2 signaling controls liver bud migration along the ductus venosus in the chick embryo

During chick liver development, the liver bud arises from the foregut, invaginates into the septum transversum, and elongates along and envelops the ductus venosus. However, the mechanism of liver bud migration is only poorly understood. Here, we demonstrate that a GDNF family ligand involved in neuronal outgrowth and migration, neurturin (NRTN), and its receptor, GFRalpha2, are essential for liver bud migration. In the chick embryo, we found that GFRalpha2 was expressed in the liver bud and that NRTN was expressed in the endothelial cells of the ductus venosus. Inhibition of GFRalpha2 signaling suppressed liver bud elongation along the ductus venous without affecting cell proliferation and apoptosis. Moreover, ectopic expression of NRTN perturbed the directional migration along the ductus venosus, leading to splitting or ectopic branching of the liver. We showed that liver buds selectively migrated toward an NRTN-soaked bead in vitro. These data represent a new model for liver bud migration: NRTN secreted from endothelial cells functions as a chemoattractant to direct the migration of the GFRalpha2-expressing liver bud in early liver development.     

Blood constituents during the estrous cycle and early pregnancy in dairy cows

The objective of this study was to determine if maternal platelet count, white blood cell count or other blood constituents undergo sustained alterations in concentration following fertilization. Blood samples from 17 Holstein females were collected over an 18-d period starting at estrus. Blood was analyzed for levels of platelets, white blood cells, red blood cells, hemoglobin and hematocrit. Results were analyzed for differences between nonpregnant and pregnant groups. Analysis of variance revealed a day-by-group interaction in the platelet count (P<0.01). White blood cell count showed both a day-by-group interaction and a difference between days (P<0.01). Red blood cell count, hematocrit and hemoglobin levels resulted in no significant difference between the two groups (P>0.05). While statistically significant differences were observed in platelet and white blood cell count, neither of these were sustained over a period longer than 2 d.     

Transrectal Doppler sonography of uterine blood flow during early pregnancy in mares

Transrectal color Doppler sonography was used for the noninvasive investigation of uterine blood flow in five mares. Both the left and right uterine arteries were scanned to obtain blood flow velocity waveforms during two consecutive estrous cycles and two early pregnancies in each mare. Blood flow was expressed as the time-averaged maximum velocity (TAMV) and the resistance index (RI). In all pregnancies the embryonic vesicle could be detected for the first time on Day 11 (day of ovulation: Day 0). No differences in mean TAMV and RI values of both uterine arteries were observed in comparison to the corresponding days of the estrous cycle until Day 11 of pregnancy (P>0.05). From Day 11 onwards, mean TAMV values were higher and mean RI values lower in pregnant mares than in cyclic mares (P<0.05). During the estrous cycle TAMV and RI values did not differ between the right and left uterine arteries (P>0.05). From Days 15 to 29 of pregnancy, TAMV values were consistently higher and RI values lower in the uterine artery ipsilateral to the conceptus and they had a more distinct rise and decline, respectively, compared to the contralateral uterine artery (P<0.05). The variance component estimates for the effect of mare on TAMV and RI values during pregnancy were 60 and 53%, respectively, and for the effect of day of pregnancy, they were 29 and 34%, respectively (P<0.0001). Within mares there were no significant differences between the two pregnancies with regard to blood flow (P>0.05). The results show that uterine blood supply increases in mares during the second week of pregnancy compared to cyclic mares. Furthermore there are individual variations in blood flow between mares.     

Blood flow in skeletal muscles of chicken in the embryonic and early postembryonic periods

In chicken Leghorn, blood flow volume speed in pectoralis and gastrocnemius muscles was measured on 15 and 19 day-old embryos and at the 1st and the 10th days alter hatching. It was revealed that in the last quarter of embryogenesis BF in muscles did not vary remaining in both muscles in identical limits. Similar BF parameters in pectoralis and gastrocnemius muscles and their age-dependent dynamics were observed at embryos with the detained development (with the body weight 2-fold less than the norm). After hatching, the blood flow in both muscles was grown, on the average, 2.4-fold and remained high by the 10th day, a little decreasing in the pectoralis muscle. It was shown, that increase of a muscular blood flow after hatching was accompanied by different changes of anatomic lumen of the arteries addressed in pectoralis and gastrocnemius muscles: in the former it decreased, in the latter--increased.     

Evidence for a role of prostaglandin I2 and thromboxane A2 in the ductus venosus of the lamb

The prostaglandin (PG) endoperoxide, PGH2, and the thromboxane (TX) A2 analog, 9,11-epithio-11,12-methano-TXA2, were tested in vitro on the ductus venosus sphincter from fetal (premature and mature) and neonatal (1-day-old) lambs. PGH2 relaxed the indomethacin-contracted fetal ductus in a dose-dependent manner and its action was reduced after treatment with 15-hydroperoxyarachidonic acid. In contrast, reduced glutathione did not affect the PGH2 relaxation in the indomethacin-treated ductus, nor did it modify the response of the untreated ductus to constrictor stimuli. Unlike PGH2, the stable 9 alpha,11 alpha-epoxymethano-PGH2 analog contracted the vessel. Similarly, the TXA2 analog was a contractile agent, its action exceeding that of the PGH2 analog in potency and efficacy. The TXA2 analog was active on preparations from both premature (minimum 117 days gestation) and mature lambs, but a maximal effect was attained during the perinatal period. These results confirm the existence of a PG-mediated relaxing mechanism in the ductus venosus and suggest that the active compound is PGI2. This mechanism is likely responsible for keeping the ductus patent in the fetus. TXA2, formed within the liver parenchyma, is well suited for playing a role in postnatal closure of the vessel.     

Blood flow in the brain and liver of chicken in embryonal and early postembryonal periods

In chicken Leghorn, blood flow volume speed (BF, laser-Doppler flowmetry) in the brain hemispheres and in liver was measured on days 10, 14, and 19 of embryogenesis and on day 4 after hatching (in experiments on late embryos and chickens, urethane narcosis was used). It was revealed, that initial BF in investigated organs was 2-fold lower than earlier measured in skeletal muscles. In the liver, low BF remained at all periods, but it grew 5-fold greater after hatching. In the brain hemispheres, the BF during this period grows gradually reaching 4-fold size in chickens. It was shown that blood stream increase in the brain was accompanied by uniform increase in anatomic lumen of internal carotid artery; thus settlement sizes of linear speed of blood flow and wall shear stress remain in it at the same level. Lumen extension of celiac artery during the observation period lags behind increases in a blood stream of in it that leads to increase in it of the named parameters.     

Oxidative stress early in pregnancy and pregnancy outcome

The objectives of this study were to determine whether oxidative stress early in pregnancy influenced pregnancy outcome. A combination of assays were used for exogenous and endogenous anti-oxidants together with two well accepted biomarkers for oxidative stress, the urinary excretion of 8-iso-PGF_2α (a biomarker marker for lipid oxidation, n=508) and 8-oxo-7,8 dihydro-2 deoxyguanosine (8-OHdG, a biomarker for DNA oxidation, n=487). The two biomarkers tracked different pregnancy outcomes. Isoprostanes were associated with an increased risk of pre-eclampsia and a decreased proportion of female births. In contrast, 8-OHdG tracked lower infant birthweight and shortened gestation duration. Birth defects were associated with low levels of 8-OHdG.