The Relaxant Effect of Nitroglycerin on Oxytocin Desensitized Human Myometrium
Condition: Postpartum Hemorrhage
MeSH terms: Postpartum Hemorrhage; Hemorrhage
Study type: Interventional

Summary: 
      Oxytocin causes myometrial contraction via the oxytocin receptor (OTR). Desensitization of
      the OTR after exposure to oxytocin has been demonstrated in previous studies. The resultant
      need for a higher oxytocin dose to cause adequate uterine contraction in vivo has also been
      demonstrated in laboring women having received oxytocin for labor augmentation.

      Achieving rapid uterine relaxation can be invaluable for maternal and fetal wellbeing in some
      acute obstetric emergency settings. Nitroglycerin has become a commonly used agent for
      achieving rapid uterine relaxation amongst obstetric anesthesiologists.

      Previous studies have concluded that oxytocin can be used to re-establish uterine tone
      following nitroglycerin mediated relaxation. However, no studies to date have looked at the
      effects of nitroglycerin mediated relaxation of uterine muscle that has undergone oxytocin
      receptor desensitization. Nor has the response to oxytocin re-exposure and return of
      contractility in desensitized myometrium (following nitroglycerin) been examined.

      The investigators hypothesize that nitroglycerin will reduce and inhibit uterine contractions
      in both oxytocin pre-treated myometrium, as well as untreated myometrium in a dose dependent
      fashion, but that myometrium that has undergone OTR desensitization will require less
      nitroglycerin for contractions to abate.

      The investigators also expect that the dose of oxytocin required to re-establish equivalent
      contractions will be higher in the myometrial samples which have undergone nitroglycerin
      mediated relaxation.
    

Detailed description: 
      Oxytocin and nitroglycerin have opposing actions on the myometrium. The pharmacological
      properties of quick onset and offset of action of nitroglycerin have made this the preferred
      drug to be used in acute scenarios where uterine relaxation is necessary.

      As nitroglycerin causes changes to intracellular calcium levels and the ability uterine
      muscle to engage in effective contraction, it is plausible that the effects of nitroglycerin
      may interfere with subsequent uterine contractility and action of oxytocin.

      The situation where a difficult fetal extraction is encountered at cesarean section may be in
      two broad groups of patients. Those pre-exposed to oxytocin and those with an oxytocin naïve
      myometrium. Given the large observational variation in dosages of nitroglycerin usage seen in
      the literature we feel it is vital to investigate whether pre-exposure to oxytocin impacts on
      the ability of nitroglycerin to relax uterine smooth muscle. Furthermore, once the uterus has
      relaxed following nitroglycerin exposure, is there a need for higher doses of oxytocin to be
      administered in order to re-engage the uterus in effective contraction? And is this
      requirement further exacerbated by the phenomenon of oxytocin receptor desensitization? These
      clinically important questions will be addressed by the design of this in vitro myometrial
      study.
    

Intervention name(s): Oxytocin; Nitroglycerin
Intervention type(s): Drug; Drug
Intervention description(s): Oxytocin 10-5M solution; Nitroglycerin 25-1000mcg
Other intervention name(s): Duratocin, pitocin
Intervention MeSH terms: Nitroglycerin; Oxytocin
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Uterine contraction; Oxytocin; Nitroglycerin