Reduction In Placental Blood Flow Research Articles

An expert review of environmental heat exposure and stillbirth in the face of climate change: Clinical implications and priority issues.

Exposure to extreme heat in pregnancy increases the risk of stillbirth. Progress in reducing stillbirth rates has stalled, and populations are increasingly exposed to high temperatures and climate events that may further undermine health strategies. This narrative review summarises the current clinical and epidemiological evidence of the impact of maternal heat exposure on stillbirth risk. Out of 20 studies, 19 found an association between heat and stillbirth risk. Recent studies based in low- to middle-income countries and tropical settings add to the existing literature to demonstrate that all populations are at risk. Additionally, both short-term heat exposure and whole-pregnancy heat exposure increase the risk of stillbirth. A definitive threshold of effect has not been identified, as most studies define exposure as above the 90th centile of the usual temperature for that population. Therefore, the association between heat and stillbirth has been found with exposures from as low as >12.64°C up to >46.4°C. The pathophysiological pathways by which maternal heat exposure may lead to stillbirth, based on human and animal studies, include both placental and embryonic or fetal impacts. Although evidence gaps remain and further research is needed to characterise these mechanistic pathways in more detail, preliminary evidence suggests epigenetic changes, alteration in imprinted genes, congenital abnormalities, reduction in placental blood flow, size and function all play a part. Finally, we explore this topic from a public health perspective; we discuss and evaluate the current public health guidance on minimising the risk of extreme heat in the community. There is limited pregnancy-specific guidance within heatwave planning, and no evidence-based interventions have been established to prevent poor pregnancy outcomes. We highlight priority research questions to move forward in the field and specifically note the urgent need for evidence-based interventions that are sustainable.

Transgenerational effects of maternal exposure to nicotine on structures of pituitary-gonadal axis of rats

Smoking can lead to several diseases and cause a reduction in fertility in men and women. Among the various components of cigarettes harmful during pregnancy, nicotine stands out. It can cause a reduction in placental blood flow, compromising the development of the baby with neurological, reproductive and endocrine consequences. Thus, we aimed to evaluate the effects of nicotine on the pituitary-gonadal axis of rats exposed during pregnancy and breastfeeding (1st generation - F1), and whether the possible damage observed would reach the 2nd generation (F2). Pregnant Wistar rats received 2 mg/kg/day of nicotine throughout the entire gestation and lactation. Part of the offspring was evaluated on the first neonatal day (F1) for macroscopic, histopathological and immunohistochemical analyses of brain and gonads. Another part of the offspring was kept until 90 days-old for mating and obtainment of progenies that had the same parameters evaluated at the end of pregnancy (F2). The occurrence of malformations was more frequent and diversified in nicotine-exposed F2. Brain alterations, including reduced size and changes in cell proliferation and death, were seen in both generations of nicotine-exposed rats. Male and female gonads of F1 exposed rats were also affected. The F2 rats showed reduced cellular proliferation and increased cell death on the pituitary and ovaries, besides increased anogenital distance in females. The number of mast cells was not enough altered to indicate an inflammatory process in brain and gonads. We conclude that prenatal exposure to nicotine causes transgenerational alterations in the structures of pituitary-gonadal axis in rats.

SARS-CoV-2 Infection during Pregnancy and Histological Alterations in the Placenta.

(1) Background: Despite the high number of cases of COVID-19 during pregnancy, SARS-CoV-2 congenital infection is rare. The role of the placenta as a barrier preventing the transmission of SARS-CoV-2 from the mother to the fetus is still being studied. This study aimed to evaluate the impact of SARS-CoV-2 infection on placental tissue. (2) Methods: This was a transversal monocentric observational study. In the study, we included pregnant women with COVID-19 who delivered at “Sfântul Pantelimon” Clinical Emergency Hospital between 1 April 2020 and 30 March 2022. Histological analyses, both macroscopic and microscopic, were performed for placentas that came from these cases. (3) Results: To date, a characteristic placental lesion has not been clearly demonstrated, but most findings include features of maternal and fetal vascular malperfusion, which probably reflect the reduction in placental blood flow due to low oxygen level from the hypoxic respiratory disease and underlying hypercoagulable state induced by the COVID-19 infection. (4) Conclusions: The histopathological aspects found in placentas that came from COVID-19-positive pregnant women are common for many other diseases, but when they are found together, they are highly suggestive for viral infectious involvement of the placenta.

Resistance Training Does Not Decrease Placental Blood Flow During Valsalva Maneuver: A Novel Use of 3D Doppler Power Flow Ultrasonography.

The Valsalva maneuver may increase maternal blood pressure and intra-abdominal pressure, resulting in decreased blood flow to the fetus during resistance training. There is no significant reduction in placental blood flow in pregnancy during resistance training in recreational athletes, as documented by a 3-dimensional power flow Doppler ultrasonography. Cohort. Level 3. A cohort of healthy women who participated in recreational athletics was enrolled in a prospective study to assess placental blood flow during a resistance exercise. A 1 repetition maximum (1RM, up to 50 lb) was determined through a modified chest press as a marker of heavy resistance training. Three-dimensional volume measurements and power Doppler flow were determined at the rest phase and during the 1RM lift phase. The vascular flow index (VFI) was calculated to determine placental perfusion during each phase. A total of 22 women participated. The mean age of participants was 31 years. Gestational age ranged from 13 to 28 weeks. Average 1RM weight lifted was 30 lb. Four women (18%) were able to lift 50 lb, the maximum weight that the study allowed. The remaining 18 women (82%) lifted their true 1RM. Mean VFI during lift phase was 2.185 compared with 2.071 at rest (P = 0.03). There was a slight mean increase in VFI during lift phase, 0.114 (95% CI 0.009-0.182) from 2.071 to 2.185 with lifting (P = 0.03). The 15 women who participated in structured exercise had a mean VFI at rest and during the lift phase of 2.031 and 2.203, respectively (P = 0.01). Three-dimensional power flow Doppler imaging can guide resistance training during pregnancy to prevent fetal injury due to hypoperfusion. Resistance training up to an RM1 of 50 lb did not result in a significant reduction of placental blood flow from resting state in the study population. This technique may be used to guide training parameters among pregnant athletes.

First trimester alcohol exposure alters placental perfusion and fetal oxygen availability affecting fetal growth and development in a non-human primate model

Prenatal alcohol exposure leads to impaired fetal growth, brain development, and stillbirth. Placental impairment likely contributes to these adverse outcomes, but the mechanisms and specific vasoactive effects of alcohol that links altered placental function to impaired fetal development remain areas of active research. Recently, we developed magnetic resonance imaging techniques in nonhuman primates to characterize placental blood oxygenation through measurements of T2* and perfusion using dynamic contrast-enhanced magnetic resonance imaging. The objective of this study was to evaluate the effects of first-trimester alcohol exposure on macaque placental function and to characterize fetal brain development invivo. Timed-pregnant Rhesus macaques (n=12) were divided into 2 groups: control (n=6) and ethanol exposed (n=6). Animals were trained to self-administer orally either 1.5 g/kg/d of a 4% ethanol solution (equivalent to 6 drinks/d) or an isocaloric control fluid from preconception until gestational day 60 (term is G168). All animals underwent Doppler ultrasound scanning followed by magnetic resonance imaging that consisted of T2* and dynamic contrast-enhanced measurements. Doppler ultrasound scanning was used to measure uterine artery and umbilical vein velocimetry and diameter to calculate uterine artery volume blood flow and placental volume blood flow. After noninvasive imaging, animals underwent cesarean delivery for placenta collection and fetal necropsy at gestational day 110 (n=6) or 135 (n=6). Fetal weight and biparietal diameter were significantly smaller in ethanol-exposed animals compared with control animals at gestational day 110. By Doppler ultrasound scanning, placental volume blood flow was significantly lower (P=.04) at gestational day 110 in ethanol-exposed vs control animals. A significant reduction in placental blood flow was evident by dynamic contrast-enhanced magnetic resonance imaging. As we demonstrated recently, T2* values vary throughout the placenta and reveal gradients in blood deoxyhemoglobin concentration that range from highly oxygenated blood (long T2*) proximal to spiral arteries to highly deoxygenated blood (short T2*). Distributions ofT2*throughout the placenta show significant global reduction in T2* (andhence high blood deoxyhemoglobin concentration) in ethanol-exposed vs control animals at gestational day 110 (P=.02). Fetal brain measurements indicated impaired growth and development at gestational day 110, but less so at gestational day 135 in ethanol-exposed vs control animals. Chronic first-trimester ethanol exposure significantly reduces placental perfusion and oxygen supply to the fetal vasculature later in pregnancy. These perturbations of placental function are associated with fetal growth impairments. However, differences between ethanol-exposed and control animals in placental function and fetal developmental outcomes were smaller at gestational day 135 than at gestational day 110. These findings are consistent with placental adaptation to early perturbations that allow for compensated placental function and maintenance of fetal growth.

Recapitulation of characteristics of human placental vascular insufficiency in a novel mouse model

ObjectiveWe tested the effects of selective reduction of placental blood flow by mesenteric uterine artery branch ligation (MUAL) resulting in fetal growth restriction (FGR). MethodsTimed mated C57BL/6J Day(D) 18 dams were divided into two groups: MUAL (n = 18); and control-sham (n = 18). Pups were delivered on D20, cross-fostered to surrogate CD-1 mothers for 4 weeks, and followed for 8 weeks. Outcome data included birth and placental weight, postnatal growth, placental volume determined by stereology, quantification of placental insulin-like growth factors-1(IGF-1) and IGF-2 and IGF binding proteins(IGFBP 2 and 6) by ELISA and gene expression by qPCR and GeneChip microarray analysis. ResultsCompared with control, MUAL had an 11% reduction in mean birth weight (1.06 ± 0.13 g vs. 0.94 ± 0.13 g, p < 0.001) but no difference in placental weight. At 4 weeks of age, mean body weights of MUAL pups were significantly lower than sham. By 8 weeks, males but not females MUAL mice achieved equivalent mean body weight to control. Placental labyrinth depth, volume, and placental gene expression of IGF-1 and 2 were significantly reduced by MUAL. In contrast, placental protein level of IGFBP-2 and 6 were significantly elevated in the MUAL. Genomic expression analysis demonstrated that MUAL pups significantly up-regulated genes that were associated with apoptosis and growth pathways. ConclusionThis novel mouse animal model of FGR using selective ligation recapitulates multiple characteristics of placental vascular insufficiency (PI) in humans. This is the first non-genetic mouse model of PI which offers its application in transgenic mice to better study the underlying mechanisms in PI. CondensationA new mouse model of placental vascular insufficiency by selective ligation of mesenteric uterine artery branch recapitulates multiple findings observed in human placental vascular insufficiency.

Does Antenatal Maternal Psychological Distress Affect Placental Circulation in the Third Trimester?

IntroductionSome types of antenatal maternal psychological distress may be associated with reduced fetal growth and birthweight. A stress-mediated reduction in placental blood flow has been suggested as a mechanism. Previous studies have examined this using ultrasound-derived arterial resistance measures in the uterine (UtA) and umbilical (UA) arteries, with mixed conclusions. However, a reduction in placental volume blood flow may occur before changes in arterial resistance measures are seen. Fetoplacental volume blood flow can be quantified non-invasively in the umbilical vein (UV). Our objective was to study whether specific types of maternal psychological distress affect the placental circulation, using volume blood flow quantification in addition to arterial resistance measures.MethodsThis was a prospective observational study of 104 non-smoking pregnant women (gestational age 30 weeks) with uncomplicated obstetric histories. Psychological distress was measured by General Health Questionnaire-28 (subscales anxiety and depression) and Impact of Event Scale-22 (subscales intrusion, avoidance and arousal). UtA and UA resistance measures and UV volume blood flow normalized for fetal abdominal circumference, were obtained by Doppler ultrasound.ResultsIES intrusion scores above the mean were associated with a reduction in normalized UV volume blood flow (corresponding to –0.61 SD; P = 0.003). Adjusting for UA resistance increased the strength of this association (difference –0.66 SD; P<0.001). Other distress types were not associated with UV volume blood flow. Maternal distress was not associated with arterial resistance measures, despite adjustment for confounders.ConclusionsIntrusive thoughts and emotional distress regarding the fetus were associated with reduced fetoplacental volume blood flow in third trimester. Uterine and umbilical artery resistance measures were not associated with maternal distress. Our findings support a decrease in fetoplacental blood flow as a possible pathway between maternal distress and reduced fetal growth.

Alteration of mitochondrial function in adult rat offspring of malnourished dams

Under-nutrition as well as over-nutrition during pregnancy has been associated with the development of adult diseases such as diabetes and obesity. Both epigenetic modifications and programming of the mitochondrial function have been recently proposed to explain how altered intrauterine metabolic environment may produce such a phenotype. This review aims to report data reported in several animal models of fetal malnutrition due to maternal low protein or low calorie diet, high fat diet as well as reduction in placental blood flow. We focus our overview on the β cell. We highlight that, notwithstanding early nutritional events, mitochondrial dysfunctions resulting from different alteration by diet or gender are programmed. This may explain the higher propensity to develop obesity and diabetes in later life.

Placental pathology in fetal growth restriction

Objectives One of the causes of intrauterine fetal growth restriction (FGR) can be pathology of the placenta. The aim of this study was to compare macroscopic and microscopic changes of the placentas from intrauterine growth restricted fetuses with those from normally developed fetuses, in order to test the hypothesis that vascular damage due to decreased maternal vascular perfusion may be responsible for FGR. Study design Between May 2007 and December 2008 we performed detailed macroscopic and histological examination of singleton placentas of 50 consecutive neonates with fetal growth restriction (FGR group) and compared them to 50 normal fetuses, born next to an FGR case, as a control group. Results Gestational age, birth weight, spontaneous delivery rate, mean weight of the placenta and the fetal–placental weight ratio were all lower in the FGR group than in the control group ( p < 0.05). Thickening of the villous trophoblastic basal membrane, incidence of villous infarction, presence of thrombi or haematomas and the incidence of villitis were more common in the FGR group than in the controls ( p < 0.05). There were, however, no significant differences in perivillous fibrin deposition, stromal fibrosis and cytotrophoblast proliferation between the groups. In FGR women who smoked, intervillous haematomas and villous infarction were more common ( p < 0.05) than in controls. Conclusions All macroscopic and microscopic pathological changes associated with FGR were directly linked to reduction of placental blood flow. As smoking is a main risk factor for these placental abnormalities these results emphasize the need to persuade women to quit smoking not only during pregnancy, but even better long before pregnancy.

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.

Increased Myogenic Reactivity of Resistance‐sized Mesenteric Arteries from Pregnant Rats with Episodic Reductions in Uteroplacental Perfusion

Pregnancy is associated with increased placental blood flow (BF) to the developing fetus. A central component of preeclampsia is thought to be a reduction in placental BF leading to altered vascular reactivity. It is suggested that short term elevations in blood pressure may lead to periodic reductions in uteroplacental blood flow (UBF) and this may play a role in preeclampsia. The purpose of this study was to develop a gravid rat model characterized by episodic reductions in UBF to elucidate the role of periodic decreases in UBF on vascular reactivity. We used pregnant Sprague Dawley rats and subjected them to Sham or aortic occlusion surgery on Day 14 of gestation. Aortic occlusion surgery consisted of implantation of a silastic vascular occluder around the abdominal aorta along with silver clips (0.106mm ID) around the uterine‐ovarian arteries. Aortic occlusion animals were subjected to 5 days of reduced UBF (40% reduction) for 1 hour each session. On Day 21, second order mesenteric arteries were mounted on a pressurized arteriograph. Myogenic reactivity of small mesenteric arteries was increased in Occluder animals compared to Sham (p&lt;0.05). This data suggest that episodic reductions in UBF may mimic some of the characteristics of preeclampsia including altered vascular reactivity toward a constrictive phenotype. Aortic occlusion may be a new model for investigating mechanisms associated with reduced UBF.

Potential Cell Signalling Mechanisms Involved in Differential Placental Angiogenesis in Mild and Severe Pre-Eclampsia

Fetal and neonatal morbidity and mortality is high in severe pre-eclampsia compared with mild pre-eclampsia and normotensive pregnancies. Causes for these fetal disturbances had been associated with iatrogenic prematurity and reduction in placental blood flow. Actual evidences suggest that in severe (early-onset) pre-eclampsia a reduction in placental angiogenesis could be a mechanism responsible for the reduced placental blood flow, while in mild (late-onset) pre-eclampsia normal placental blood flow could result from either no alteration or increased placental angiogenesis, or reduced vessel resistance. Since adenosine is involved in endothelium proliferation and angiogenesis, and umbilical and maternal blood level of this nucleoside is elevated in pre-eclampsia compared with normal pregnancies, it is feasible that placental angiogenesis in mild and/or severe pre-eclampsia involves adenosine-dependent cell signaling mechanisms. There are not reports regarding adenosine role in placental angiogenesis neither in normal nor in pathological pregnancies. However, it is well established that adenosine stimulates adenosine receptors triggering expression of angiogenic factors such as vascular endothelial growth factor (VEGF). VEGF stimulates VEGF receptors type 1 and 2, activating signaling cascades that involve increased synthesis of endothelial-derived nitric oxide (NO). On the other hand, the soluble VEGF receptor type 1 (sFlt-1), whose plasma concentration is increased in severe compared with mild pre-eclampsia, reduces angiogenesis, spotting sFlt-1 as a factor that could potentially be involved in this phenomenon. This review focuses on the available evidence regarding a potential differential mechanism of placental angiogenesis in mild compared with severe pre-eclampsia, and analyzes the potential role of adenosine/VEGF/VEGF receptors/NO signaling cascade in this phenomenon.

Reduction of Maternal Adrenal Steroids Results in Increased VEGF Protein Without Increased eNOS in the Ovine Placenta

Fetal sheep studies have shown that reduced maternal cortisol or aldosterone levels alter placental morphology, with a reduction in placental blood flow. We have now tested the hypothesis that changes in placental morphology with relative adrenal hypoadrenalism are associated with changes in vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS). Four groups of late gestation pregnant ewes with singleton fetuses were studied; controls (intact adrenals), normal cortisol and aldosterone (ewes adrenalectomized and replaced with normal cortisol and aldosterone levels), low cortisol (ewes adrenalectomized and replaced with low cortisol levels), and low aldosterone (ewes adrenalectomized and replaced with low aldosterone levels). The placenta was categorized into A, B, C or D type placentomes. There were significantly more B and C type placentomes in the adrenalectomized groups than in controls. Overall, B types had more VEGF mRNA than A types. VEGF protein levels corresponding to a 23kDa band were highest in low aldosterone animals in A and C type placentomes. VEGF protein levels corresponding to a 47kDa band were higher in C type placentomes than A types; protein levels were also higher overall in low cortisol animals compared to controls. Fetoplacental eNOS protein levels were lower in the adrenalectomized groups than in controls. In conclusion, our results indicate that increases in cotyledonary VEGF164 protein were associated with fetal tissue overgrowth in the placenta when the pregnancy-induced increase in adrenal steroids was prevented in the ewe. However, cotyledonary eNOS protein was suppressed with reduced maternal adrenal steroids, which is consistent with the reduced placental perfusion previously observed in this model.

In vivo dynamic MRI measurement of the noradrenaline-induced reduction in placental blood flow in mice

We developed a new model for in vivo placental perfusion measurements based on dynamic MRI in mice. As noradrenaline has been implicated in the pathogenesis of preeclampsia, we examined whether it reduced placental perfusion in mice, and whether such a reduction could be detected with our MRI model.

In Vivo Dynamic MRI Measurement of the Noradrenaline-induced Reduction in Placental Blood Flow in Mice

Purpose We developed a new model for in vivo placental perfusion measurements based on dynamic MRI in mice. As noradrenaline has been implicated in the pathogenesis of preeclampsia, we examined whether it reduced placental perfusion in mice, and whether such a reduction could be detected with our MRI model. Materials and methods Mice at 16 days of gestation were injected intramuscularly with saline or noradrenaline solution. A conventional gadolinium chelate was then injected IV, and a single-slice T1-weighed 2D Fast SPGR sequence was acquired for 200 s. Signal intensity was measured on all the images and converted into contrast agent tissue concentrations in the maternal left ventricle (input function) and placentas. A one-compartment model was developed using compartmental and numerical modeling software. Mean blood flow ( F) was calculated from a transfer constant. Results Twenty-six mice were studied, yielding a total of 55 MRI measurements of placental perfusion (29 in the control group and 26 in the noradrenaline group). Mean placental blood flow ( F) was significantly lower in the noradrenaline group (0.72 ± 0.84 ml/min/g of placenta) than in the control group (1.26 ± 0.54 ml/min/g of placenta). Conclusion Noradrenaline reduces placental perfusion in mice. Our MRI dynamic model might be useful for detecting and investigating abnormal placental blood flow, thereby avoiding the need for invasive procedures and animal sacrifice.

NO modulates fetoplacental blood flow distribution and whole body oxygen extraction in fetal sheep.

It is unknown if nitric oxide (NO) influences the relative level of the left (LV) and right ventricular (RV) outputs, the blood flow distribution between the body and placenta, or whole body O2 extraction and O2 consumption in the fetus. To address these questions eight fetal lambs were chronically instrumented at 128-134 days gestation (term 147 days), and blood flows were measured with radioactive microspheres 3-4 days later at baseline and after inhibition of NO synthesis with N omega-nitro-L-arginine (L-NNA, 10 and 25 mg/kg i.v.). L-NNA progressively reduced the combined ventricular output (P < 0.005) but did not alter the relative levels of the LV and RV outputs. Fetal body blood flow fell by 31% after 10 mg/kg L-NNA (P < 0.005), but a reduction in placental blood flow (P < 0.005) was smaller (20%) and not observed until 25 mg/kg L-NNA. Whole body O2 extraction increased by 71% after 10 mg/kg L-NNA (P < 0.005) and did change further at 25 mg/kg L-NNA, whereas whole body O2 consumption rose by 15% at 10 mg/kg L-NNA (P < 0.05) and returned to baseline at 25 mg/kg L-NNA. These results suggest that, as well as reducing the combined ventricular output, inhibition of fetal NO synthesis redistributes systemic blood flow toward the placenta and increases fetal body O2 extraction. The latter initially increases whole body O2 consumption and then maintains it at near baseline levels after a fall in placental perfusion.

Endothelin in Primate Pregnancy and an Experimental Preeclampsia-Like Syndrome

Objectives: To examine the serial changes in circulating endothelin concentration as primate pregnancy advances. To compare peripheral venus and uterine circulations in normal pregnancy and to determine the usefulness of an experimental preeclampsia-like syndrome in examining the placental contribution to total endothelin concentration.Design: Serial measurements of arterial, venous, and uteroplacental endothelin concentration were performed monthly in baboon pregnancy. Endothelin was also measured after reduction in placental blood flow by limited uterine artery ligation and in a sham-operated control.Methods: Ten baboon pregnancies were examined prospectively. Plasma for endothelin concentration was collected from maternal systemic sources and the uteroplacental bed. Endothelin concentration was determined in two operated and a sham-operated controls after reduction of uteroplacental blood flow by angiographically directed selective ligation of a branch of the uterine artery. Signs of a preeclampsia-like syndrome were also examined in these animals.Results: Endothelin concentration progressively decreased as normal pregnancy advanced, with the lowest concentration recorded prior to delivery. After uterine artery ligation, an animal with signs of a severe preeclampsia-like syndrome demonstrated a rise in arterial endothelin concentration at the time of delivery. This did not appear to arise from the uteroplacental circulation.Conclusions: Elevated endothelin concentrations in human preeclampsia, a late pregnancy event, should be interpreted in light of decreased concentrations at this time in normal primate pregnancy. Endothelin may be a marker of disease severity in human preeclampsia.

Computerized microscope morphometry of umbilical vessels from pregnancies with intrauterine growth retardation and abnormal umbilical artery doppler

Computerized microscope morphometry was used to study cross sections from the vessels of the umbilical cord in placentas of patients with intrauterine growth retardation (IUGR) that displayed either normal or abnormal umbilical arteries (UA) Doppler flow velocity waveforms (FVW). Cords from 63 eutrophic fetuses with normal Doppler (controls), 47 IUGR fetuses with normal Doppler and 32 IUGR fetuses with abnormal Doppler underwent morphometric analysis using a highly optimized microscope environment (HOME) and “CordHOME” software. IUGR with an accompanying normal Doppler versus control showed a reduction of Wharton jelly and both the total and lumen vein areas. IUGR with an accompanying pathological Doppler showed a comparable reduction in wall thickness and areas of every vessel. These findings indicate that the hypoplastic umbilical vessels are associated with an increase in placental vascular resistance that may be the consequence of underdevelopment in response to a chronic reduction in placental blood flow.

Fetal sheep endocrine responses to sustained hypoxemic stress after chronic fetal placental embolization.

The purpose of this study was to determine the endocrine and circulatory responses of the ovine fetus, near term, to sustained hypoxemic stress superimposed on chronic hypoxemia. Fetal sheep were chronically embolized (n = 7) for 10 days between 0.84 and 0.91 of gestation via the descending aorta until arterial oxygen content was decreased by approximately 30%. Control animals (n = 8) received saline only. On experimental day 10, both groups were embolized over a 6-h period until fetal arterial pH decreased to approximately 7.00. Regional distribution of lower body blood flows was measured on day 10, before and at the end of acute embolization. On day 10, the chronically embolized group had lower arterial oxygen content (P < 0.05), Po2 (P < 0.01), and placental blood flow (P < 0.05) than controls and higher prostaglandin E2 (PGE2) and norepinephrine plasma concentrations (both P < 0.05). In response to a superimposed sustained hypoxemic stress, there was a twofold greater increase in PGE2 in the chronically embolized group than in the control group (P < 0.05). However, the increase in fetal plasma cortisol in response to superimposed hypoxemic stress was similar in both groups, despite significantly lower adrenocorticotropic hormone and adrenal cortex blood flow responses in the chronically hypoxemic group (both P < 0.05). We conclude that PGE2 response to a sustained superimposed reduction in placental blood flow, leading to metabolic acidosis, is enhanced under conditions of chronic hypoxemia and may play an important role for the maintenance of the fetal cortisol response to an episode of superimposed acute stress.

Effects of felodipine on utero-placental blood flow in normotensive rabbits.

The utero-placental blood flow was investigated in anaesthetized normotensive pregnant rabbits after repeated administration of a high dose of the antihypertensive calcium antagonist felodipine and in untreated controls. By means of the microsphere technique blood flow was also determined in the lungs, skin, intestine, skeletal muscle and kidneys during chloralose anaesthesia. Felodipine reduced mean arterial blood pressure, which was associated with a marked reduction in vascular resistance in the skeletal muscle vascular bed, where blood flow was increased seven-fold. In contrast, blood flow to placentae and kidneys were reduced. The pronounced reduction in placental blood flow may limit foetal nutrition and hence explain reported foetal digital defects after administration of high doses of felodipine to pregnant normotensive rabbits.