Reduction In Uterine Blood Flow Research Articles

Gestational Long Term High-Altitude Hypoxia and Metabolomic Reprogramming in Uterine Arteries of Adult Sheep

Long term hypoxic stress during pregnancy causes a reduction in uterine blood flow, compromising oxygen and nutrient delivery to the fetus. There are multiple epigenetic factors involved in the structural and functional impairments that underlie the impairments in uterine arterial function. Evidence indicates that oxidative stress plays an important role to the decrements in blood flow following high altitude pregnancy. The purpose of the current study was to test the hypothesis that changes in oxylipin and endocannabinoid signaling are important to the increases in oxidative stress along with changes in glucose and fat metabolism. To further understand the mechanisms associated with disruption of uterine artery blood flow due to high altitude pregnancy, we examined a high altitude pregnant sheep model. Pregnant and non-pregnant sheep were housed either at low (700m) or high altitude (3801 meters) for 110+ days of pregnancy. Uterine arteries were excised from pregnant and non-pregnant sheep and targeted as well as untargeted metabolomic analyses were performed to test the hypothesis that hypoxia increases oxidative stress and reduces oxidative metabolism. Enrichment analysis of the metabolites show that hypoxia impacted several key biochemical pathways. At high altitude there were decreases in Alpha Linolenic Acid and Linoleic Acid Metabolism along with reductions in Pyruvate Metabolism and antioxidants. Further to this, there was an increase in the metabolism of Arachidonic Acid, Glycerolipids, and Methionine, which are linked to inflammation, cell signaling, and cell growth. Fully understanding how increased oxidative stress and inflammatory pathways along with decreased antioxidant capacity and changes in cellular metabolism is tied to malformations in uterine arterial structure and function following high altitude gestation is an active area of investigation. This work was supported by the National Institutes of Health Grants NIH R01HL155295, R01HL149608, R03HD098477, P01HD083132, and U24DK097154. Additional support was provided by the Loma Linda University School of Medicine and West Coast Metabolomics Center. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

9 Randel Lecture: In Vivo investigation of pregnancy Physiology

Abstract Pregnancy in any mammal requires the integration of three distinct compartments; the maternal, placental and fetal compartments. Compromised function of any of the three compartments can result in suboptimal pregnancy outcomes, including increased morbidity and mortality at delivery, reduced livestock production efficiency and adult-onset of metabolically-related disease in humans. To accurately understand the progression of both normal and compromised pregnancies, therefore, requires the simultaneous assessment of all three compartments, which for most species is not technically feasible. Consequently, over the past 60 yr the pregnant sheep has been used extensively for in vivo investigation of pregnancy physiology. The ability to place indwelling catheters, within both maternal and fetal vessels, allows the simultaneous steady-state assessment of uterine and umbilical blood flows, hormone secretion, and nutrient uptake and utilization of nutrients by each of the three compartments, under non-stressed and non-anesthetized conditions. This has provided unrivalled insight into the physiology of pregnancy, and the realization that the placenta is a highly metabolic tissue, utilizing the majority of oxygen and glucose taken up by the uterus. However, the deficit in studying pregnant sheep is the lack of genetic models, readily available in rodents, that could help define specific gene function during pregnancy. Consequently, we developed in vivo lentiviral-mediated RNA interference (RNAi) methods to specifically alter the abundance of specific gene transcripts/proteins within the placenta, beginning at 9 d of gestation (dGA). Our lentiviral-mediated approach limits the RNAi to the trophectoderm derivatives of the placenta. Initially we used this approach to determine the importance of PRR15 and LIN28 during the establishment of pregnancies, but turned our efforts towards combining in vivo RNAi with steady-state physiological assessments during late gestation to examine the function of genes involved in placental nutrient transport (SLC2A3) and placenta derived hormones (CSH). By creating a placental deficiency in SLC2A3, not only was the fetus smaller and hypoglycemic at mid-gestation, but by interfering with placental glucose uptake, maternal hormone concentrations were also impacted, yet near-term, a distinctly different phenotype was present. For the placental hormone CSH (a.k.a. placental lactogen), CSH RNAi not only impacts placental and fetal growth, but also reductions in uterine blood flow, nutrient fluxes to the fetus, and produces an altered hormonal environment. Combining these methodological approaches provides new and often unexpected insights into the physiological integration of the maternal, placental and fetal compartments. Supported by NIH-NICHD grants HD093701 and HD094952.

33 Identification of How Future Climates May Impact the Reproductive Herd and What This May Mean for Nutrition

Abstract Changes in our climate with global warming will translate to an expansion in the seasons and an increased incidence of extreme heat events, such that heat stress (HS) will become a major management issue. This poses particular challenges to the reproductive herd, as by virtue of their increased physical size and pregnancy, they are less resilient to environmental challenges. Recent work from our laboratory has quantified the performance of summer mated piglets on productivity, demonstrating that these litters are lighter at birth, have a lighter placenta weight and are more likely to be stillborn. These piglets also take longer to reach market weight and have increased carcass backfat, which can trigger market penalties. Collectively our studies demonstrate that summer conditions result in developmental abnormalities in piglets, potentially through placental insufficiency. Additionally, HS was challenging sows during the periparturient period, resulting in more stillbirths. Two subsequent climate-controlled studies quantified the effects of HS (cyclic 28 to 33 oC) during early to mid-pregnancy (d 40 to 60), when the placenta is undergoing rapid growth, as well as the effects of HS (cyclic 28 to 30 oC) in the periparturient period (d 110 of pregnancy to farrowing). In the first study, gestational HS did not influence the number or size of the piglets at mid-gestation but increased placental mass by 22% and reduced Longissimus muscle fiber hyperplasia by 16%. The apparent enlargement of the placenta at mid-gestation may reflect an adaptation to a reduction in uterine blood flow. In other species, HS is known to reduce blood flow to the splanchnic bed and reproductive tract organs, as blood is redistributed to the periphery and upper respiratory tract to augment heat dissipation. Therefore, the prioritization of placental growth by the piglet may represent an adaptation against a backdrop of insufficient nutrient supply. Whilst reductions in muscle fiber hyperplasia were associated with reduced vascularity, although it is not clear if this was a cause or effect. In the second study, the effects of periparturient HS resulted in a 30% increase in stillbirths, with surviving piglets having lower umbilical vein blood oxygen saturation and increased meconium staining. This supports the likelihood of HS restricting uterine and umbilical blood flows, resulting in increased periparturient fetal stress. Collectively these studies emphasize the challenges that climate change poses to swine production and that addressing these challenges will require a whole farm approach. In the near term, it is likely that advances in nutrition will form an important component in adjusting to a changing climate and minimize production losses.

Impact of reduced uterine perfusion pressure model of preeclampsia on metabolism of placenta, maternal and fetal hearts

Preeclampsia is a cardiovascular pregnancy complication characterised by new onset hypertension and organ damage or intrauterine growth restriction. It is one of the leading causes of maternal and fetal mortality in pregnancy globally. Short of pre-term delivery of the fetus and placenta, treatment options are limited. Consequently, preeclampsia leads to increased cardiovascular disease risk in both mothers and offspring later in life. Here we aim to examine the impact of the reduced uterine perfusion pressure (RUPP) rat model of preeclampsia on the maternal cardiovascular system, placental and fetal heart metabolism. The surgical RUPP model was induced in pregnant rats by applying silver clips around the aorta and uterine arteries on gestational day 14, resulting in ~ 40% uterine blood flow reduction. The experiment was terminated on gestational day 19 and metabolomic profile of placentae, maternal and fetal hearts analysed using high-resolution 1H NMR spectroscopy. Impairment of uterine perfusion in RUPP rats caused placental and cardiac hypoxia and a series of metabolic adaptations: altered energetics, carbohydrate, lipid and amino acid metabolism of placentae and maternal hearts. Comparatively, the fetal metabolic phenotype was mildly affected. Nevertheless, long-term effects of these changes in both mothers and the offspring should be investigated further in the future.

Uterine torsion and intrauterine growth restriction: Case report and systematic literature review

Uterine torsion (UT) in pregnancy is a rare condition in obstetric practice. It is defined as a rotation of the uterus of more than 45° around its long axis. Presentations are varied and, most of the time, this condition is recognized at laparotomy or cesarean section (CS). The aim of this study is to summarize the latest evidence about UT in pregnancy. A systematic research of the literature was conducted fetching all papers published from March 2006 to June 2020. We collected data regarding clinical features, treatment, and feto-maternal outcomes. Finally, we reported data of a case of UT associated with intrauterine growth restriction (IUGR) diagnosed and treated at our institution. According to our search strategy, 38 articles were included. In 66% of the cases, acute symptomatology was present at the onset, most frequently abdominal pain was reported. In one-third of the cases, UT was diagnosed during CS without clinical suspicion. Only in two cases, including our case, IUGR was reported. Most (66%) of the cases presented a 180° torsion. In the majority of the cases, a CS was performed also with a deliberate or accidental posterior hysterotomy. One and six cases of maternal and fetal death were, respectively, reported. UT is an infrequent obstetric condition but should be considered in case of abdominal pain, vomiting, or shock presentation during pregnancy. It could lead to a reduction in uterine blood flow contributing to poor placental perfusion, even though more evidence is needed to clarify this link.

Effects of the ovary and conceptus on uterine blood flow in the pig

Summary. Changes in uterine blood flow throughout pregnancy appear to be due to steroid-induced alterations in uterine arterial tone and contractility. Arterial contractility is a transient reduction in luminal diameter in response to nerve stimulation or to an alpha-1 adrenergic agonist, leading to short-term reduction in uterine blood flow. Tone is the pressure exerted by an arterial segment against an intraluminal flow (distensibility) and is considered to set the baseline rate of flow. These phenomena appear to be regulated individually, with tone changes predominating during pregnancy. In pregnancy, tone is markedly depressed as oestrogen concentrations rise, and the vessel is distended and flaccid. Arterial tone is a function of the amount of calcium available to the contractile proteins of the arterial smooth muscle, which is derived from extracellular sources. Calcium availability is regulated by the opening and closing of calcium channels in the surface membrane in response to changes in the membrane potential. The loss of uterine arterial tone associated with oestrogen results from a markedly depressed uptake of calcium by the vessels. A significant negative correlation (P < 0.001; r = – 0.93) is observed between uterine arterial uptake of calcium and the concentrations of oestrogens in systemic blood of pigs throughout gestation. Several lines of evidence suggest that the blockade of potential-sensitive calcium channels associated with uterine hyperaemia is produced by catechol oestrogens, short-lived metabolites of oestrogens that are found in the circulation when oestrogen levels are high. Synthesis of catechol oestrogens from the parent oestrogens has been shown to occur in the placenta, endometrium and uterine arteries of pigs. In addition, perfusion of uterine arteries from nonpregnant pigs with catechol oestrogens, but not free oestrogens, in vitro significantly reduces both the tone and the uptake of calcium by the vessels. Contractility of the arteries to nerve stimulation or phenylephrine, however, is not affected. These data suggest that the pig conceptus, through production of catechol oestrogens, locally increases arterial distensibility, resulting in increased baseline flow to each fetal—placental unit. The contractility (reactivity) of the uterine arterial vasculature to adrenergic agonists or other vasoactive agents, however, is not affected. In this way, the conceptus can maintain the locally elevated flows necessary for its survival while the maternal system can continue to respond to life-threatening stimuli by transiently rerouting blood flow away from the uterus and towards other vascular beds more necessary for maternal survival.

B-mode and Doppler Ultrasonographic Assessment of Uterine Involution in Ewes Treated with Two Different Doses of ProstaglandinF2α

Background: Several studies consisted of postmortem evaluations and B-mode ultrasonography have been performed on ovine uterine involution. However, researches with Doppler ultrasonography are very limited in ewes. Doppler ultrasonography is a non-invasive method which provides information about vascular dynamics of the tissues which cannot be examined by B-mode ultrasonography. The aim of the study was to evaluate the effects of two different PGF2α doses on uterine measurements by real time B-mode ultrasonography; and on uterine artery hemodynamics by pulsed-wave Doppler analysis during postpartum uterine involution in ewes.Materials, Methods &amp; Results: The study was conducted with 30 primiparous Kiwircik ewes which lambed singleton without any complication. The ewes were randomly divided into three groups (n= 10 for each group). A single i.m. injection of 125 μg/sheep PGF2α, 75 μg/sheep PGF2α, and 1.0 mL/sheep sterile saline solution were administered to Group 1, 2, and 3, respectively. The day of parturition was considered as the first day of the study. Examinations were performed on days 1, 2, 3, 7, 14, 21 and 28. Diameters of previously gravid horn and caruncles were measured by real time B-mod ultrasonography. Presence of lochia was also noted. Uterine artery pulsatility index (PI), resistance index (RI), systolic/diastolic ratio (S/D) values were measured by pulsed-wave Doppler ultrasonography. The one-way analysis of variance and Duncan’s test were used for statistical analysis. The mean previously gravid horn diameters of ewes were 8.30 ± 0.16 cm and 1.53 ± 0.07 cm on day 1 and day 28, respectively. Previously gravid horn and caruncle diameters had a similar declining pattern in all groups as involution period proceeded. Involution was mostly completed by day 21. More than 50% reduction in uterine size was achieved in prostaglandin administered groups by day 7. Caruncles were not able to be identified after the second week postpartum. Lochia was observed for a longer period in control group. Uterine artery PI and RI showed fluctuations throughout involution period with a similar pattern among groups. S/D values progressively increased until day 14, then showed a decreasing pattern.Discussion: The effects of different PGF2α doses on uterine measurements and uterine artery hemodynamics during postpartum period were compared in ewes for the first time. The uterine size reduction in prostaglandin administered groups suggested that both PGF2α doses were effective in uterine involution. The last observation of lochia in uterine cavity were achieved by day 7 in prostaglandin administered groups, suggesting both PGF2α doses trigger uterine contractions which lead to the removal of uterine content. Automatic measurements by Doppler device were taken in order to provide uniformity and to prevent operator-based bias. The significantly higher uterine artery PI value found in Group 1 on day 1 might suggest the stimulatory effect of PGF2α administration on uterine contractility synergitically with already released endogenous PGF2α. Uterine artery PI and RI showed fluctuations throughout involution period and reached their peak values on day 14. The increasing S/D values up to day 14 indicated increasing diastolic flow, increasing resistance and decreasing blood perfusion in prostaglandin administered groups. Prostaglandin administered groups tended to show higher hemodynamic parameters throughout the study which suggested a vasoconstrictor effect of PGF2α. In conclusion, PGF2α administration on the day of parturition might have constrictor effects both on uterine artery and myometrium which leads to a reduction in uterine blood flow and a rapid decline in uterine size especially during early puerperium even with a reduced dose.

Комплексная оценка периоперационного периода при эмболизации маточных артерий на основе анализа маркеров стресс-реакции и допплерометрического контроля редукции маточного кровотока

Комплексная оценка периоперационного периода при эмболизации маточных артерий на основе анализа маркеров стресс-реакции и допплерометрического контроля редукции маточного кровотока

Inhaled nicotine equivalent to cigarette smoking disrupts systemic and uterine hemodynamics and induces cardiac arrhythmia in pregnant rats

Maternal smoking with obligatory nicotine inhalation is associated with preterm delivery, low birth weight, fetal growth retardation and developmental defects. We tested the hypothesis that cigarette smoking-relevant nicotine inhalation during pregnancy impairs cardiovascular function and uterine hemodynamics with consequential fetal ischemia. Pregnant rats exposed to episodic inhaled nicotine via a novel lung alveolar region-targeted aerosol method produced nicotine pharmacokinetics resembling cigarette smoking in humans. This clinically relevant nicotine aerosol inhalation (NAI) induced transient reduction and irregular fluctuations in uterine artery blood flow associated with cardiac arrhythmia and high magnitude irregular fluctuations of systemic blood pressure. The arrhythmia included sinoatrial (SA) block, sinus arrest, 2° and 3° atrioventricular (A-V) block and supraventricular escape rhythm. These effects were blocked by the nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine. Resection of the ovarian nerve, which innervates uterine blood vessels, counteracted the NAI-induced reduction in uterine blood flow. We suggest that the rapid rise pattern of arterial blood nicotine concentration stimulates and then desensitizes autonomic nAChRs leading to disruptions of cardiac function as well as systemic and uterine hemodynamics that reduces uteroplacental blood flow, a mechanism underlying maternal smoking-associated pregnancy complications and developmental disorders. These findings challenge the safety of pure nicotine inhalation, i.e., E-cigarettes.

MPS 13-06 APPLICATION OF NOVEL REDUCED UTERINE PERFUSION PRESSURE (RUPP) MODEL OF PREECLAMPSIA IN C57BL/6J MICE

Objective: Preeclampsia (PE) is a pregnancy-induced hypertension with proteinuria that typically develops after 20 weeks of gestation. A reduction in uterine blood flow causes placental ischemia and placental release of anti-angiogenic factors such as soluble fms-like tyrosine kinase (sFlt-1) followed by PE. Although the reduced uterine perfusion pressure (RUPP) model is widely used in rats, investigating the genetics of PE has been problematic because it has been difficult to make a useful RUPP model in mice. We established novel RUPP model of PE in outbred ICR-strain. The aim of the present study is to develop RUPP model ofC57BL/6J (B6)-strain mice, widely used strain in genetically engineered mice. Design and Method: We bilaterally ligated ovarian vessels distal to ovarian branches, uterine vessels, or both in B6-strain mice at 14.5 days post coitum (dpc). BP, renal phenotype and pregnancy outcome were analyzed. Results: Unlike the RUPP models in ICR-strain mice, ligation of ovarian vessels distal to ovarian branches, uterine vessels without space caused miscarriage in B6-strain mice. We next tied uterine vessels with nylon thread, followed by removal of the thread to provide a small space. This caused significant fetal growth restriction. Conclusions: Pregnancy outcome caused by RUPP in mice was different depending on mouse strains. This model is expected to be useful for investigating pathogenesis of PE in genetically engineered mice and for evaluating new therapies for PE.

OS 21-08 NOVEL REDUCED UTERINE PERFUSION PRESSURE (RUPP) MODEL OF PREECLAMPSIA IN MICE

Objective: Preeclampsia (PE) is a pregnancy-induced hypertension with proteinuria that typically develops after 20 weeks of gestation. A reduction in uterine blood flow causes placental ischemia and placental release of anti-angiogenic factors such as soluble fms-like tyrosine kinase (sFlt-1) followed by PE. Although the reduced uterine perfusion pressure (RUPP) model is widely used in rats, investigating the genetics of PE has been problematic because it has been difficult to make a useful RUPP model in mice. The aim of the present study is to establish a novel PE model using an improved RUPP method in mice. Design and Method: As shown in the Figure 1B, we bilaterally ligated ovarian vessels distal to ovarian branches, uterine vessels, or both in ICR-strain mice at 14.5 days post coitum (dpc). BP, renal phenotype and pregnancy outcome were analyzed. Results: Unlike the RUPP models described in the literature, this model did not constrict the abdominal aorta, which allowed BP to be measured with a tail cuff. RUPP in mice had elevated BP, increased urinary albumin excretion, severe endotheliosis, and mesangial expansion. They also had an increased incidence of miscarriage and premature delivery. Embryonic weight at 18.5 dpc was significantly lower than that in sham mice. The closer to the ligation site the embryos were, the higher the resorption rate and the lower the embryonic weight. The phenotype was more severe in the order of ligation at the ovarian vessels < uterine vessels < both. Conclusions: We developed a novel RUPP mouse model that recapitulates the phenotype of PE. This model is expected to be useful for investigating pathogenesis of PE in genetically engineered mice and for evaluating new therapies for PE.

67 Application of a novel RUPP model to C57BL/6J mice

Introduction Reduction of uterine blood flow is useful for studying pathogenesis of preeclampsia (PE). Although reduced uterine perfusion pressure (RUPP) is widely used as a model of PE in rats, investigating the genetics of PE has been slow because it has been difficult to make a useful RUPP model in mice. Moreover, rat model of RUPP does not allow one to measure BP using tail cuffs. We established a novel RUPP model of PE in outbred ICR mice, which allows one to evaluate BP using tail cuff (Fushima et al. PLOS ONE, 2016). Objectives The aim of the present study is to develop RUPP model of C57BL/6J (B6) mice, a widely used strain in genetically engineered mice. Methods We bilaterally ligated ovarian vessels distal to ovarian branches, uterine vessels, or both in B6 mice at 14.5 dpc. BP, renal phenotype and pregnancy outcome were analyzed. Results Unlike the RUPP model in ICR mice, ligation of ovarian vessels or uterine vessels caused miscarriages in B6 mice. We next tied uterine vessels with a nylon thread, followed by removal of the thread to provide a small space for a little blood flow. This caused significant fetal growth restriction. Different from ICR mice BP changes were insignificant. Conclusions Pregnancy outcome caused by RUPP is different depending on the strains of mice. This RUPP model is expected to be useful for investigating pathogenesis of PE and FGR in genetically engineered mice and for evaluating new therapies for these conditions.

Reduced Uterine Perfusion Pressure (RUPP) Model of Preeclampsia in Mice

Preeclampsia (PE) is a pregnancy-induced hypertension with proteinuria that typically develops after 20 weeks of gestation. A reduction in uterine blood flow causes placental ischemia and placental release of anti-angiogenic factors such as sFlt-1 followed by PE. Although the reduced uterine perfusion pressure (RUPP) model is widely used in rats, investigating the role of genes on PE using genetically engineered animals has been problematic because it has been difficult to make a useful RUPP model in mice. To establish a RUPP model of PE in mice, we bilaterally ligated ovarian vessels distal to ovarian branches, uterine vessels, or both in ICR-strain mice at 14.5 days post coitum (dpc). Consequently, these mice had elevated BP, increased urinary albumin excretion, severe endotheliosis, and mesangial expansion. They also had an increased incidence of miscarriage and premature delivery. Embryonic weight at 18.5 dpc was significantly lower than that in sham mice. The closer to the ligation site the embryos were, the higher the resorption rate and the lower the embryonic weight. The phenotype was more severe in the order of ligation at the ovarian vessels < uterine vessels < both. Unlike the RUPP models described in the literature, this model did not constrict the abdominal aorta, which allowed BP to be measured with a tail cuff. This novel RUPP model in mice should be useful for investigating the pathogenesis of PE in genetically engineered mice and for evaluating new therapies for PE.

A mathematical model to simulate the cardiotocogram during labor. Part A: Model setup and simulation of late decelerations

The cardiotocogram (CTG) is commonly used to monitor fetal well-being during labor and delivery. It shows the input (uterine contractions) and output (fetal heart rate, FHR) of a complex chain of events including hemodynamics, oxygenation and regulation. Previously we developed a mathematical model to obtain better understanding of the relation between CTG signals and vital, but clinically unavailable signals such as fetal blood pressure and oxygenation.The aim of this study is to improve this model by reducing complexity of submodels where parameter estimation is complicated (e.g. regulation) or where less detailed model output is sufficient (e.g. cardiac function), and by using a more realistic physical basis for the description of other submodels (e.g. vessel compression).Evaluation of the new model is performed by simulating the effect of uterine contractions on FHR as initiated by reduction of uterine blood flow, mediated by changes in oxygen and blood pressure, and effected by the chemoreflex and baroreflex. Furthermore the ability of the model to simulate uterine artery occlusion experiments in sheep is investigated.With the new model a more realistic FHR decrease is obtained during contraction-induced reduction of uterine blood flow, while the reduced complexity and improved physical basis facilitate interpretation of model results and thereby make the model more suitable for use as a research and educational tool.

30(+) years of exercise in pregnancy.

In 1980 I came to Loma Linda to study maternal exercise, with Dr. Longo as my mentor. For millennia strenuous exercise was considered harmful for the fetus. Early studies reinforced that idea, by showing that exercise reduced uterine blood flow and fetal PO2 by up to 40 and 29 %, respectively. But utero-placental reserve is ~50 %. So why was fetal PO2 so much reduced during exercise?Methods proved to be important. It took chronically instrumented animals accustomed to the laboratory environment, experiments standardized to fitness of the individual (%VO2max), measurement of total uterine blood flow, and blood gas values corrected for body temperature. The results were simple and hold till this day. Uterine blood flow decreases linearly with maternal heart rate increase, which depends on exercise intensity and duration. Maximal reduction in uterine blood flow is ~20 % and uterine O2-uptake remains unaltered because blood flow reduction is compensated by increases in hematocrit and uterine O2-extraction. Fetal body temperature increases with that of the mother by ~2 °C at maximal exercise and fetal blood gas values are little affected by exhaustive maternal exercise, if properly corrected for temperature. So I left Loma Linda knowing that pregnant sheep can exercise to exhaustion without harm to the fetus, thanks to effective compensatory mechanisms.After returning to Erasmus University Rotterdam further studies in humans showed that physical fitness is unaffected by pregnancy, weight-gain affects performance, and strenuous exercise in healthy pregnant women does not harm the fetus. Thus, the millennia-old perspective has changed.

Isolated small uterine arteries from non-pregnant and term pregnant rats exhibit regulatory responses to elevations in extravascular pressure

An adequate blood supply is essential for the maintenance of uterine function and fetal health during parturition. However, labouring uterine contractions will impart compressive forces on small uterine arteries (SUA). We demonstrate that isolated, pressurised rat SUA arteries, pre-constricted with arginine vasopressin or high potassium solution, exhibit regulatory responses to elevations in extravascular pressure (EVP) which maintain internal diameter constant at EVPs of 0–40 mm Hg. This response is endothelium independent and is not modulated by pregnancy. No regulation was observed in calcium free solution. SUA myogenic responses to elevated EVP likely represents a mechanism for limiting reductions in uterine blood flow during uterine contraction.

Bone growth and sexual dimorphism at birth in intrauterine-growth-retarded rats

This paper addresses the effect of a reduction of uterine blood flow (RUB) on postcranial bone growth in rats. The objectives were: (1) to discover and characterize the changes evoked by growth retardation through a reduction in placental blood flow, (2) to see if the resulting growth retardation is different in each bone, and (3) to analyze any sex-specific features. RUB was induced by the partial bending of uterine vessels at day 1 of pregnancy. Control and sham-operated animals were also included. The animals were X-rayed at birth. The lengths and widths of the humerus, radius, and femur and pelvic length, interischial, interpubic, and pubic widths were measured. Data were analyzed by ANOVA and LSD post hoc tests. The intersubject analysis showed significant differences between groups and non-significant differences between sexes. In males, sham-operated and RUB showed significant differences in pelvic lengths and widths, and humeral, radial, femoral, and tibial widths. In females, there were significant differences only for humeral widths, radial lengths and widths, and femoral and tibial widths. We conclude that reduced blood flow delays appendicular bone growth as observed at birth. Pelvic length was more affected than that of the limbs. The widths of the pelvic and limbs bones, in turn, were more altered than the lengths, and the growth of the males more than that of the females. Partial bending of uterine vessels compromised postcranial growth, though under such disadvantageous circumstances the females proved to be more capable of growing and thus more resilient than the males.

Oxygen uptake of the human fetus at term

To measure oxygen uptake of term human fetuses and compare the values between those delivered vaginally following normal labor and those delivered by cesarean section before the onset of labor. This was a prospective cross-sectional study. University teaching hospital. Twenty healthy pregnant women at term (38-42 weeks) were included in this study. Among them, 10 were delivered by elective cesarean section and 10 had normal vaginal delivery. Umbilical vein volume blood flow was measured <24 hours before delivery. Immediately after delivery, the fetal weight was determined, and the umbilical venous and arterial blood samples were obtained. Blood gas analysis was performed and hemoglobin content was measured. Fetal oxygen uptake was calculated as a product of umbilical venous blood flow and the difference in the umbilical arterial and venous oxygen content. We found that the mean oxygen uptake in human fetuses at term (median gestational age 39 weeks) to be 6.58 ml/min/kg (i.e. 0.29 mmol/min/kg). There was no significant difference in oxygen uptake between fetuses delivered following uncomplicated normal labor and those delivered by elective cesarean section before the onset of labor. Oxygen uptake of the appropriately grown normal human fetus at term is approximately 6.6 ml/kg/min and is not significantly affected by normal labor and delivery. Human fetuses tolerate intermittent reductions in uterine blood flow and oxygen supply associated with myometrial contractions during normal labor quite well.

Programming of hypertension: the nervous kidney

two decades after Barker and coworkers ([2][1]) described an inverse epidemiological relationship between birth weight and risk of adult cardiovascular morbidity, including hypertension, the pathophysiology of prenatally programmed hypertension remains incompletely understood. Experimental models

Vasopressors in obstetrics: what should we be using?

Historically, ephedrine has been recommended as the best vasopressor in obstetrics because animal studies showed it caused less reduction in uterine blood flow compared with alpha-agonists. Recent clinical evidence, however, suggests that this is not as important as initially thought. This review evaluates current data with a focus on spinal anesthesia for cesarean section. Ephedrine and phenylephrine have been most investigated. Advantages of ephedrine include familiarity, long history and low propensity for uteroplacental vasoconstriction. Ephedrine, however, has limited efficacy, is difficult to titrate, causes maternal tachycardia and depresses fetal pH and base excess. Advantages of phenylephrine include high efficacy, ease of titration and the ability to use liberal doses to maintain maternal blood pressure near normal and then prevent nausea and vomiting without causing fetal acidosis. Phenylephrine, however, may decrease maternal heart rate and cardiac output and few data are available on its use in high-risk cases. Combination of a phenylephrine infusion and rapid crystalloid cohydration is the first method described that reliably prevents hypotension. When current evidence is considered, in the authors' opinion, phenylephrine is the vasopressor that most closely meets the criteria for the best vasopressor in obstetrics.