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The effect of nitroglycerin on oxytocin naïve and desensitized human myometrium– an in vitro study
Abstract Number: S3A-5
Abstract Type: Original Research
Introduction: Nitroglycerin (NTG) is used for acute reduction in uterine tone. Prolonged oxytocin (OT) exposure causes desensitization of OT receptors,resulting in subsequent uterine atony. Many women requiring acute tocolysis at cesarean delivery are pre-exposed to OT during labor, however, no studies to date have examined the effects of NTG on desensitized uterine muscle. We investigated the relaxant effect of NTG on OT desensitized human myometrium and the subsequent return of oxytocin-induced contractility in-vitro.
Methods: Following written informed consent from patients undergoing elective cesarean deliveries, this in-vitro study was undertaken using myometrium dissected into 8 strips. Each strip was mounted in a single organ bath and equilibrated with physiological salt solution (PSS) and allocated to one of 4 groups: G1)OT Naïve + No NTG (Control); G2)OT Desensitized + No NTG; G3)OT Naïve + NTG; G4)OT Desensitized + NTG. Desensitized and OT Naïve groups were pretreated with OT 10-5M and PSS, respectively, for 2 hours. This was followed by cumulative administration of NTG 25, 50, 100 and 500μM. All groups then underwent dose-response to OT 10-10M to 10-5M. Primary outcome was motility index (MI=frequency x amplitude) expressed as a multiple of baseline(equilibration)MI(1.0).
Results: A total of 46 experiments have been conducted (G1=11, G2=13, G3=10, G4=12). No significant difference was found in MI on incremental NTG exposure in OT desensitized vs OT naïve groups (p=0.2)[Fig 1]. All contractions in samples stopped by 500μM NTG exposure. A significant reduction in mean (SD) MI was found on OT dose-response testing when OT desensitized myometrium had been exposed to NTG [1.1 (0.9)], compared to samples not exposed to NTG [4.85 (5.3)] (p=0.025). Comparisons between mean MI of other groups were not statistically significant.
Discussion: Human myometrium relaxes similarly in response to NTG, irrespective of OT desensitization. Subsequent OT induced contractile response appears to be attenuated after NTG exposure, particularly in myometrium where OT desensitization has occurred. These results suggest that NTG administration after OT exposure in labor may result in higher OT (or additional uterotonic) requirement for return of uterine tone compared to oxytocin naïve myometrium exposed to NTG. This may have implications in the risk of postpartum hemorrhage.
1. J Obstet Gynaecol Can.2002:24;403-9