scholarly journals Antenatal Steroids and the IUGR Fetus: Are Exposure and Physiological Effects on the Lung and Cardiovascular System the Same as in Normally Grown Fetuses?

2012 ◽  
Vol 2012 ◽  
pp. 1-15 ◽  
Author(s):  
Janna L. Morrison ◽  
Kimberley J. Botting ◽  
Poh Seng Soo ◽  
Erin V. McGillick ◽  
Jennifer Hiscock ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Development ◽  
Preterm Labour ◽  
Lung Surfactant ◽  
Fetal Lung ◽  
Surfactant Protein ◽  
Cardiovascular Development ◽  
Antenatal Steroids ◽  
Conflicting Evidence ◽  
Increased Risk

Glucocorticoids are administered to pregnant women at risk of preterm labour to promote fetal lung surfactant maturation. Intrauterine growth restriction (IUGR) is associated with an increased risk of preterm labour. Hence, IUGR babies may be exposed to antenatal glucocorticoids. The ability of the placenta or blood brain barrier to remove glucocorticoids from the fetal compartment or the brain is compromised in the IUGR fetus, which may have implications for lung, brain, and heart development. There is conflicting evidence on the effect of exogenous glucocorticoids on surfactant protein expression in different animal models of IUGR. Furthermore, the IUGR fetus undergoes significant cardiovascular adaptations, including altered blood pressure regulation, which is in conflict with glucocorticoid-induced alterations in blood pressure and flow. Hence, antenatal glucocorticoid therapy in the IUGR fetus may compromise regulation of cardiovascular development. The role of cortisol in cardiomyocyte development is not clear with conflicting evidence in different species and models of IUGR. Further studies are required to study the effects of antenatal glucocorticoids on lung, brain, and heart development in the IUGR fetus. Of specific interest are the aetiology of IUGR and the resultant degree, duration, and severity of hypoxemia.

Prostaglandins mediate the fetal pulmonary response to intrauterine inflammation

2012 ◽  
Vol 302 (7) ◽  
pp. L664-L678 ◽  
Author(s):  
Alana J. Westover ◽  
Stuart B. Hooper ◽  
Megan J. Wallace ◽  
Timothy J. M. Moss
Keyword(s):  
Amniotic Fluid ◽  
Lung Inflammation ◽  
Lung Surfactant ◽  
Fetal Lung ◽  
Surfactant Protein ◽  
Fetal Plasma ◽  
Pulmonary Response ◽  
Surfactant Production ◽  
Prostaglandin Dehydrogenase ◽  
Prostaglandin H

Intra-amniotic (IA) lipopolysaccharide (LPS) induces intrauterine and fetal lung inflammation and increases lung surfactant and compliance in preterm sheep; however, the mechanisms are unknown. Prostaglandins (PGs) are inflammatory mediators, and PGE2 has established roles in fetal lung surfactant production. The aim of our first study was to determine PGE2 concentrations in response to IA LPS and pulmonary gene expression for PG synthetic [prostaglandin H synthase-2 (PGHS-2) and PGE synthase (PGES)] and PG-metabolizing [prostaglandin dehydrogenase (PGDH)] enzymes and PGE2 receptors. Our second study aimed to block LPS-induced increases in PGE2 with a PGHS-2 inhibitor (nimesulide) and determine lung inflammation and surfactant protein mRNA expression. Pregnant ewes received an IA saline or LPS injection at 118 days of gestation. In study 1, fetal plasma and amniotic fluid were sampled before and at 2, 4, 6, 12, and 24 h after injection and then daily, and fetuses were delivered 2 or 7 days later. Amniotic fluid PGE2 concentrations increased ( P < 0.05) 12 h and 3–6 days after LPS. Fetal lung PGHS-2 mRNA and PGES mRNA increased 2 ( P = 0.0084) and 7 ( P = 0.014) days after LPS, respectively. In study 2, maternal intravenous nimesulide or vehicle infusion began immediately before LPS or saline injection and continued until delivery 2 days later. Nimesulide inhibited LPS-induced increases in PGE2 and decreased fetal lung IL-1β and IL-8 mRNA ( P ≤ 0.002) without altering lung inflammatory cell infiltration. Nimesulide decreased surfactant protein (SP)-A ( P = 0.05), -B ( P = 0.05), and -D ( P = 0.0015) but increased SP-C mRNA ( P = 0.023). Thus PGHS-2 mediates, at least in part, fetal pulmonary responses to inflammation.

Clearance of intra-amniotic lung surfactant: uptake and utilization by the fetal rabbit lung

1997 ◽  
Vol 273 (1) ◽  
pp. L55-L63 ◽  
Author(s):  
M. Hallman ◽  
U. Lappalainen ◽  
K. Bry
Keyword(s):  
Amniotic Fluid ◽  
Lung Surfactant ◽  
Protein A ◽  
Alveolar Epithelium ◽  
Fetal Lung ◽  
Surfactant Protein ◽  
Lung Compliance ◽  
Rabbit Lung ◽  
Lower Lung ◽  
Lung Surfactant Protein

To investigate the metabolism of intra-amniotic surfactant, surfactant containing double-labeled dipalmitoylphosphatidylcholine (DPPC) was injected in amniotic fluid on days 23-27 of gestation. Within 44 h, DPPC was distributed to the gastrointestinal tract (45.9%), fetal membranes and placenta (8.2%), fetal lung (6.6%), and liver (1.9%). DPPC uptake was higher in the upper than in the lower lung lobes. The mixture of phosphatidylglycerol and DPPC increased the uptake of DPPC that was not saturable (range 15-60 mg phospholipid). There was no detectable metabolism of DPPC taken up by the fetal lung. Surfactant protein A, originating from intra-amniotic heterplogous surfactant, was detected immunohistochemically in alveolar epithelium. Intra-amniotic surfactants did not affect the expression of surfactant protein mRNAs. Intra-amniotic surfactant (1,500-2,000 mg/kg on day 25.3) improved lung compliance of ventilated 27.0-day premature rabbits less than intratracheal surfactant at birth (75-100 mg/kg). Reutilization by the alveolar epithelium of surfactant secreted to future airspaces, airways, and amniotic fluid may be a mechanism that increases intracellular surfactant pool before birth.

scholarly journals Efficacy and safety of antenatal steroids

2018 ◽  
Vol 315 (4) ◽  
pp. R825-R839 ◽  
Author(s):  
Matthew W. Kemp ◽  
Alan H. Jobe ◽  
Haruo Usuda ◽  
Peter W. Nathanielsz ◽  
Cun Li ◽  
...  
Keyword(s):  
Preterm Infants ◽  
Nonhuman Primates ◽  
Low Cost ◽  
Personalised Medicine ◽  
Significant Proportion ◽  
Fetal Lung ◽  
Adverse Outcomes ◽  
Therapeutic Window ◽  
Antenatal Steroids ◽  
Increased Risk

Antenatal steroids (ANS) are among the most important and widely utilized interventions to improve outcomes for preterm infants. A significant body of evidence demonstrates improved outcomes in preterm infants (24–34 wk) delivered between 1 and 7 days after the administration of a single course of ANS. Moreover, ANS have the advantage of being widely available, low cost, and easily administered via maternal intramuscular injection. The use of ANS to mature the fetal lung is, however, not without contention. Their use in pregnancy is not FDA approved, and treatment doses and regimens remain largely unoptimized. Their mode of use varies considerably between countries, and there are lingering concerns regarding the safety of exposing the fetus to high doses of exogenous steroids. A significant proportion of women deliver outside the 1- to 7-day therapeutic window after ANS treatment, and this delay may be associated with an increased risk of adverse outcomes for both mother and baby. Today, animal-based studies are one means by which key questions of dosing and safety relating to ANS may be resolved, allowing for further refinement(s) of this important therapy. Complementary approaches using nonhuman primates, sheep, and rodents have provided invaluable advances to our understanding of how exogenous steroid exposure impacts fetal development. Focusing on these three major model groups, this review highlights the role of three key animal models (sheep, nonhuman primates, rodents) in the development of antenatal steroid therapy, and provides an up-to-date synthesis of current efforts to refine this therapy in an era of personalised medicine.

High altitude hypoxia and blood pressure dysregulation in adult chickens

2012 ◽  
Vol 4 (1) ◽  
pp. 69-76 ◽  
Author(s):  
E. A. Herrera ◽  
C. E. Salinas ◽  
C. E. Blanco ◽  
M. Villena ◽  
D. A. Giussani
Keyword(s):  
Blood Pressure ◽  
High Altitude ◽  
Arterial Blood Pressure ◽  
Cardiovascular Function ◽  
Dependent Manner ◽  
Cardiovascular Development ◽  
Placental Perfusion ◽  
Arterial Blood ◽  
Increased Risk

Although it is accepted that impaired placental perfusion in complicated pregnancy can slow fetal growth and programme an increased risk of cardiovascular dysfunction at adulthood, the relative contribution of reductions in fetal nutrition and in fetal oxygenation as the triggering stimulus remains unclear. By combining high altitude (HA) with the chick embryo model, we have previously isolated the direct effects of HA hypoxia on embryonic growth and cardiovascular development before hatching. This study isolated the effects of developmental hypoxia on cardiovascular function measured in vivo in conscious adult male and female chickens. Chick embryos were incubated, hatched and raised at sea level (SL, nine males and nine females) or incubated, hatched and raised at HA (seven males and seven females). At 6 months of age, vascular catheters were inserted under general anaesthesia. Five days later, basal blood gas status, basal cardiovascular function and cardiac baroreflex responses were investigated. HA chickens had significantly lower basal arterial PO2 and haemoglobin saturation, and significantly higher haematocrit than SL chickens, independent of the sex of the animal. HA chickens had significantly lower arterial blood pressure than SL chickens, independent of the sex of the animal. Although the gain of the arterial baroreflex was decreased in HA relative to SL male chickens, it was increased in HA relative to SL female chickens. We show that development at HA lowers basal arterial blood pressure and alters baroreflex sensitivity in a sex-dependent manner at adulthood.

Intrafetal glucose infusion alters glucocorticoid signaling and reduces surfactant protein mRNA expression in the lung of the late-gestation sheep fetus

2014 ◽  
Vol 307 (5) ◽  
pp. R538-R545 ◽  
Author(s):  
Erin V. McGillick ◽  
Janna L. Morrison ◽  
I. Caroline McMillen ◽  
Sandra Orgeig
Keyword(s):  
Mrna Expression ◽  
Fetal Lung ◽  
Glucose Transporters ◽  
Surfactant Protein ◽  
Glucose Infusion ◽  
Late Gestation ◽  
Lung Maturation ◽  
Increased Risk ◽  
Sheep Fetus ◽  
Diabetic Mothers

Increased circulating fetal glucose and insulin concentrations are potential inhibitors of fetal lung maturation and may contribute to the pathogenesis of respiratory distress syndrome (RDS) in infants of diabetic mothers. In this study, we examined the effect of intrafetal glucose infusion on mRNA expression of glucose transporters, insulin-like growth factor signaling, glucocorticoid regulatory genes, and surfactant proteins in the lung of the late-gestation sheep fetus. The numerical density of the cells responsible for producing surfactant was determined using immunohistochemistry. Glucose infusion for 10 days did not affect mRNA expression of glucose transporters or IGFs but did decrease IGF-1R expression. There was reduced mRNA expression of the glucocorticoid-converting enzyme HSD11B-1 and the glucocorticoid receptor, potentially reducing glucocorticoid responsiveness in the fetal lung. Furthermore, surfactant protein ( SFTP) mRNA expression was reduced in the lung following glucose infusion, while the number of SFTP-B-positive cells remained unchanged. These findings suggest the presence of a glucocorticoid-mediated mechanism regulating delayed maturation of the surfactant system in the sheep fetus following glucose infusion and provide evidence for the link between abnormal glycemic control during pregnancy and the increased risk of RDS in infants of uncontrolled diabetic mothers.

Differential regulation of SP-A1 and SP-A2 genes by cAMP, glucocorticoids, and insulin

1998 ◽  
Vol 274 (2) ◽  
pp. L177-L185 ◽  
Author(s):  
A. R. Kumar ◽  
J. M. Snyder
Keyword(s):  
Cell Line ◽  
Lung Surfactant ◽  
Protein A ◽  
Fetal Lung ◽  
Surfactant Protein ◽  
Model Systems ◽  
Mrna Levels ◽  
Mrna Transcripts ◽  
Lung Surfactant Protein ◽  
Human Fetal Lung

In the human fetal lung, surfactant protein A (SP-A) is encoded by two highly similar genes, SP-A1 and SP-A2, which are developmentally and hormonally regulated. Using primer extension analysis, we evaluated the levels of SP-A1 and SP-A2 mRNA transcripts in human fetal lung explants and in a human adult lung adenocarcinoma cell line (H441 cells) cultured in the absence or presence of either dibutyryladenosine 3′,5′-cyclic monophosphate (DBcAMP, 1 mM), dexamethasone (10−7 M), or insulin (2.5 μg/ml). In the human fetal lung explants, the content of SP-A1 mRNA was approximately four times that of SP-A2 mRNA. DBcAMP increased SP-A1 mRNA levels by 100% and SP-A2 mRNA levels by 500%, thus reducing the ratio of SP-A1 mRNA to SP-A2 mRNA to ∼1:1. Dexamethasone inhibited all of the SP-A1 and SP-A2 mRNA transcripts to the same extent, by ∼70%, whereas insulin inhibited all SP-A mRNA transcripts by ∼60%. The ratio of SP-A1 to SP-A2 mRNA in dexamethasone- or insulin-treated explants was the same as the ratio observed in controls. In the H441 cells, SP-A1 mRNA levels were ∼1.5 times that of SP-A2 mRNA levels. DBcAMP increased both SP-A1 and SP-A2 mRNA levels by 100%. Dexamethasone inhibited SP-A1 mRNA levels in the cell line by 60%, whereas SP-A2 mRNA levels were not significantly affected. Insulin inhibited SP-A1 mRNA levels in the cell line by 40% without affecting SP-A2 mRNA levels. These findings suggest that the two human SP-A genes are regulated differently in the two model systems.

Sex Differences in Cardiovascular Reactivity

2009 ◽  
Vol 23 (2) ◽  
pp. 77-84 ◽  
Author(s):  
Matthew C. Whited ◽  
Kevin T. Larkin
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Sex Differences ◽  
Gender Roles ◽  
Cardiovascular Reactivity ◽  
Task Type ◽  
Conflict Task ◽  
Men And Women ◽  
Conflicting Evidence ◽  
Blood Pressure Responses

Sex differences in cardiovascular reactivity to stress are well documented, with some studies showing women having greater heart rate responses than men, and men having greater blood pressure responses than women, while other studies show conflicting evidence. Few studies have attended to the gender relevance of tasks employed in these studies. This study investigated cardiovascular reactivity to two interpersonal stressors consistent with different gender roles to determine whether response differences exist between men and women. A total of 26 men and 31 women were assigned to either a traditional male-oriented task that involved interpersonal conflict (Conflict Task) or a traditional female-oriented task that involved comforting another person (Comfort Task). Results demonstrated that women exhibited greater heart rate reactions than men independent of the task type, and that men did not display a higher reactivity than women on any measure. These findings indicate that sex of participant was more important than gender relevance of the task in eliciting sex differences in cardiovascular responding.

The Effect of Exercise and Distraction on Blood Pressure Recovery Following an Anger-Provoking Stressor in Normotensive Young Adults

2015 ◽  
Vol 29 (2) ◽  
pp. 45-54 ◽  
Author(s):  
Faye S. Routledge ◽  
Judith A. McFetridge-Durdle ◽  
Marilyn Macdonald ◽  
Lynn Breau ◽  
Tavis Campbell
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Health ◽  
Exercise Intervention ◽  
Recovery Period ◽  
Intervention Group ◽  
Exercise Group ◽  
State Anger ◽  
Increased Risk ◽  
Anger Reactivity ◽  
Quiet Sitting

Ruminating about a prior anger provoking event is found to elevate blood pressure (BP) and delay BP recovery. Delayed BP recovery may be associated with increased risk of hypertension. Interventions that improve BP recovery may be beneficial for cardiovascular health. The purposes of this study were to evaluate the influence of rumination and anger on BP reactivity and recovery, to compare the effect of an exercise intervention or distraction intervention on BP recovery and to explore if exercise improved BP recovery by distracting participants from stressor-related rumination and anger. Healthy, normotensive participants (n = 79, mean age 22.2 ± 4.0 years) underwent an anger-recall interview stressor task, 3 min of exercise (walking), distraction (reading) or no-intervention (quiet sitting) and a 15 min recovery period. State anger reactivity was associated with Δ diastolic (D) BP reactivity and approached significance with Δ systolic (S) BP reactivity. Trait rumination was associated with greater SBP during recovery. Δ SBP recovery did not differ between the exercise, distraction and no-intervention groups. Although there were no differences in Δ DBP recovery between the exercise and no-intervention groups, distraction improved Δ DBP recovery compared to the exercise intervention but not the no-intervention. The proportion of anger-related thoughts (state rumination) in the exercise group did not differ from the distraction or no-intervention groups. However, a smaller proportion of participants in the distraction intervention reported an anger-related thought during recovery compared to the no-intervention group with 76% of their thoughts relating to the provided distraction. Overall, post-stressor exercise was not found to improve BP recovery while reading was effective at distracting individuals from angry thoughts (state rumination) but had no effect on BP compared to no-intervention.

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