NCT03434444

In Vitro Optimization of Oxytocin-induced Myometrial Contractility by Propranolol

In Vitro Optimization of Oxytocin-induced Myometrial Contractility by Propranolol - Potential Applications in Induction of Labour and Treatment of Postpartum Hemorrhage

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 57 (actual)
• Sponsor: Samuel Lunenfeld Research Institute, Mount Sinai Hospital · Academic / Other
• Sex: Female
• Age: 16 Years – 40 Years
• Healthy volunteers: Accepted

Summary

The rates of cesarean deliveries (CD) and postpartum hemorrhage (PPH) are on the rise, with failed induction and augmentation of labor as major contributing factors. Oxytocin is commonly used for labor induction, as well as during the third stage of labor to minimize the risk of primary PPH. At delivery, it is imperative that the uterus responds effectively to parenteral oxytocin. Poor response to oxytocin following delivery is commonly due to prolonged labor with oxytocin augmentation that is known to "desensitize" the myometrium. Despite the option of several second line uterotonic agents, none of them are as effective as oxytocin in controlling PPH. Given that poor uterine muscle contraction is the root cause of both failed induction or augmentation (leading to a CD in labor) and uterine atony (leading to PPH), there is an urgent and clinically important need to investigate novel methods to enhance oxytocin-induced myometrial contractions. Propranolol, a beta adrenergic receptor agonist, has the potential to improve myometrial contractions by virtue of its ability to inhibit catecholamine production. The investigators plan to investigate the effects of propranolol in both naive and desensitized myometrium, in order to better understand its potential role in improving labor induction and reducing the risk of PPH following oxytocin exposure during labor. The investigators hypothesize that propranolol is likely to potentiate the action of oxytocin upon human myometrium, to ultimately help improve the success of labor induction/augmentation and treatment of PPH.

Detailed description

Myometrial samples will be used to investigate the effect of propranolol on uterine contractions when exposed to high and low doses of oxytocin (to simulate PPH treatment and labor induction respectively). The tissue will also be frozen at the end of the experiment, and Western blotting will be used to investigate the effect of propranolol on the expression patterns and cellular distribution of the oxytocin receptor and beta-adrenergic receptor and their signaling pathways in desensitized myometrium.

Conditions

• Postpartum Hemorrhage

Interventions

Type	Name	Description
DRUG	Oxytocin	Oxytocin in solution, ranging from 10 -12M to 10 -5M
DRUG	Propranolol	Propranolol in solution, 10-6M

Timeline

• Start date: 2017-09-08
• Primary completion: 2022-08-19
• Completion: 2022-08-20
• First posted: 2018-02-15
• Last updated: 2023-02-24

Locations

1 site across 1 country: Canada