title: The combination tocolytic effect of magnesium sulfate and an oxytocin receptor antagonist in myometrium from singleton and twin pregnancies.
abstract: BACKGROUND
  Preterm birth at <37 weeks of gestation is the most common and costly complication of pregnancy and remains the leading cause of neonatal morbidity, death, and reduced achievement in surviving infants. Magnesium sulfate is 1 class of tocolytics for threatened preterm labor; however, its clinical efficacy has been questioned. Twin pregnancies are at increased risk of preterm delivery compared with singleton gestations, which suggests that there is twin-specific risk to preterm delivery in twins. The prevention strategies that are applied to singleton pregnancies, however, have not been shown to be effective in twin pregnancies.
  
  
  OBJECTIVE
  The purpose of this study was to compare the relaxant effect of magnesium sulfate on spontaneous and oxytocin-augmented contractions of human myometrium from singleton and twin pregnancies and to examine whether the effect of oxytocin on magnesium sulfate's potency could be reversed with the use of the oxytocin receptor antagonist, atosiban.
  
  
  METHODS
  Myometrium was obtained at the time of prelabor cesarean section (36-40 weeks of gestation) from women with singleton (n=23) or twin (n=12) pregnancy. Isometric tension recordings were made on myometrial strips that were mounted in organ baths that were superfused with physiologic saline solution. Strips were exposed to rising concentrations of magnesium sulfate, and the effect on spontaneous contractions or stimulated with oxytocin (0.5 nmol/L) and in the presence or absence of atosiban (100 nmol/L) was recorded. The contractile characteristics after each application of magnesium sulfate, which included amplitude of contraction and activity integral, were measured. Concentration-response curves were fitted with the use of nonlinear regression and comparison of the negative logarithm of the 50% reduction in activity values.
  
  
  RESULTS
  Magnesium sulfate exerted an equal concentration-dependent inhibitory effect on spontaneous myometrial contractions from both singleton and twin myometrium (P>.05). The application of oxytocin produced a significant rightward shift in the concentration-response curves (P<.0001), but no differences were found between pregnancy groups (P>.05). The addition of atosiban shifted concentration-response curves significantly back to the left for amplitude of contraction and activity integral in singletons (P<.0001). However, only activity integral was significantly reversed in twins (P<.01).
  
  
  CONCLUSIONS
  Magnesium sulfate is equipotent in suppressing contractions in singleton and twin myometrium. Oxytocin (0.5 nmol/L) significantly reduces the tocolytic potency of magnesium sulfate, which may explain, in part, magnesium sulfate's poor efficacy in vivo; however, this can be reversed partially by the use of an oxytocin receptor antagonist. Combination tocolysis that involves oxytocin receptor antagonists requires further investigation.
authors.affiliation: Harris-Wellbeing Preterm Birth Research Centre, Department of Cellular and Molecular Physiology, the Institute of Translational Medicine, University of Liverpool, Liverpool, UK. Electronic address: s.arrowsmith@liverpool.ac.uk.
authors.forename: Sarah
authors.initials: S
authors.lastname: Arrowsmith
authors.affiliation: Department of Women's and Children's Health, the Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors.forename: James
authors.initials: J
authors.lastname: Neilson
authors.affiliation: Harris-Wellbeing Preterm Birth Research Centre, Department of Cellular and Molecular Physiology, the Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors.forename: Susan
authors.initials: S
authors.lastname: Wray
mesh_terms: D000328:Adult; D002585:Cesarean Section; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008278:Magnesium Sulfate / Q000494:pharmacology*; D009215:Myometrium / Q000187:drug effects*; D011247:Pregnancy; D059285:Pregnancy, Twin; D018045:Receptors, Oxytocin / Q000037:antagonists & inhibitors; D015149:Tocolytic Agents / Q000494:pharmacology*; D014590:Uterine Contraction / Q000187:drug effects*; D014668:Vasotocin / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D018045:Receptors, Oxytocin; D015149:Tocolytic Agents; C047046:atosiban; D008278:Magnesium Sulfate; D014668:Vasotocin
keywords: MgSO(4); atosiban; contraction; magnesium sulfate; myometrium; oxytocin; oxytocin receptor antagonist; pregnancy; tocolysis; twins