Abstract
BackgroundWomen at risk of preterm delivery receive magnesium sulfate (MgSO4) in the pre-delivery phase to reduce their child’s risk of neurodevelopmental complications associated with preterm birth. However, the mechanisms underpinning its placental vascular role remain uncertain.MethodsThe aim of this study was to examine MgSO4 action on vascular tone in male and female human placental vessels from term and preterm deliveries. Vessels were obtained from placental biopsy following birth at term (37–41 weeks) or preterm gestation (<36 weeks of gestation). The vessels were mounted on a pressure myograph, pre-constricted with synthetic endoperoxide prostaglandin PGH2 (U46619) (0.1–100 μmol/l), and percentage of relaxation was calculated following incubation with bradykinin. Experiments were carried out in the presence of MgSO4 (0.2 mmol/l), NΨ-nitro-L-arginine methyl ester (L-NAME) (0.1 mmol/l), indomethacin (10 μmol/l), Ca2+-activated K+ channel blocker TRAM-34 (1 μM) and apamin (3 μM) to assess mechanisms of vascular function. Vascular [calcium ions (Ca2+)] was analysed using a colorimetric calcium assay.ResultsVasodilation in vessels from preterm males was significantly blunted in the presence of MgSO4 when compared to preterm female and term male and female vessels. Overall, MgSO4 was observed to differentially modulate placental vascular tone and vascular calcium concentrations in a sex-specific manner.ConclusionsAs MgSO4 regulates human placental blood flow via specific pathways, foetal sex-specific MgSO4 treatment regimes may be necessary. In an era of increasing awareness of individualised medicine, sex-specific effects may be of importance when developing strategies to optimise care in high-risk patients.
Highlights
Women at risk of preterm delivery receive magnesium sulfate (MgSO4) in the pre-delivery phase to reduce their child’s risk of neurodevelopmental complications associated with preterm birth
No further differences were observed at magnesium sulphate (MgSO4) concentrations of 0.25 mmol/l as all vessels across all groups appeared to reach the point of saturation with further doses having no effect on percentage of relaxation (Fig. 2)
MgSO4 is likely to alter the efficacy of calcium to maintain a ‘normal’ maximum tension or vasodilation when applied to vascular smooth muscle by reducing the translocation of calcium into smooth muscle. Corroboratory evidence for this comes from our demonstration of a consistently higher vascular [Ca2+]i in male preterm vessels when compared to female preterm placental chorionic plate vessels following incubation with MgSO4. This suggests that MgSO4 has a role in preventing free calcium uptake into the smooth muscle of these vessels, reducing basal vascular tone and promoting vasodilation
Summary
Women at risk of preterm delivery receive magnesium sulfate (MgSO4) in the pre-delivery phase to reduce their child’s risk of neurodevelopmental complications associated with preterm birth. In an effort to reduce CP risk in children born prematurely, obstetric practice includes treatment with intravenous magnesium sulphate (MgSO4) for women at high risk of delivery before 30 weeks gestation [9]. While the overall efficacy of this approach has been well described, the number of women that needed treatment to prevent one case of CP is relatively high [10]. This suggests that MgSO4 either has an indirect role in the prevention of CP or that its
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