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Effect of magnesium sulfate on oxytocin-induced contractility in human myometrium: an in vitro study
Desire N Onwochei1, Jose C A Carvalho2,3, Alice Luca2
1Department of Anesthesia and Pain Management, Mount Sinai Hospital, University of Toronto, 600 University Avenue, Room 19-104, Toronto, ON, M5G 1X5, Canada. desire@doctors.org.uk.
Purpose:
The purpose of this study was to determine the contractile patterns induced by oxytocin in myometrium exposed to magnesium sulfate (MgSO4). We hypothesized that MgSO4 pretreatment would reduce oxytocin-induced myometrial contractions in both oxytocin-naïve and oxytocin-desensitized myometrium.
Methods:
In this prospective in vitro study, myometrial samples were obtained from 26 women undergoing elective Cesarean deliveries. Samples were divided into six groups. Four groups were apportioned to no pretreatment (control group), oxytocin 10-5 M pretreatment (desensitization group), MgSO4 3.5 mM pretreatment, and MgSO4 3.5 mM + oxytocin 10-5M pretreatment. This was followed by dose-response testing to oxytocin 10-10 to 10-5M in all four groups. Two additional groups included MgSO4 3.5 mM pretreatment and MgSO4 3.5 mM + oxytocin 10-5 M pretreatment, followed by dose-response testing to oxytocin along with MgSO4 3.5 mM. The outcomes were motility index (MI), as defined by the amplitude (g) × frequency of myometrial contractions (c) over ten minutes, and area under the curve (AUC).
Results:
In oxytocin-naïve myometrium, the mean (standard error [SE]) MI was not affected by MgSO4 pretreatment [3.31 (0.20) √g⋅c/10 min] as compared with control (P = 0.88), even when MgSO4 was continued during dose-response testing [2.50 (0.19) √g⋅c/10 min; P = 0.41]. In the oxytocin-desensitized model, mean (SE) MI was not affected by MgSO4 pretreatment [2.60 (0.21) √g⋅c/10 min; P = 0.68], but when MgSO4 was continued during the dose-response period, the MI was significantly reduced compared with control [1.89 (0.13) √g⋅c/10 min; P < 0.001]. The results for AUC were similar to MI, except for a significant reduction in oxytocin-naïve myometrium when MgSO4 was continued during dose-response testing (P = 0.02).
Conclusion:
Magnesium sulfate pretreatment does not impair oxytocin-induced myometrial contractility in oxytocin-naïve or desensitized myometrium unless it is continued during oxytocin dose-response testing. These results suggest that its tocolytic effect is likely dependent on an extracellular mechanism. The study was registered with ClinicalTrials.gov, number NCT02647268.