Investigating the Effect of Extracellular Calcium on Oxytocin-induced Human Myometrial Contractility In-vitro
Condition: Postpartum Hemorrhage
MeSH terms: Postpartum Hemorrhage; Hemorrhage
Study type: Interventional

Summary: 
      Postpartum hemorrhage (PPH) is a leading cause of maternal morbidity and mortality worldwide
      and is caused most commonly by poor uterine muscle tone after delivery. The first line agent
      used in the prevention and treatment of PPH is oxytocin, which acts by binding with the
      oxytocin receptor (OTR) found on myometrial cells to cause uterine contraction. It does this
      by increasing levels of calcium within the myometrial cell, which promotes contraction. Women
      who require augmentation of labor with intravenous oxytocin because of inadequate labor
      progression have been shown to be at increased risk of PPH. In-vitro human myometrial models
      have shown that following prolonged exposure to oxytocin there is desensitization of the
      myometrium resulting in a significant reduction in contractility upon delivery of further
      oxytocin.

      Optimal levels of calcium are very important for contraction of the uterine muscle. Too
      little calcium results in a reduced contraction. Too much calcium may result in either
      stronger contractions, or even possibly relaxation of the muscle and therefore a reduced
      contraction. The investigators currently do not know the effects of calcium on the
      desensitized uterine muscle.

      The investigators hypothesize that myometrial contractility following desensitization of the
      myometrium would be reduced in myometrial samples exposed to low calcium, when compared to
      normal calcium or high calcium exposure. These results will help in establishing whether
      myometrial contraction can be augmented by increasing calcium levels within the body, or by
      optimizing normal physiological calcium levels, in the setting of a augmented prolonged
      labor, which is at higher risk of poor uterine contraction and PPH.
    

Detailed description: 
      The increased incidence of uterine atony and PPH following exogenous oxytocin administration
      during labor augmentation is related to myometrial OTR desensitization to oxytocin. Calcium
      is an important messenger required within the uterine muscle cell to result in muscle
      contraction following administration of oxytocin. A physiological level of calcium is known
      to provide optimal contractility to normal myometrium.

      Characterization of the importance of low, normal or high calcium levels in a setting of
      prolonged exogenous oxytocin administration may provide guidance for the use of exogenous
      calcium as a uterotonic adjunct; or for the optimization of serum calcium levels during
      augmented labor. In the clinical setting of failed labor augmentation and OTR
      desensitization, the role of serum calcium levels is not currently known.

      The investigators' previously validated in-vitro model provides a solid foundation for the
      study of myometrial contractility under controlled conditions, without any confounders that
      could be encountered in clinical settings.

      The results of this study will provide insight into the effect of low, normal or high calcium
      levels on the oxytocin pretreated (desensitized) and non-pretreated myometrium. Based on
      oxytocin dose-response curves after pretreatment to oxytocin and then subsequent exposure to
      either low, normal or high levels of calcium, the investigators will be able to determine the
      role of calcium on desensitized myometrium.
    

Intervention name(s): Oxytocin; Calcium
Intervention type(s): Drug; Drug
Intervention description(s): Experiments will be conducted with some myometrial strips pretreated with oxytocin, and others without any oxytocin pretreatment; Calcium will be applied to the myometrial strips in 3 concentrations; 1.25mM (low), 2.5mM (normal) and 5.0mM (high). Myometrial strips will be either oxytocin pretreated, or non-oxytocin pretreated.
Other intervention name(s): pitocin
Intervention MeSH terms: Oxytocin; Calcium
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Uterine contraction; Oxytocin desensitization