Effect of Magnesium Sulphate Pre-exposure on Oxytocin-induced Contractility in Desensitized Human Myometrium - an in Vitro Study
Condition: Postpartum Hemorrhage
MeSH terms: Postpartum Hemorrhage; Hemorrhage
Study type: Interventional

Summary: 
      Postpartum hemorrhage (PPH) is the loss of more than 500ml of blood within 24 hours after
      delivery. It is a major cause of maternal morbidity and mortality across the globe.

      Oxytocin is a naturally-occurring hormone that causes the uterus to contract, thereby causing
      labor. A synthetic form of oxytocin is used in obstetric medicine in the same way. It causes
      the uterus to contract by acting at the oxytocin receptor (OTR). It is used for both the
      prevention and the treatment of PPH. By causing the uterus to contract, it constricts the
      blood vessels within it, thus reducing bleeding.

      Oxytocin is also used to augment labor in women with slow labor progression. Desensitization
      of the OTR after prolonged exposure to oxytocin occurs, leading to reduced contractions of
      the uterus with the same doses of oxytocin. This has been demonstrated in previous studies
      done by the investigators. The resultant need for a higher oxytocin dose to cause adequate
      uterine contraction has also been demonstrated in laboring women having received oxytocin for
      labor augmentation.

      Magnesium sulphate (MgSO4) is widely used within obstetric medicine. It is used for seizure
      prevention and treatment in preeclampsia and eclampsia, and is used for fetal neuroprotection
      in preterm labor, to reduce the risk of cerebral palsy. It is well-known to have a relaxant
      effect on uterine muscle, and as such, has been used as a tocolytic agent in preterm labour
      to prevent premature contractions and premature delivery. The effect of MgSO4 on contractions
      in oxytocin pre-treated myometrium has not been fully elucidated with human lab studies.
      There are suggestions it may lead to increased oxytocin requirements or increased postpartum
      hemorrhage (PPH) in preeclamptic patients. This bears significance in the preeclamptic and
      eclamptic populations who are likely to be receiving MgSO4 in combination with oxytocin.

      The investigators hypothesize that MgSO4 will reduce uterine contractions in oxytocin
      pre-treated myometrium, as well as untreated myometrium, and higher oxytocin doses will be
      needed to produce equivalent contractions. This will help us to better understand the
      implications of the use of these drugs together in the clinical setting.
    

Detailed description: 
      MgSO4 is known to cause relaxation of uterine muscle in the doses used for preeclampsia and
      eclampsia and fetal neuroprotection. In these clinical settings, after delivery, oxytocin is
      often given to prevent or treat PPH. There is evidence that patients with preeclampsia
      already have a higher risk of PPH than non-preeclamptic patients. In the presence of the
      effects of MgSO4 treatment on the uterus, PPH could be worse in theory. If patients have had
      oxytocin-augmented labor, then the desensitization effect on the uterus also comes into play.
      Performing this study in vitro will allow us to assess the effects on the uterine muscle of
      MgSO4 in oxytocin-desensitized tissue samples.

      Scientific evidence on pregnancy outcomes in these patients is timely and important. A study
      of myometrial contractility under controlled conditions is likely to provide us with
      information on the interactions between oxytocin and MgSO4 that occurs in many clinical
      scenarios, eliminating any confounders that could be encountered in clinical settings. The
      investigators hope to determine the myometrial contraction patterns induced by oxytocin in
      the presence of MgSO4, including in myometrial specimens pre-treated with oxytocin plus
      MgSO4, to mimic the clinical scenarios in preeclampsia and fetal neuroprotection. This will
      expand the depth of our understanding of the desensitization phenomenon, and could provide
      valuable insight into the mechanism responsible for PPH in these patient populations. This
      study will form a basis for future modifications in oxytocin augmentation regimens and
      pharmacotherapy for control of uterine atony and PPH in these patient populations being
      simultaneously treated with MgSO4.
    

Intervention name(s): Oxytocin; Magnesium Sulphate
Intervention type(s): Drug; Drug
Intervention description(s): Oxytocin, 10-5M solution; Magnesium sulphate, 3.5mM solution
Other intervention name(s): pitocin
Intervention MeSH terms: Magnesium Sulfate; Oxytocin
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Uterine contraction; Oxytocin; Magnesium sulphate