ABSTRACT

Blockade of small-conductance Ca (2)(+)-activated K(+) channels (SK(Ca)) and intermediate conductance Ca(2)(+)-activated K(+) channels (IK(Ca)) can cause inhibition of endothelium-dependent hyperpolarizing factor (EDHF) in many vascular beds from animals, but there is a relative paucity of data in human vessels. Systemic arteries, isolated from women with healthy pregnancies, relax to the endothelial-dependent agonist bradykinin via a nonprostacyclin and non-nitric oxide pathway attributable to EDHF. Therefore, in this study, the authors investigated the effect of pharmacological blockade of SK(Ca) and IK(Ca) on EDHF-mediated relaxation of human omental and myometrial arteries preconstricted with either arginine vasopressin or U46619. Human arteries were isolated from omental and myometrial biopsies taken from healthy women undergoing planned cesarean section at term. Endothelial function was assessed using wire myography. In all vessels examined, nonspecific blockade of IK(Ca) with charybdotoxin attenuated EDHF-attributed relaxation. However, when Tram 34 was used to block IK(Ca), the attenuation of relaxation was evident only with U46619 preconstriction. In arteries from both vascular beds, and with either preconstrictor, a combination of either apamin and charybdotoxin or apamin plus Tram 34 almost ablated EDHF-attributable relaxation. These data support the notion that in human systemic arteries, activation of, primarily, SK(Ca) and IK(Ca)K(+) channel subtypes underlies EDHF-mediated relaxation. These results have important implications for future studies ascertaining the molecular mechanisms of hypertensive disorders (eg, preeclampsia, in which EDHF is thought to be aberrant).

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Abnormal karyotype was more common when CDH was associated with other anomalies. In multivariate analysis, lower birthweight and prenatal diagnosis had a significant impact on survival. Only prenatally diagnosed CDH survival figures should be utilised in prenatal counselling.

BackgroundWomen presenting with reduced fetal movements (RFM) in the third trimester are at increased risk of stillbirth or fetal growth restriction. These outcomes after RFM are related to smaller fetal size on ultrasound scan, oligohydramnios and lower human placental lactogen (hPL) in maternal serum. We performed this study to address whether a randomised controlled trial (RCT) of the management of RFM was feasible with regard to: i) maternal recruitment and retention ii) patient acceptability, iii) adherence to protocol. Additionally, we aimed to confirm the prevalence of poor perinatal outcomes defined as: stillbirth, birthweight <10th centile, umbilical arterial pH <7.1 or unexpected admission to the neonatal intensive care unit.MethodsWomen with RFM ≥36 weeks gestation were invited to participate in a RCT comparing standard management (ultrasound scan if indicated, induction of labour (IOL) based on consultant decision) with intensive management (ultrasound scan, maternal serum hPL, IOL if either result was abnormal). Anxiety was assessed by state-trait anxiety index (STAI) before and after investigations for RFM. Rates of protocol compliance and IOL for RFM were calculated. Participant views were assessed by questionnaires.Results137 women were approached, 120 (88%) participated, 60 in each group, 2 women in the standard group did not complete the study. 20% of participants had a poor perinatal outcome. All women in the intensive group had ultrasound assessment of fetal size and liquor volume vs. 97% in the standard group. 50% of the intensive group had IOL for abnormal scan or low hPL after RFM vs. 26% of controls (p < 0.01). STAI reduced for all women after investigations, but this reduction was greater in the standard group (p = 0.02). Participants had positive views about their involvement in the study.ConclusionAn RCT of management of RFM is feasible with a low rate of attrition. Investigations decrease maternal anxiety. Participants in the intensive group were more likely to have IOL for RFM. Further work is required to determine the likely level of intervention in the standard care arm in multiple centres, to develop additional placental biomarkers and to confirm that the composite outcome is valid.Trial registrationISRCTN07944306