Uterine Circulation Research Articles

Diverse Mechanisms of Endothelium-Derived Hyperpolarizing Factor-Mediated Dilatation in Small Myometrial Arteries in Normal Human Pregnancy and Preeclampsia1

This ex vivo study focuses on the mechanisms of endothelium-dependent dilatation in the uterine circulation of normal pregnancy (n = 12) and in women with preeclampsia (n = 12). Arteries (internal diameter, ∼250 μm) isolated by myometrial biopsy from women undergoing planned cesarean delivery or delivery as a result of the deterioration of preeclampsia were studied using a wire myograph. Bradykinin-induced dilatation was assessed in the presence and/or absence of pharmacological inhibitors to determine the contribution of nitric oxide and endothelium-derived hyperpolarizing factor (EDHF), as well as that of EDHF-mediated pathways such as myoendothelial gap junctions (MEGJs) and products of arachidonic acid, H(2)O(2) and cytochrome P450 2C9 (CYP2C9). Transmission electron microscopy was used to visualize morphological prerequisites for MEGJs. In normal pregnancy, EDHF through MEGJs appeared to be a predominant mediator conferring endothelium-dependent relaxation in small myometrial arteries. In preeclampsia, bradykinin-induced relaxation was reduced via compromised EDHF-type responses, in which the contribution of MEGJs became negligible. The attenuated role of MEGJs to endothelium-dependent relaxation was partly compensated through the contribution of H(2)O(2) or other endothelium-derived relaxing factors. CYP2C9 products of arachidonic acid had no effect on EDHF-type relaxation in arteries of women with normal pregnancy or with preeclampsia. We suggest that EDHF-type responses via MEGJs are primarily targeted in small myometrial arteries in women with preeclampsia. This could significantly contribute to the impaired uteroplacental blood flow in this disorder.

A longitudinal study of the relationship between maternal cardiac output measured by impedance cardiography and uterine artery blood flow in the second half of pregnancy

To study serial changes in maternal systemic and uterine artery haemodynamics and establish reference ranges for the second half of pregnancy. Prospective longitudinal observational study. University hospital in Norway. Low-risk pregnant women. Fifty-three low-risk pregnancies were evaluated at approximately 4-weekly intervals. Maternal systemic haemodynamics was assessed with impedance cardiography. Uterine artery blood velocity and diameter were measured using Doppler ultrasonography and uterine artery volume blood flow (Q(uta)) was calculated as the product of mean velocity and cross-sectional area of the uterine artery. The fraction of cardiac output (CO) distributed to the uterine circulation was calculated as: Q(uta)/CO x 100. CO, Q(uta), uterine vascular resistance (R(uta)) and the fraction of CO distributed to the uterine circulation. The CO increased (P = 0.0063) until 34 weeks and remained stable until term. Total Q(uta) increased from 299 to 673 ml/minute and R(uta) halved from 0.26 to 0.13 mmHg/ml/minute (P < 0.0001). The fraction of CO distributed to the uterine circulation increased from 5.6% to 11.7% (P < 0.0001). During the second half of pregnancy, Q(uta) and the fraction of maternal CO distributed to the uterine circulation increase approximately two-fold, mainly as a result of decrease in R(uta).

Exercise initiates uterine vasoconstriction in female rats

The rat is a common model used to explore mechanisms of vascular control in exercise and in pregnancy. It is now possible to measure uterine artery blood flow (UtBF) during exercise in rats. We hypothesized that exercise initiates uterine artery vasoconstriction in the nonpregnant rat. Seven female Sprague‐Dawley rats were familiarized with treadmill running and were instrumented with a left carotid artery catheter to measure blood pressure (BP) and an ultrasonic transit‐time probe (Transonic 0.5–0.7 mm PSB) for measurement of right UtBF. Seven to 10 days postsurgery the rats underwent 2 exercise trials at workloads that term pregnant rats are capable of completing: 7 and 13 m/min/6% grade for 5 min. Values are mean (SD). BP [112(21) mmHg] did not change with exercise and exercise HR averaged over min 2–5 [488 (73) bpm] was similar at both workloads. At 7 and 13 m/min, UtBF [0.36 (0.17) ml/min] and uterine artery conductance (UtC; 0.27 (0.05) ml‐min−1/mmHg × 10−2) decreased at the onset of exercise. Averaged over min 2–5 of exercise, the reduction in UtBF (n=6) was greater (P=0.02) at 13 m/min [−69 (21) %] vs. 7 m/min [−50 (11) %]. The UtC (n=5) response was also greater (P=0.03) at 13 m/min [−73 (19) %] vs. 7 m/min [−55 (7) %]. In response to short‐term treadmill exercise, rats exhibit a robust vasoconstrictor response in the uterine circulation which is sensitive to exercise intensity. Supported by MWU.

Risk Factors and Mediators of the Vascular Dysfunction Associated with Hypertension in Pregnancy

Normal pregnancy is associated with significant hemodynamic changes and vasodilation in the uterine and systemic circulation in order to meet the metabolic demands of the mother and developing fetus. Hypertension in pregnancy (HTN-Preg) and preeclampsia (PE) are major complications and life-threatening conditions to both the mother and fetus. PE is precipitated by various genetic, dietary and environmental factors. Although the initiating events of PE are unclear, inadequate invasion of cytotrophoblasts into the uterine artery is thought to reduce uteroplacental perfusion pressure and lead to placental ischemia/hypoxia. Placental hypoxia induces the release of biologically active factors such as growth factor inhibitors, anti-angiogenic proteins, inflammatory cytokines, reactive oxygen species, hypoxia-inducible factors, and antibodies to vascular angiotensin II receptor. These bioactive factors affect the production/activity of various vascular mediators in the endothelium, smooth muscle and extracellular matrix, leading to severe vasoconstriction and HTN. As an endothelial cell disorder, PE is associated with decreased vasodilator mediators such as nitric oxide, prostacyclin and hyperpolarizing factor and increased vasoconstrictor mediators such as endothelin, angiotensin II and thromboxane A(2). PE also involves enhanced mechanisms of vascular smooth muscle contraction including intracellular free Ca(2+) concentration ([Ca(2+)](i)), and [Ca(2+)](i) sensitization pathways such as protein kinase C, Rho-kinase and mitogen-activated protein kinase. Changes in extracellular matrix composition and matrix metalloproteases activity also promote vascular remodeling and further vasoconstriction in the uterine and systemic circulation. Characterization of the predisposing risk factors, the biologically active factors, and the vascular mediators associated with PE holds the promise for early detection, and should help design specific genetic and pharmacological tools for the management of the vascular dysfunction associated with HTN-Preg.

Circulating and Vascular Bioactive Factors During Hypertension in Pregnancy

Normal pregnancy is associated with significant vascular remodeling in the uterine and systemic circulation in order to meet the metabolic demands of the mother and developing fetus. The pregnancy-associated vascular changes are largely due to alterations in the amount/activity of vascular mediators released from the endothelium, vascular smooth muscle and extracellular matrix. The endothelium releases vasodilator substances such as nitric oxide, prostacyclin and hyperpolarizing factor as well as vasoconstrictor factors such as endothelin, angiotensin II and thromboxane A(2). Vascular smooth muscle contraction is mediated by intracellular free Ca(2+) concentration ([Ca(2+)](i)), and [Ca(2+)](i) sensitization pathways such as protein kinase C, Rho-kinase and mitogen-activated protein kinase. Extracellular matrix and vascular remodeling are regulated by matrix metalloproteases. Hypertension in pregnancy and preeclampsia are major complications and life threatening conditions to both the mother and fetus, precipitated by various genetic, dietary and environmental factors. The initiating mechanism of preeclampsia and hypertension in pregnancy is unclear; however, most studies have implicated inadequate invasion of cytotrophoblasts into the uterine artery, leading to reduction in the uteroplacental perfusion pressure and placental ischemia/hypoxia. This placental hypoxic state is thought to induce the release of several circulating bioactive factors such as growth factor inhibitors, anti-angiogenic proteins, inflammatory cytokines, reactive oxygen species, hypoxia-inducible factors, and vascular receptor antibodies. Increases in the plasma levels and vascular content of these factors during pregnancy could cause an imbalance in the vascular mediators released from the endothelium, smooth muscle and extracellular matrix, and lead to severe vasoconstriction and hypertension. This review will discuss the interactions between the various circulating bioactive factors and the vascular mediators released during hypertension in pregnancy, and provide an insight into the current and future approaches in the management of preeclampsia.

Placental nutrient supply and fetal growth

This review considers mechanisms by which transfer across the placenta takes place and how the capacity of the placenta to supply nutrients relates to fetal growth and vice versa. Blood flow through both uterine and umbilical circulations of the placenta, the structural properties of the placental exchange barrier and its related diffusional permeability, and the expression and activity of a wide range of transporter proteins in the syncytiotrophoblast, the transporting epithelium of the placenta, all need to be taken into account in considering placental supply capacity. We discuss the evidence that each of these factors affects, and is affected by, fetal growth rate and consider the regulatory mechanisms involved, with a particular focus on data that has emerged from study of the system A amino acid transporter. We consider that future work will build on the considerable foundation of knowledge regarding placental transfer mechanisms, as well as the other aspects of placental structure and function, to develop new diagnostic and therapeutic strategies for pregnancy complications, such as fetal growth restriction or overgrowth.

Plasma Adrenomedullin Levels during Multiple Pregnancy

Background: To estimate the normal level of adrenomedullin (AM) during multiple pregnancy. Methods: The study population consisted of 5 women with normal cycles, 130 women with normal pregnancy between 6 and 40 weeks of gestation, 93 women with twin pregnancy and 42 women with triplet pregnancy. Results: Total AM concentration in the first trimester (13.7 ± 0.58 fmol/ml), second trimester (26.8 ± 1.13 fmol/ml) and third trimester (37.8 ± 1.32 fmol/ml) in pregnant women was significantly higher than that in nonpregnant women (8.0 ± 0.71 fmol/ml). In each trimester, the maternal plasma concentrations of triplet-pregnant women were significantly higher than in twin and singleton-pregnant women. Umbilical venous AM levels (29.9 ± 2.63 fmol/ml) were higher than umbilical arterial AM (20.2 ± 2.04 fmol/ml). Conclusion: Since alterations in the AM concentration in maternal plasma may mediate compensatory vascular responses in the uterine circulation, it might be useful to know the normal level of AM during multiple pregnancy in order to detect abnormalities during multiple pregnancy.

Blood flow volume of uterine arteries in human pregnancies determined using 3D and bi-dimensional imaging, angio-Doppler, and fluid-dynamic modeling

The primary aim of this pilot study was to study uterine artery (UtA) blood flow volume in uneventful human pregnancies delivered at term, at mid and late gestation by means of 3D and bi-dimensional ultrasound imaging with angio-Doppler combined with fluid-dynamic modeling. Secondary aims were to correlate flow volume to placental site and to UtA Pulsatility Index (PI).Women with singleton, low-risk pregnancies were examined at mid and late gestation. The structure and course of the uterine artery (UtA) was studied in each patient by means of 3D-angio-Doppler and included vessel diameter D, blood flow velocity and PI (measured along the UtA). Fetal weight estimation and placental insertion site were assessed by ultrasound. A robust fluid-dynamic modeling was applied to calculate absolute flow and flow per unit fetal weight.Mean UtA diameter and blood flow velocity increased significantly (p < 0.0001) from mid-gestation to late gestation from 2.6 mm and 67.5 cm/s, to 3.0 mm and 85.3 cm/s, respectively, yielding an increasing absolute flow troughout gestation. h coefficient, derived by fluid-dynamic modeling to calculate mean velocity, increased significantly from 0.52 at mid-gestation to 0.57 at late gestation. UtA blood flow volume ml/min/kg-fetal weight was significantly higher at mid-gestation than at late gestation (535 ml/min/kg vs 193 ml/min/kg; p < 0.0001). In cases with strictly lateral placentas the ipsilateral UtA accommodates at mid and late gestation 63% and 67% of the total UtA flow. In central placentas UtA flow was evenly distributed between the two vessels. An inverse correlation was observed between PI and blood flow volume ml/min/kg (Pearson's coefficient r = −0.54).Our work confirms the technological and methodological limitations in the measurement of uterine artery blood flow. However, Doppler measurements supported by three-dimensional angio imaging of the uterine vessel, high resolution imaging and diameter measurement, and a robust mathematical model of local circulation adds a genuine new area of investigation into human uterine circulation during pregnancy.

Pregnancy Enhances Sustained Ca2+ Bursts and Endothelial Nitric Oxide Synthase Activation in Ovine Uterine Artery Endothelial Cells Through Increased Connexin 43 Function1

Endothelium-mediated vasodilation is specifically enhanced in uterine circulation during pregnancy, and production of nitric oxide (NO) is increased in response to a wide array of agonists. Uterine artery endothelial cells from nonpregnant (NP-UAECs) or pregnant (P-UAECs) ewes maintained in culture still show a pregnancy-enhanced difference in ATP-stimulated endothelial NO synthase (eNOS; official symbol NOS3) activation, even though NOS3 protein, purinergic receptors, and associated cell signaling proteins are expressed at equal levels. We have also shown that the pregnancy-enhanced endothelial cell NO response to ATP requires an enhanced and sustained capacitative entry phase that is likely mediated via canonical transient receptor potential protein/inositol 1,4,5-trisphosphate receptor type 2 interaction. In this study, we now show by simultaneous video imaging of individual Fura-2-loaded cells that the pregnancy-enhanced capacitative entry phase is not continuous and equal in all cells, but is in fact mediated as a series of periodic [Ca(2+)](i) bursts within individual cells. Not only does pregnancy increase the number of bursts over a longer time period in individual cells, but also a greater proportion of cells exhibit this burst activity, and at high cell density this occurs in a synchronous manner. The mediator of cell synchronization is connexin 43 (Cx43) gap junctions because 1) Cx43 is readily detectable by Western blot analysis in UAECs, whereas Cx40 and Cx37 are weakly detected or absent, and 2) pregnancy-specific enhancement of [Ca(2+)](i) bursts by ATP is blocked by inhibitory loop peptides selective to Cx43 ((43,37)GAP27) but not by a scrambled control peptide or (40)GAP27 or (40,37)GAP26 peptides, which are specific to Cx40 or Cx37. The relationship between Ca(2+) bursts and NOS3 activation is further established by the finding that (43,37)GAP27 inhibits ATP-stimulated NOS3 activation but has no effect on cell mitogenesis. We conclude that it is pregnancy-enhanced gap junction communication between cells that underlies pregnancy enhancement of capacitative entry via TRPC3 and, in turn, NOS3 activation. Such improved gap junction function allows greater and more sustained [Ca(2+)](i) responses to agents such as ATP within a single cell, as well as the additional recruitment of greater numbers of cells to the response in a coordinated and synchronous manner to support enhanced NO production.

OP14.06: Late-onset preeclampsia cannot be identified with either an anti-angiogenic profile in maternal plasma or uterine artery Doppler velocimetry

the subsequent development of abnormal uterine artery Doppler velocimetry (UTDV) in the second trimester (2T). Study design: This study is based on a cohort study design to examine the predictive value of PlGF, sEng and sVEGFR-1 plasma concentrations in the identification of patients destined to develop PE. Only patients that had samples obtained between 8–13 weeks and subsequently had UTDV between 20–25 weeks were included (n = 1,316). Results: 1) Women destined to have abnormal UTDV in the 2T had a lower median 1T plasma PlGF concentration than those with normal UTDV; 2) 1T plasma PlGF concentration of < 26.8 pg/ml (derived by ROC analysis) was associated with abnormalities in UTDV in the 2T (odd ratio 3.2; 95% CI 1.8–5.5) after adjusting for confounders; and 3). Women with abnormal UTDV, with and without subsequent PE, had a lower median 1T plasma PLGF concentration than those with normal UTDV and no PE. Conclusion: A low 1T plasma PlGF concentration is associated with increased impedance to flow in the uterine circulation in the 2T, regardless of whether or not the patient developed PE. These findings suggest that PlGF plays an important role in early placentation.

Vascular and Cellular Calcium in Normal and Hypertensive Pregnancy

Normal pregnancy is associated with significant hemodynamic changes in the cardiovascular system in order to meet the metabolic demands of mother and fetus. These changes include increased cardiac output, decreased vascular resistance, and vascular remodeling in the uterine and systemic circulation. Preeclampsia (PE) is a major complication of pregnancy characterized by proteinuria and hypertension. Several risk factors have been implicated in the pathogenesis of PE including genetic and dietary factors. Ca2+ is an essential dietary element and an important regulator of many cellular processes including vascular function. The importance of adequate dietary Ca2+ intake during pregnancy is supported by many studies. Pregnancy-associated changes in Ca2+ metabolism and plasma Ca2+ have been observed. During pregnancy, changes in intracellular free Ca2+ concentration ([Ca2+](i)) have been described in red blood cells, platelets and immune cells. Also, during pregnancy, an increase in [Ca2+](i) in endothelial cells (EC) stimulates the production of vasodilator substances such as nitric oxide and prostacyclin. Normal pregnancy is also associated with decreased vascular smooth muscle (VSM) [Ca2+](i) and possibly the Ca2+-sensitization pathways of VSM contraction including protein kinase C, Rho-kinase, and mitogen-activated protein kinase. Ca2+-dependent matrix metalloproteinases could also promote extracellular matrix degradation and vascular remodeling during pregnancy. Disruption in the balance between dietary, plasma and vascular cell Ca2+ may be responsible for some of the manifestation of PE including procoagulation, decreased vasodilation, and increased vasoconstriction and vascular resistance. The potential benefits of Ca2+ supplements during pregnancy, and the use of modulators of vascular Ca2+ to reduce the manifestations of PE in susceptible women remain an important area for experimental and clinical research.

Livedoid vasculopathy and pregnancy

Livedoid vasculopathy is a rare disease of unknown etiology that is characterized by recurrent painful ulceration of the feet, ankles, and legs. It leaves significant deep, white atrophic scars and was first described byMilian in 1929 [1]. Livedoid vasculopathy affects 1 person in 100 000 and is 3 times more common in young women than in young men [2], with one report stating that “during...pregnancy a markedly aggravated tendency was seen” [3]. A 27-year-old primigravida was referred by a dermatologist and attended a “high-risk” fetomaternal clinic atweek 11 of pregnancy. She had presented to the dermatologist at the age of 26 years, with a 1-year history of mottled eruptions over her legs, feet, and arms, which had become superficially ulcerated and painful. A skin biopsy showed thrombus,fibrinoid change of blood vessels, andfibrosis, togetherwith hyalinization of the vessel wall consistent with a diagnosis of livedoid vasculopathy. A full thrombophilia screen, coagulation screen, and immunologic profile were normal. In view of the association with vasculopathy, we were concerned about the potential risks of placental abruption, thrombosis, and fetal growth restriction. Treatment was started at 12 weeks with a daily dose of 75 mg of oral aspirin. Uterine artery Doppler studies showed no notching at 23 weeks. Serial growth scans were performed at weeks 28, 31, and 34, with fetal growth maintained along the 50th percentile. The lower-limb lesions worsened progressively, especially after 34 weeks. Focal areas of deep ulceration and necrosis developed, associated with increasing pain (Fig. 1). The patient received multidisciplinary team care, and labor was induced at 37 weeks and 4 days because of worsening symptoms, particularly severe pain. After cervical priming with two 3-mg prostaglandin pessaries, the patient had a normal delivery of a healthy girl weighing 3175 g (50th percentile birth weight for gestational age). Postnatally, there was rapid spontaneous improvement, especially of the leg lesions. In the present case, low-dose aspirin was prescribed to reduce the theoretic potential for adverse effects on the placental microcirculation. However, uterine artery Doppler at 23 weeks was normal, and subsequent growth scans showed no evidence of fetal growth restriction. It is unclear whether aspirin had a protective effect. Outside of pregnancy, low-molecular-weight heparin is restricted to patients for whom livedoid vasculopathy is refractory to treatment with platelet aggregation inhibitors [4]. Severe and widespread livedoid vasculopathy may show a good clinical response to intravenous methylprednisolone combined with pentoxifylline [3]. Other experimental treatments include intravenous immunoglobulin, hyperbaric oxygen, psoralen plus ultraviolet A, low-molecular-weight dextran, and rituximab. The use of these treatments during pregnancy has not been described. In this case, livedoid vasculopathy worsened throughout the pregnancy, especially in the third trimester, and was associated with significant pain. There was no evidence of compromise to uterine or fetal circulation. Most surprising was the rapid spontaneous improvement, particularly of the lower-limb lesions, after delivery. International Journal of Gynecology and Obstetrics 107 (2009) 248–257BRIEF COMMUNICATIONS

Gestagens in peripheral, uterine, ovarian and fetal blood in cows near term.

The aim of this study was to determine if bovine placenta is capable of producing the gestagen metabolites in vivo. The concentrations of 5 beta-pregnane-3 alpha-20 alpha-diol, 17 alpha,20 alpha-dihydroxyprogesterone and progesterone were measured by HPLC-RIA in samples obtained after surgical preparation from peripheral, uterine, fetal and ovarian blood of seven cows near term. Measurement of arterio-venous differences in maternal uterine and umbilical circulation confirmed the placental origin of 5 beta-pregnance-3 alpha,20 alpha-diol and 17 alpha,20 alpha-dihydroxyprogesterone, but not progesterone itself. 5 beta-pregnane-3 alpha,20 alpha-diol was preferentially secreted into the fetal compartment. The present experiment, according to earlier in-vitro studies, confirms that the preterm bovine placenta is qualified for in-vivo utilization and secretion of gestagen metabolites.

Nutritional regulation of uteroplacental prostaglandin production and metabolism in pregnant ewes and mares during late gestation.

Prostaglandins (PGs) are produced by a variety of uteroplacental tissues during pregnancy and are released into the fetal fluid sacs and both the uterine and umbilical circulations. Uterine PG output increases towards term and is enhanced by maternal undernutrition in pregnant ewes and mares. In both species, withdrawal of food but not water for 30-48 h increases uterine venous PG levels and the uterine venous arterial concentration differences in PGE and 13, 14, dihydro-15-keto-prostaglandin F2 alpha (PGFM), the stable metabolite of PGF2 alpha. The increments in uterine V-A concentration differences in PGE and PGFM increase towards term and are associated with raised plasma PG levels in the fetal circulation. The PG changes observed during fasting are closely related to the fall in plasma glucose and the rise in plasma FFA in peripheral plasma. When normal metabolite levels are restored either by refeeding or glucose infusion, there is a rapid fall in PG levels with a narrowing of the uterine V-A concentration differences in the ewe and mare. When the data from all the animals are combined, there is an inverse correlation between uterine glucose uptake and PGFM output in both the pregnant ewe and mare. The availability of glucose and FFA to the gravid uterus therefore has an important role in controlling uteroplacental PG production and metabolism in late gestation although the specific steps in biochemical pathways regulated by these metabolites remain unclear. In the ewe, fasting increases uterine contractility and leads to early delivery of viable lambs in animals close to term (> 95% gestation), whereas in the mare it causes premature delivery of non-viable foals in most animals in late gestation (> 80% gestation). Nutritionally induced changes in uteroplacental PG production and metabolism therefore have important consequences for the outcome of pregnancy and may have a pivotal role in the induction of labour both before and at normal term.

Inhibition of Nitric Oxide Synthases Abrogates Pregnancy-Induced Uterine Vascular Expansive Remodeling

Background/Aims: It was the aim of this study to test the hypothesis that hypertension and/or inhibition of nitric oxide (NO) synthases alters uterine vascular remodeling during pregnancy. Methods: Using a model of hypertension (NO synthase inhibition with L-NAME) in nonpregnant and pregnant rats, comparisons were made with age-matched controls, as well as with animals receiving hydralazine along with L-NAME to maintain normotension in the presence of NO synthase inhibition. Circumferential and axial remodeling of large (main uterine, MUA) and small (premyometrial radial) arteries were quantified and compared. Results:L-NAME treatment prevented expansive circumferential remodeling of the MUA; cotreatment with hydralazine was without effect. Circumferential remodeling of smaller premyometrial radial arteries was also significantly attenuated in hypertensive pregnant animals, while premyometrial radial arteries from rats receiving hydralazine with L-NAME were of intermediate diameter. Neither hypertension nor NO synthase inhibition had any effect on the substantial (200–300%) axial growth of MUA or premyometrial radial arteries. Conclusion: NO plays a major role in facilitating pregnancy-induced expansive remodeling in the uterine circulation, particularly in larger arteries. Some beneficial effects of hydralazine on expansive circumferential remodeling were noted in smaller radial vessels, and these may be linked to its prevention of systemic hypertension and/or to local effects on the arterial wall. Neither NO synthase inhibition nor hypertension had any effect on arterial longitudinal growth.

Maternal Uterine Vascular Remodeling During Pregnancy

Sufficient uteroplacental blood flow is essential for normal pregnancy outcome and is accomplished by the coordinated growth and remodeling of the entire uterine circulation, as well as the creation of a new fetal vascular organ: the placenta. The process of remodeling involves a number of cellular processes, including hyperplasia and hypertrophy, rearrangement of existing elements, and changes in extracellular matrix. In this review, we provide information on uterine blood flow increases during pregnancy, the influence of placentation type on the distribution of uterine vascular resistance, consideration of the patterns, nature, and extent of maternal uterine vascular remodeling during pregnancy, and what is known about the underlying cellular mechanisms.

Fetal Asphyxia Leads to a Decrease in Dorsal Raphe Serotonergic Neurons

The aim of the present study was to determine the effects of fetal asphyxia (FA) on anxiety and serotonergic neurons in young adult and middle-aged rats. FA was induced at embryonic day 17 by clamping the uterine circulation for 75 min. Anxiety-related behavior was tested in an open field, and design-based stereology was used for counting serotonergic (5-hydroxytryptamine/serotonin, 5-HT) neurons in the dorsal raphe nucleus (DRN). The open field revealed increased anxiety in the 19-month-old FA rats in comparison to control animals. No significant differences were found in DRN 5-HT neuron numbers at 6 months. At 19 months, however, FA significantly lowered the mean density and volume of 5-HT neurons in the DRN as compared to controls. Further, an age-related reduction was found in the total number, the mean density and the mean volume of 5-HT neurons within the FA group. In conclusion, FA is associated with increased anxiety and age-related changes in 5-HT immunohistochemistry within the DRN. These results support the notion that insults caused by asphyxiation during critical periods of brain development could create a predisposition to serotonergic abnormalities and anxiety deficits in adulthood.

Is It More Informative to Focus on Cardiac Output than Blood Pressure during Spinal Anesthesia for Cesarean Delivery in Women with Severe Preeclampsia?

Is It More Informative to Focus on Cardiac Output than Blood Pressure during Spinal Anesthesia for Cesarean Delivery in Women with Severe Preeclampsia?

Doppler ultrasound of uterine and fetoplacental circulation: placental laterality, normal values and reference curves

Doppler ultrasound assessment of blood flow velocity waveforms from the maternal and fetal sides of the placenta in normal pregnancies, taking into consideration placental location, in order to establish normal values and reference curves. A cross sectional study of uneventful singleton pregnancies with gestational ages from 18 to 41 weeks and later on healthy newborns was performed by continuous-wave-Doppler ultrasound. Doppler flow signals from the uterine artery or the corresponding ascending branch and the umbilical arteries were analysed using the resistance index RI. The RI-values from the uterine circulation were classified according to the proximity of the placenta. Normal values and reference curves were established on the basis of centiles. After consideration of exclusion criteria, 757 pregnancies remained for evaluation. The resistance index reference curves of the uterine circulation were dependent on placental location, with proximal RI-values being lower, but with nearly constant course during the second half of pregnancy. In contrast, the umbilical artery RI-values were higher but showed a continuous decrease. In the second half of pregnancy, down stream flow resistance of the uterine circulation is very low and nearly constant but depends on placental location. The fetoplacental circulation shows high flow resistances which decrease with increasing gestational age. These reference curves are comparable with others where placental location is taken into consideration.

The Assessment of Unilateral Uterine Artery Ligation in Radical Abdominal Trachelectomy with Three-Dimensional Power Doppler Ultrasonography

The conservation of uterine arteries during radical trachelectomy has led to considerable debate among gynecologic oncologists. Some authors have reported successful case studies of the ligation of bilateral uterine arteries, but other authors remain unconvinced of the artery ligation procedure. We report a case that employed three-dimensional power Doppler ultrasonography (3D-PDUS) to assess the microvascular pattern of uterine blood circulation after the ligation of a unilateral uterine artery during radical abdominal trachelectomy. The assessment of the uterine vascular circulation via the 3D-PDUS revealed no significant differences in the vascular blood supply of bilateral uterine arteries 4 months postoperatively. [International Journal of Gerontology 2008; 2(1): 22–25]