title: The Recovery Time of Myometrial Responsiveness After Oxytocin-Induced Desensitization in Human Myometrium In Vitro.
abstract: BACKGROUND
  Postpartum hemorrhage secondary to uterine atony is a leading cause of maternal morbidity. Prolonged exposure to oxytocin for labor augmentation can result in the desensitization phenomenon, a decrease in the responsiveness of myometrium to further oxytocin. It is currently not known whether waiting for a specific time interval after the cessation of oxytocin allows the oxytocin receptors to resensitize and recover, thereby improving subsequent oxytocin-induced myometrial contractility. We aimed to investigate the effect of a rest period of 30, 60, and 90 minutes after oxytocin administration on the recovery of oxytocin-desensitized human myometrium in vitro. We hypothesized that the longer the rest period, the better the responsiveness and subsequent oxytocin-induced contractility of the myometrium.
  
  
  METHODS
  Myometrial tissue was obtained from women undergoing elective cesarean deliveries. The myometrial sample was dissected into 4 strips, and each strip was mounted in a single organ bath with physiological salt solution (PSS) under homeostatic conditions and then pretreated for 2 hours with oxytocin 10 M. After pretreatment, each strip was washed with PSS and allowed to rest in PSS solution for 30, 60, or 90 minutes. At the end of the rest period, dose-response testing to oxytocin 10 to 10 M was performed. A control group consisted of oxytocin dose-response testing without any oxytocin pretreatment. Contractile parameters were measured and compared among the groups after square root transformation. The primary outcome was motility index (frequency × amplitude), and secondary outcomes included frequency, amplitude, and area under the curve.
  
  
  RESULTS
  Fifty-five experiments were conducted from samples obtained from 16 women. The mean motility index (√g·contractions/10 min) during the dose-response curve (oxytocin 10 to 10 M) in the control group was significantly greater than all the experimental groups; the mean estimated differences (95% confidence intervals) were -1.33 (-2.50 to -0.15, P = 0.02), -1.59 (-2.68 to -0.50, P = 0.004), and -1.88 (-2.97 to -0.80, P = 0.001) for the 30-, 60-, and 90-minute groups, respectively. When the experimental groups were compared, there were no significant differences in any of the contractility parameters; however, confidence intervals were wide.
  
  
  CONCLUSIONS
  Our study shows that oxytocin pretreatment attenuates oxytocin-induced contractility in human myometrium despite a rest period of up to 90 minutes after oxytocin administration. However, we were unable to determine whether increasing the rest period from 30 to 90 minutes results in improvement in myometrial contractility because of our small sample size relative to the variability in the contractile parameters. Further laboratory and clinical in vivo studies are necessary to determine whether a rest period up to 90 minutes results in improvement in myometrial contractility. In addition, further experimental studies are necessary to determine the key mechanisms of oxytocin receptor resensitization.
authors.affiliation: From the *Department of Anesthesia and Pain Management, Mount Sinai Hospital, University of Toronto, Toronto, Canada; and †Department of Anesthesia and Pain Management, Mount Sinai Hospital, University of Toronto, Toronto, Canada.
authors.forename: Mrinalini
authors.initials: M
authors.lastname: Balki
authors.forename: Nivetha
authors.initials: N
authors.lastname: Ramachandran
authors.forename: Sang
authors.initials: S
authors.lastname: Lee
authors.forename: Chiraag
authors.initials: C
authors.lastname: Talati
mesh_terms: D000328:Adult; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D009215:Myometrium / Q000187:drug effects* / Q000378:metabolism; D010120:Oxytocics / Q000494:pharmacology*; D010121:Oxytocin / Q000494:pharmacology*; D011247:Pregnancy; D011446:Prospective Studies; D018045:Receptors, Oxytocin / Q000819:agonists / Q000378:metabolism; D020127:Recovery of Function; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014590:Uterine Contraction / Q000187:drug effects*
chemical_list: C569600:OXTR protein, human; D010120:Oxytocics; D018045:Receptors, Oxytocin; D010121:Oxytocin