The Effects of Nitroglycerin on the Oxytocin Dose–Response Profile in Oxytocin-Desensitized and Naïve Human Myometrium: An In Vitro Study
Authors: Jayasooriya Gayani S. , Carvalho Jose C. A. , Luca Alice , Balki Mrinalini 
Published: August 2020

Background:
Nitroglycerin is used for acute reduction in uterine tone. Prolonged oxytocin exposure causes desensitization of oxytocin receptors. It is unknown if nitroglycerin exposure impacts the subsequent action of oxytocin in the setting of oxytocin receptor desensitization. This study investigated the effects of nitroglycerin on oxytocin-desensitized and oxytocin-naïve human myometrium and the subsequent response to oxytocin dose–response testing in vitro.

METHODS:
Myometrial samples from 17 elective cesarean deliveries were divided into strips and allocated to 1 of 4 groups: (1) oxytocin desensitized and no nitroglycerin; (2) oxytocin desensitized and nitroglycerin; (3) oxytocin naïve and nitroglycerin; and (4) oxytocin naïve and no nitroglycerin. Final analysis included 28 strips per group. Nitroglycerin groups were exposed to incremental concentrations of nitroglycerin, while no nitroglycerin groups were kept in control (physiological salt) solution. All groups then underwent oxytocin dose–response testing. Primary outcome was motility index (amplitude × frequency; grams × contractions per 10 minutes [g·c/10 min]). Secondary outcomes were amplitude (g), frequency (contractions/10 minutes), and area under the curve (g·s). All outcomes (nitroglycerin and oxytocin dose–response periods) were expressed as a percentage change from baseline. Values were log transformed, compared using regression modeling and reported as the ratio of 2 geometric means (relative difference).

RESULTS:
No significant difference was observed in motility index following nitroglycerin administration in oxytocin-desensitized versus oxytocin-naïve groups (relative difference = 19.0%; 95% confidence interval [CI], −32.6 to 109.9; P = .55). On oxytocin dose–response testing, motility index was highest in oxytocin-naïve and no nitroglycerin samples (group 4) (1.356 g·c/10 minutes) followed by oxytocin-naïve and nitroglycerin (group 3) (0.882 g·c/10 minutes), oxytocin-desensitized and no nitroglycerin (group 1) (0.769 g·c/10 minutes), and oxytocin-desensitized and nitroglycerin (group 2) (0.651 g·c/10 minutes) samples. Motility index was significantly reduced in group 1 vs 4 (relative difference = −43.3%; 95% CI, −66.5 to −4.1; P = .034) and group 2 vs 4 (relative difference = −52.0%; 95% CI, −70.9 to −20.8; P = .004). While in groups 3 vs 4, both amplitude (relative difference = −17.8%; 95% CI, −30.9 to −2.2; P = .27) and area under the curve (AUC; relative difference = −17.5%; 95% CI, −30.7 to −1.8; P = .030) were reduced.

CONCLUSIONS:
Nitroglycerin-induced relaxation was not different between oxytocin-desensitized and oxytocin-naïve human myometrial strips in vitro. However, oxytocin-induced contractility was attenuated after nitroglycerin exposure in both oxytocin-desensitized and oxytocin-naïve samples, with maximum attenuation observed in desensitized tissues. This finding warrants further clinical studies to explore uterine responsiveness to oxytocin in women with oxytocin-augmented labors after nitroglycerin administration.