Recovery of Oxytocin Responsiveness in Pregnant Human Myometrial Explants After Oxytocin-Induced Desensitization
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 oxytocin
      receptors (OTR) found on myometrial cells to cause uterine contraction.

      Women who require augmentation of labour with oxytocin because of inadequate labour
      progression are at increased risk of PPH because they have received intravenous oxytocin
      which exposes the uterus (and OTR) to doses greater than would normally be found without
      medical intervention. This exposure results in OTR desensitization and decreased uterine
      sensitivity to oxytocin which may lead to the use of much higher doses of oxytocin (up to 9x)
      or other agents for preventing and treating PPH with the potential for causing serious
      drug-related morbidity or fatality to the mother.

      Currently, in women who have failed labour augmentation and need to have a Cesarean delivery,
      it is not known if it would be beneficial to wait a certain period of time after
      discontinuing intravenous oxytocin before proceeding with the operation. The goal of the
      waiting time would be to allow the OTRs to recover and resensitize the uterus to the effects
      of oxytocin to avoid the need for high doses or additional uterus-contracting agents.

      Our hypothesis is that there will be a positive correlation between the magnitude of recovery
      of the myometrium's response to oxytocin and the time elapsed from the desensitizing oxytocin
      pretreatment (simulated labour augmentation).
    

Detailed description: 
      The investigators have previously established an in vitro model of labour augmentation and
      myometrial desensitization using pregnant human myometrium and an isometric tension recording
      device. The investigators propose to use this model in order to characterize the time course
      of recovery of oxytocin-desensitized myometrium to oxytocin sensitivity. These results will
      help in establishing whether myometrial recovery can occur within a clinically relevant time
      period, how much sensitivity is recovered, and the duration required.

      In the clinical setting of failed labour augmentation and OTR desensitization, it is not
      known if it is beneficial to wait a certain period of time after discontinuing intravenous
      oxytocin before proceeding to Cesarean section to allow for resensitization of the myometrium
      to oxytocin. The results of this study will provide insight into the time course of recovery
      of the myometrium using an in vitro model of failed labour augmentation. Based on the
      oxytocin dose-response curves after variable periods of time of "rest", the investigators
      will be able to determine the degree of recovery of myometrial contractility over time and
      whether this will occur in a clinically relevant time period for implementation into clinical
      practice.
    

Intervention name(s): Oxytocin
Intervention type(s): Drug
Intervention description(s): Oxytocin, 10-10mol/L to 10-5mol/L
Other intervention name(s): Pitocin
Intervention MeSH terms: Oxytocin
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Uterine contraction; Oxytocin receptors; Oxytocin desensitization