In Vitro Optimization of Oxytocin-induced Myometrial Contractility by Propranolol - Potential Applications in Induction of Labour and Treatment of Postpartum Hemorrhage
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 57
- 试验地点
- 1
- 主要终点
- Motility index
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 16 Years 至 40 Years（Child, Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Patients who give written consent to participate in this study
- •Patients with gestational age 37-41 weeks
- •Non-laboring patients, not exposed to exogenous oxytocin
- •Patients requiring primary Cesarean delivery or first repeat Cesarean delivery
排除标准
- •Patients who refuse to give written informed consent
- •Patients who require general anesthesia
- •Patients who had previous uterine surgery or more than one previous Cesarean delivery
- •Patients with any condition predisposing to uterine atony and postpartum hemorrhage, such as abnormal placentation, multiple gestation, preeclampsia, macrosomia, polyhydramnios, uterine fibroids, bleeding diathesis, chorioamnionitis, or a previous history of postpartum bleeding
- •Emergency Cesarean section in labor
- •Patients on medications that could affect myometrial contractility, such as nifedipine, labetolol or magnesium sulfate
研究组 & 干预措施
Low Dose Oxytocin
The myometrial samples are bathed in an oxytocin solution at increasing concentrations (from 10 -12M to 10 -9M)
干预措施: Oxytocin (Drug)
Propranolol
The myometrial samples are bathed in a propranol solution at 10 -6M
干预措施: Propranolol (Drug)
Propranolol + low dose oxytocin
The myometrial samples are bathed in an oxytocin solution at increasing concentrations (from 10 -12M to 10 -9M) plus propranol (10 -6M)
干预措施: Oxytocin (Drug)
Propranolol + low dose oxytocin
The myometrial samples are bathed in an oxytocin solution at increasing concentrations (from 10 -12M to 10 -9M) plus propranol (10 -6M)
干预措施: Propranolol (Drug)
High Dose Oxytocin
The myometrial samples are bathed in an oxytocin solution (10 -5M), followed by increasing concentrations of oxytocin (from 10 -8M to 10 -5M)
干预措施: Oxytocin (Drug)
High Dose Oxytocin, Propranolol-pretreated
The myometrial samples are bathed in an oxytocin solution (10 -5M) plus propranolol (10 -6M), followed by increasing concentrations of oxytocin (from 10 -8M to 10 -5M)
干预措施: Oxytocin (Drug)
High Dose Oxytocin, Propranolol-pretreated
The myometrial samples are bathed in an oxytocin solution (10 -5M) plus propranolol (10 -6M), followed by increasing concentrations of oxytocin (from 10 -8M to 10 -5M)
干预措施: Propranolol (Drug)
High dose oxytocin + propranolol
The myometrial samples are bathed in an oxytocin solution (10 -5M), followed by increasing concentrations of oxytocin (from 10 -8M to 10 -5M) plus propranolol (10 -6M)
干预措施: Oxytocin (Drug)
High dose oxytocin + propranolol
The myometrial samples are bathed in an oxytocin solution (10 -5M), followed by increasing concentrations of oxytocin (from 10 -8M to 10 -5M) plus propranolol (10 -6M)
干预措施: Propranolol (Drug)
结局指标
主要结局
Motility index
时间窗: 3 hours
Motility index (MI) takes into account both the amplitude and frequency of the myometrial contraction. It is a calculated outcome, based on the formula: frequency/(10 x amplitude). The analysis is undertaken by attaching myometrial strips between an isometric force transducer and the base of an organ bath chamber.
次要结局
- Integrated area under response curve (AUC)(3 hours)
- Amplitude of contraction(3 hours)
- Frequency of contraction(3 hours)