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Investigating the effect of extracellular calcium on contractility, in oxytocin induced desensitized human myometrium in-vitro
Abstract Number: O1-02
Abstract Type: Original Research
Introduction: A significant risk factor for uterine atony is prolonged exposure to oxytocin for augmentation of labor, resulting in the 'desensitization' phenomenon, a decreased response of the myometrium to further oxytocin . The importance of calcium is well-established in myometrial contractility , however, in the context of desensitized myometrium, its significance is unknown. We investigated the effect of low, normal and high calcium concentration on oxytocin-induced contractility, in desensitized human myometrium in-vitro.
Methods: Myometrial tissue, from patients undergoing elective cesarean deliveries, was dissected into 6 strips. Each strip was mounted in an organ bath with physiological salt solution (PSS) and then pretreated for 2-hours with either oxytocin 10-5M (to achieve myometrial desensitization ), or no oxytocin (control). The tissue was washed with PSS, and the calcium concentration altered to reflect low (1.25mM), normal (2.5mM) or high (3.75mM) levels, providing 6 groups. Thereafter, a dose-response to oxytocin 10-10M to 10-5M was performed. Contractile parameters were measured. The primary outcome was motility index (MI, frequency x amplitude). Analysis will be undertaken with linear regression models adjusted for repeated measures through compound symmetry covariance structure.
Results: 49 experiments (of a total of 192) have been analyzed. The control experiments show an increase in MI from baseline when analyzed as a cumulative dose-response average, in the presence of 2.5mM calcium (538%), vs 1.25mM (465%) and 3.75mM (341%). Similarly, the desensitized groups showed higher MI in the presence of 2.5mM calcium (462%), vs 1.25mM (460%) and 3.75mM (173%) (Fig.1). Following further recruitment of 17 patients (providing 101 experiments, at a rate of 18/week), the study will complete by March 2015.
Discussion: The results so far show that in both desensitized and non-desensitized myometrium, calcium at physiological levels provides superior contractility, while hypercalcemia markedly attenuates contractility. Thus, after prolonged exposure to continuous oxytocin in labor augmentation, uterine atony and PPH could be attenuated by promoting normocalcemia and preventing hypo- or hypercalcemia. Final discussion will be presented at the meeting.
1) Am J Obstet Gynecol 2003;188:497-502
2) Biol Reprod 1989;40:942-8
3) Anesthesiology 2013;119:552-61