The preeclampsia condition alters external potassium-evoked contraction of human umbilical vessels.

INTRODUCTION: Pre-eclampsia (PE) is a disease of high incidence in parturients, that adversely affects both mother and fetus. Although PE prevalence is high, there are few studies on literature describing its etiology or its mechanism of action. Thus, the aim of this study was to elucidate PE-induced alterations of contractile reactivity in umbilical vessels. METHOD: Segments of human umbilical artery (HUA) and human umbilical vein (HUV) from neonates of normotensive or PE parturients were obtained and contractile responses measured with a myograph. The segments were allowed to stabilize (2 h) under 1.0, 2.0 and 3.0 g force (gf) at pre-stimulation and, then, were stimulated with high isotonic K+ concentrations ([K+]o; 10-120 mM). RESULTS: All preparations responded to increases in isotonic K+ concentrations. In HUA and HUV of neonates of normotensive parturients, and in HUV of neonates of PE parturients, the contraction saturated at nearly 50 mM [K+]o, while in HUA of neonates of PE parturients, saturation occurred at 30 mM [K+]o. Additionally, several differences between contractile responses of HUA and HUV from neonates of normotensive parturients and those from neonates of parturients with PE were observed. PE alters the contractile response of the HUA and HUV to increased [K+]o, and its contractile modulation by the pre-stimulus basal tension. Moreover, in HUA of PE, reactivity is decreased for 2.0 and 3.0 gf basal tensions and increased for 1.0 gf; in the HUV of PE condition, it is increased for all basal tensions. DISCUSSION: In conclusion, PE promotes several alterations in HUA and HUV contractile reactivity, vessels in which important circulatory alterations are known to occur.

Umbilical vein blood flow: State-of-the-art.

Placental blood supply to the fetus can be measured by evaluating the umbilical vein blood flow. Despite its potential application in healthcare, the umbilical vein blood flow volume is still used only in research setting. One of the reasons is a concern regarding its reproducibility, partly due to technology issues. Nowadays, technology improvements make this evaluation accurate and reproducible. The aim of this review is to refresh basic elements of the physiology of umbilical vein blood flow and its analysis. Its evaluation in normal and abnormal fetal growth is also discussed.

Evaluation of midtrimester ductus venosus diameter and peak systolic velocity to predict late onset small for gestational age fetuses.

OBJECTIVE: The ductus venosus, a small blood vessel in the fetal venous system, has extraordinary physiologic significance because it connects the umbilical vein to the inferior vena cava in the fetus circulation system and transports highly oxygenated blood from the placenta to the fetus' heart. Hence, assessment of ductus venosus flows is helpful in evaluating fetal hemodynamics. Considering the critical function of the ductus venosus, we hypothesized that the diameter of the midtrimester ductus venosus and its peak velocity index can be related to adequate fetal growth; therefore, the aim of this study was to evaluate the role of the midtrimester umbilical venous blood flow, ductus venosus diameter, and ductus venosus peak systolic velocity to help predict uncomplicated deliveries of late onset small for gestational age (SGA) fetuses. METHODS: In this prospective study we analyzed the pregnancies and deliveries of 398 pregnant women who met the inclusion criteria and divided them into three groups according to fetal birth weight as follows: birth weight <3 percentile SGA group (n = 16), birth weight 3-10 percentile SGA group (n = 42), and appropriate for the gestational age (AGA) group (n = 340). The midtrimester ductus venosus diameter and peak sistolic velocity, umbilical venous blood flow, and umbilical artery pulsatility index (PI) were recorded. In the absence of congenital anomalies, the diagnosis of fetal growth restriction (FGR) is made according to Delphi consensus criteria. In the absence of abnormal Doppler findings, late FGR was defined as occurring ≥32 weeks. RESULTS: Maternal age, nulliparity, mean gestational age at ultrasound evaluation, ethnicity, body mass index, and previous cesarean delivery rates were similar among the groups. In addition, mid-trimester fetal biometric measurements and amniotic fluid volume were similar among the groups. The gestational age at delivery, prematurity, fetal birth weight, vaginal delivery rates, and rate of admission to the neonatal intensive care unit were significantly different among the groups. The mean mid-trimester umbilical vein blood flow to abdominal circumference ratio (UVBF/AC) was similar among the groups (p=.740). In the <3 group, the mean peak systolic velocity of the ductus venosus was significantly lower and the mean diameter of the ductus venosus significantly higher than those in the 3-10 and AGA groups (both p<.001). Although the values are below the 95th percentile mid-trimester umbilical artery PI was significantly higher in the <3 percentile SGA group than in the 3-10 percentile SGA and AGA groups. CONCLUSION: Our results suggest that the diameter and peak systolic velocity of the mid-trimester ductus venosus are useful noninvasive measurements that provide prediction of late onset SGA fetuses.

Effect of breathing on venous return during delayed cord clamping: an observational study.

OBJECTIVE: To investigate the effect of spontaneous breathing on venous return in term infants during delayed cord clamping at birth. METHODS: Echocardiographic ultrasound recordings were obtained directly after birth in healthy term-born infants. A subcostal view was used to obtain an optimal view of the inferior vena cava (IVC) entering the right atrium, including both the ductus venosus (DV) and the hepatic vein (HV). Colour Doppler was used to assess flow direction and flow velocity. Recordings continued until the umbilical cord was clamped and were stored in digital format for offline analyses. RESULTS: Ultrasound recordings were obtained in 15 infants, with a median (IQR) gestational age of 39.6 (39.0-40.9) weeks and a birth weight of 3560 (3195-4205) g. Flow was observed to be antegrade in the DV and HV in 98% and 82% of inspirations, respectively, with flow velocity increasing in 74% of inspirations. Retrograde flow in the DV was observed sporadically and only occurred during expiration. Collapse of the IVC occurred during 58% of inspirations and all occurred caudal to the DV inlet (100%). CONCLUSION: Spontaneous breathing was associated with collapse of the IVC and increased antegrade DV and HV flow velocity during inspiration. Therefore, inspiration appears to preferentially direct blood flow from the DV into the right atrium. This indicates that inspiration could be a factor driving placental transfusion in infants.

Protein Micropatterning in 2.5D: An Approach to Investigate Cellular Responses in Multi-Cue Environments.

The extracellular microenvironment is an important regulator of cell functions. Numerous structural cues present in the cellular microenvironment, such as ligand distribution and substrate topography, have been shown to influence cell behavior. However, the roles of these cues are often studied individually using simplified, single-cue platforms that lack the complexity of the three-dimensional, multi-cue environment cells encounter in vivo. Developing ways to bridge this gap, while still allowing mechanistic investigation into the cellular response, represents a critical step to advance the field. Here, we present a new approach to address this need by combining optics-based protein patterning and lithography-based substrate microfabrication, which enables high-throughput investigation of complex cellular environments. Using a contactless and maskless UV-projection system, we created patterns of extracellular proteins (resembling contact-guidance cues) on a two-and-a-half-dimensional (2.5D) cell culture chip containing a library of well-defined microstructures (resembling topographical cues). As a first step, we optimized experimental parameters of the patterning protocol for the patterning of protein matrixes on planar and non-planar (2.5D cell culture chip) substrates and tested the technique with adherent cells (human bone marrow stromal cells). Next, we fine-tuned protein incubation conditions for two different vascular-derived human cell types (myofibroblasts and umbilical vein endothelial cells) and quantified the orientation response of these cells on the 2.5D, physiologically relevant multi-cue environments. On concave, patterned structures (curvatures between κ = 1/2500 and κ = 1/125 µm-1), both cell types predominantly oriented in the direction of the contact-guidance pattern. In contrast, for human myofibroblasts on micropatterned convex substrates with higher curvatures (κ ≥ 1/1000 µm-1), the majority of cells aligned along the longitudinal direction of the 2.5D features, indicating that these cells followed the structural cues from the substrate curvature instead. These findings exemplify the potential of this approach for systematic investigation of cellular responses to multiple microenvironmental cues.

6-Nitrodopamine is released by human umbilical cord vessels and modulates vascular reactivity.

AIMS: Human umbilical cord vessels (HUCV) release dopamine and nitric oxide (NO). This study aims to verify whether HUCV release nitrocatecholamines such as 6-nitrodopamine (6-ND). MAIN METHODS: Liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) was used to identify 6-ND release from HUCV rings incubated in Krebs-Henseileit's solution. Vascular reactivity of HUCV rings was tested (with and without endothelium integrity) by suspension of the rings in an organ bath under isometric tension and application of 6-ND and other known mediators. KEY FINDINGS: LC-MS/MS revealed a basal release of 6-ND from endothelium intact from both human umbilical artery (HUA) and vein (HUV). The endothelium intact release was inhibited by the pre-treatment with NO synthesis inhibitor L-NAME (100 µM). In contrast to dopamine, noradrenaline and adrenaline, 6-ND did not contract HUCV, even in presence of L-NAME or ODQ. 6-ND (10 µM) produced a rightward shift of the concentration-response curves to dopamine (pA2: 5.96 in HUA and 5.72 in HUV). Contractions induced by noradrenaline and adrenaline were not affected by pre-incubation with 6-ND (10 µM). In U-46619 (10 nM) pre-contracted endothelium intact tissues, 6-ND and the dopamine D2-receptor antagonist haloperidol induced concentration-dependent relaxations of HUA and HUV. Incubation with the dopamine D1-receptor antagonist SCH-23390 (10 nM) abolished relaxation induced by fenoldopam but did not affect those induced by 6-ND. SIGNIFICANCE: 6-ND is released by HUCV and acts as a selective dopamine D2-receptor antagonist in this tissue. This represents a novel mechanism by which NO may modulate vascular reactivity independently of cGMP production.

Reliability and characteristics of ultrasound measurement of fetal umbilical venous blood flow volume according to the site of measurement.

PURPOSE: This study aimed at assessing the reliability and characteristics of fetal umbilical venous blood flow volume (UVFV) measurement using ultrasound. METHODS: We conducted a prospective study at our center from November 2017 to July 2019. We performed transabdominal ultrasound examinations at 18-34 weeks' gestation in uncomplicated singleton pregnancies. UVFV was calculated using vessel diameter (D) and maximum flow velocity (V) as follows: (D/2)2 × π × V × 0.5 × 60 (Q, mL/min). Two examiners measured each value three times in the free-loop (FL) and intra-abdominal (IA) portions of the umbilical vein. Intra-rater and inter-rater reliability was evaluated by intraclass correlation coefficient (ICC) and a Bland-Altman plot. RESULTS: Two hundred and eight cases were measured by two examiners. The rate of complete measurement at FL and IA was not significantly different (88.5% vs. 79.3%, respectively; p = 0.113). The intra-rater reliability of D and V was high at FL and IA. Regarding inter-rater reliability, the ICC of D, V, and Q was 0.973, 0.582, and 0.963 at FL, and 0.994, 0.912, and 0.989 at IA, respectively. A Bland-Altman plot showed that D and V had greater standard deviation at FL than IA. Regarding Q, the standard deviation at FL was also larger than at IA, and measurement variance at FL increased as the measured value increased, but that at IA did not. CONCLUSION: UVFV measurement showed high intra-rater and inter-rater reliability at FL and IA, but the variance of measurements at FL became large as the measured value increased. Properties of different measurement sites should be considered when evaluating UVFV.

Variation of the maximum velocity along the umbilical vein supports the Reynolds pulsometer model.

OBJECTIVE: To challenge, with a modern sonographic approach and a numerical model, the Reynolds's concept which suggests that the vascular structure of the umbilical cord could act as a pulsometer facilitating the venous return to the foetus. METHOD: Forty-five patients between 20 and 28 weeks of gestation were included in the study. The blood maximum velocity in the umbilical vein, measured at both foetal and placental ends, was assessed. Several sonographic parameters of the cord, including the diameter of the umbilical vein at both extremities, cord cross-sectional area and Wharton's jelly section surface were measured. We compare our data with those of a numerical model. RESULTS: A difference in maximum velocity between the two extremities of the umbilical vein (ΔUVVmax) was noted. The maximum velocity was significantly higher at the foetal umbilical end (14.12 +/-3.18 cm/s) than at the placental end (11.93 +/-2.55 cm/s; p < 0.0001). The mean difference is 2.2 +/- 2.3 cm/s. No difference in the umbilical vein diameter was measured at both cord ends (umbilical 4.85 +/-0.9 mm, placental 4.86 +/-0.87 mm, p < 0.0001). There is no significant relationship between ΔUVVmax and the cord cross-sectional area or Wharton's jelly index. CONCLUSION: Modifications of the spatial velocity profile together with the pulsometer model could explain the maximum velocity changes that is measured in the umbilical vein along the cord. This numerical model consolidates the sonographic observations.