Tissue Doppler imaging following paediatric cardiac surgery : early patterns of change and relationship to outcome

In this study, tissue Doppler imaging (TDI) was used to assess changes in ventricular function following repair of congenital heart defects. The relationship between TDI indices, myocardial injury and clinical outcome was explored. Forty-five children were studied; 35 withcardiac lesions and 10 controls. TDI was performed preoperatively, on admission to paediatric intensive care unit (PICU) and day 1. Regional myocardial Doppler signals were acquired from the right ventricle (RV), left ventricle (LV) and septum. TDI indices included: peak systolicvelocities, isovolumetric velocities (IVV) and isovolumetric acceleration (IVA). Preoperatively, bi-ventricular TDI velocities in the study groupwere reduced compared with normal controls. Postoperatively, RV velocities were significantly reduced and this persisted to day-1 (PreOp vs. PICU and day-1: 7.7+2.2 vs. 3.4+1.0, P < 0.0001 and 3.55+1.29, P < 0.0001). LV velocities initially declined but recovered towards baseline by day-1 (PreOp vs. PICU: 5.31+1.50 vs. 3.51+1.23, P < 0.0001). Isovolumetric parameters in all regions were reduced throughout the postoperative period. Troponin-I release correlated with longer X-clamp times (r=0.82, P < 0.0001) and reduced RV velocities (r=0.42, P=0.028). Reduced pre- and postoperative LV velocities correlated with longer ventilation (PreOp: r=0.54, P=0.002; PostOp: r=0.42, P=0.026). This study identified reduced postoperative RV velocities correlated with myocardial injury while reduced LV TDI correlated with longer postoperative ventilation

Maternal plasma DHA levels increase prior to 29 days post-LH surge in women undergoing frozen embryo transfer: a prospective, observational study of human pregnancy

Context: Docosahexaenoic acid (DHA) is an important fatty acid required for neurological development but its importance during early fetal neurological organogenesis is unknown. Objective: To assess plasma fatty acid changes in early pregnancy in women undergoing natural cycle-frozen embryo transfer as a means of achieving accurately-timed periconceptual sampling. Design: Women undergoing frozen embryo transfer were recruited and serial fasting blood samples were taken pre-luteinising hormone (LH) surge, and at days 18, 29 and 45 post-LH surge and fatty acids were analysed using gas chromatography. Setting: Assisted Conception Unit, Glasgow Royal Infirmary, Scotland Main outcome measures: Plasma fatty acid concentrations, influence of twin pregnancies on DHA plasma concentration. Results: In pregnant women, there was a rapid, early increase in the maternal rate of change of plasma DHA concentration observed by 29 days post-LH surge (mean±SD, from 0.1±1.3 to 1.6±2.9 nmol DHA per mL plasma per day). This early pressure to increase plasma DHA concentration was further emphasised in twin pregnancies where the increase in DHA concentration over 45 days was two-fold higher than in singleton pregnancies (mean±SD increase, 74±39 nmol/mL versus 36±40 nmol/mL). An index of delta-6 desaturase activity increased 30% and positively correlated with the rate of change of DHA concentration between day 18 and 29-post LH surge (R-squared adjusted = 41%, P=0.0002). DHA was the only fatty acid with a continual accelerated increase in plasma concentration and a positive incremental area under the curve (mean±SD, 632±911 nmol/mL x day) over the first 45 days of gestation. Conclusions: An increase in maternal plasma DHA concentration is initiated in human pregnancy prior to neural tube closure which occurs at 28 days' gestation

Pre-conception maternal erythrocyte saturated to unsaturated fatty acid ratio predicts pregnancy after natural cycle frozen embryo transfer

The environment for embryo implantation and fetal growth and development is affected by maternal nutritional, metabolic and health status. The aim of this prospective, cohort study was to test whether plasma metabolic and inflammatory biomarkers can predict pregnancy resulting from in vitro fertilisation (IVF). Women with a natural menstrual cycle undergoing frozen embryo transfer (FET) were recruited and fasting baseline blood samples were collected a mean of 3.4 days prior to the luteinising hormone (LH) surge and a non-fasting blood sample was taken on the day of FET. Ongoing pregnancy was defined by positive fetal heartbeat on ultrasound scan at day 45 post LH surge. Thirty-six pregnancies resulted from FET in 143 women. In an overall stepwise multivariable analysis, erythrocyte saturated to unsaturated fatty acid ratio was positively associated with ongoing pregnancy. A similar model incorporating day of FET covariates found that erythrocyte saturated to unsaturated fatty acid ratio, erythrocyte fatty acid average chain length and plasma log-triglycerides predicted ongoing pregnancy. In conclusion, a higher peri-conceptional saturated to unsaturated fatty acid ratio predicted ongoing pregnancy after natural cycle frozen embryo transfer and may reflect a maternal nutritional status that facilitates pregnancy success in this assisted conception scenario

Paraoxonase 2 protein is spatially expressed in the human placenta and selectively reduced in labour

Humans parturition involves interaction of hormonal, neurological, mechanical stretch and inflammatory pathways and the placenta plays a crucial role. The paraoxonases (PONs 1–3) protect against oxidative damage and lipid peroxidation, modulation of endoplasmic reticulum stress and regulation of apoptosis. Nothing is known about the role of PON2 in the placenta and labour. Since PON2 plays a role in oxidative stress and inflammation, both features of labour, we hypothesised that placental PON2 expression would alter during labour. PON2 was examined in placentas obtained from women who delivered by cesarean section and were not in labour and compared to the equivalent zone of placentas obtained from women who delivered vaginally following an uncomplicated labour. Samples were obtained from 12 sites within each placenta: 4 equally spaced apart pieces were sampled from the inner, middle and outer placental regions. PON2 expression was investigated by Western blotting and real time PCR. Two PON2 forms, one at 62 kDa and one at 43 kDa were found in all samples. No difference in protein expression of either isoform was found between the three sites in either the labour or non-labour group. At the middle site there was a highly significant decrease in PON2 expression in the labour group when compared to the non-labour group for both the 62 kDa form (p = 0.02) and the 43 kDa form (p = 0.006). No spatial differences were found within placentas at the mRNA level in either labour or non-labour. There was, paradoxically, an increase in PON2 mRNA in the labour group at the middle site only. This is the first report to describe changes in PON2 in the placenta in labour. The physiological and pathological significance of these remains to be elucidated but since PON2 is anti-inflammatory further studies are warranted to understand its role

Hypoxia Upregulates GCM1 in Human Placenta Explants

Studies in mice have shown that a variety of genes, including GCM1, regulate the differentiation of trophoblast cells. GCM1 is also expressed in the human placenta. Placental GCM1 protein has been reported to be reduced in preeclampsia. In view of the close link between hypoxia, hypoxia-reoxygenation, preeclampsia, placental development and the reported reduction in GCM1, we hypothesised that GCM1 expression would be affected by hypoxia. The aim was to determine the effects of hypoxia on GCM1 expression in the human placenta. Two model systems were used; villous explants and cultured primary cytotrophoblast cells. GCM1 protein was detectable at low levels in explants maintained for 7 h in 8 or 20% O-2. A striking increase in GCM1 was observed when villous explants were incubated for 1h in 1% O-2 (p less than 0.002). Incubation of explants for 1 h in 1% O-2 followed by re-oxygenation for 6 h in 8 or 20% O-2 resulted in a decline in GCM1 protein. Expression of GCM1 was also analysed in primary cytotrophoblast and syncytiotrophoblast cultured in 8 or 20% O-2 or reduced oxygen (1-2% O-2) conditions. GCM1 protein was not detected in any of the experimental conditions used. This study has shown that acute hypoxia increases GCM-1 protein in villous explants. The experiments with purified trophoblast do not support a role for hypoxia increasing GCM-1 in these cells under the conditions used. The present findings are in keeping with the complex effects of oxygen depending on the conditions used. The hypoxic effects on GCM1 warrant further investigation as they may provide further information on the pathogenesis of preeclampsia

HIF-1a is temporally and spatially expressed in the placenta throughout pregnancy

No abstract available

Heat shock protein 27 is spatially distributed in the human placenta and decreased during labor.

Placental oxidative stress is a feature of human labor. Heat shock proteins (HSPs) play a key role in cellular stress. We hypothesized that placental expression of the small HSP 27 would be altered during labor and expression would vary in different regions of the placenta. Six women in labor who delivered vaginally and 6 women not in labor, who were delivered by Cesarean section, were recruited. Four equally spaced pieces were sampled from the inner, middle and outer regions of each placenta (total 12 samples per placenta). HSP 27 expression was investigated by Western blot analysis and RT-PCR. For non-labor, there was less HSP 27 protein in the inner placenta region compared with both the middle region (p<0.05) and outer region (p<0.05). For labor, there was also less HSP 27 protein in the inner region compared with both the middle (p<0.02) and outer region (p<0.01). When the 3 regions of the placenta were compared for non-labor versus labor there was less HSP 27 in the labor group at both the inner (p<0.05) and middle regions (p<0.005) compared to non-labor. Similar to HSP 27 protein, there was less HSP 27 mRNA in the labor group in both the inner region (p<0.05) and middle region (p<0.02) compared to non-labor. This study suggests that placental HSP 27 may play a role in labor and is spatially controlled. The results have important implications for how data obtained from studies in the placenta can be influenced by sampling methods