The Relaxant Effect of Nitroglycerin on Oxytocin Desensitized Human Myometrium

NCT03408054 | Completed

• 1 other identifier: 18-01
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

Oxytocin causes myometrial contraction via the oxytocin receptor (OTR). Desensitization of the OTR after exposure to oxytocin has been demonstrated in previous studies. The resultant need for a higher oxytocin dose to cause adequate uterine contraction in vivo has also been demonstrated in laboring women having received oxytocin for labor augmentation. Achieving rapid uterine relaxation can be invaluable for maternal and fetal wellbeing in some acute obstetric emergency settings. Nitroglycerin has become a commonly used agent for achieving rapid uterine relaxation amongst obstetric anesthesiologists. Previous studies have concluded that oxytocin can be used to re-establish uterine tone following nitroglycerin mediated relaxation. However, no studies to date have looked at the effects of nitroglycerin mediated relaxation of uterine muscle that has undergone oxytocin receptor desensitization. Nor has the response to oxytocin re-exposure and return of contractility in desensitized myometrium (following nitroglycerin) been examined. The investigators hypothesize that nitroglycerin will reduce and inhibit uterine contractions in both oxytocin pre-treated myometrium, as well as untreated myometrium in a dose dependent fashion, but that myometrium that has undergone OTR desensitization will require less nitroglycerin for contractions to abate. The investigators also expect that the dose of oxytocin required to re-establish equivalent contractions will be higher in the myometrial samples which have undergone nitroglycerin mediated relaxation.

Conditions

Postpartum Hemorrhage

Keywords

Uterine contraction; Oxytocin; Nitroglycerin

Outcome Measures

Primary Outcomes (1)

• Motility Index

  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.

  8 hours

Secondary Outcomes (3)

• Amplitude of contraction

  8 hours

• Frequency of contraction

  8 hours

• Integrated area under response curve (AUC)

  8 hours

Study Arms (4)

Control group

NO INTERVENTION

No oxytocin desensitization (pretreatment), no nitroglycerin

Oxytocin desensitized - no nitroglycerin

ACTIVE COMPARATOR

Pretreated with oxytocin, no nitroglycerin exposure

Drug: Oxytocin

Oxytocin desensitized - plus nitroglycerin

ACTIVE COMPARATOR

Pretreated with oxytocin followed by nitroglycerin exposure

Drug: Oxytocin; Drug: Nitroglycerin

Non oxytocin desensitized - plus nitroglycerin

ACTIVE COMPARATOR

No oxytocin pretreatment, followed by nitroglycerin exposure

Drug: Nitroglycerin

Interventions

Oxytocin DRUG

Oxytocin 10-5M solution

Also known as: Duratocin, pitocin

Oxytocin desensitized - no nitroglycerin; Oxytocin desensitized - plus nitroglycerin

Nitroglycerin DRUG

Nitroglycerin 25-1000mcg

Non oxytocin desensitized - plus nitroglycerin; Oxytocin desensitized - plus nitroglycerin

Eligibility Criteria

• Age: 16 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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 under spinal anesthesia

You may not qualify if:

• 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 with medical/pregnancy related conditions, such as diabetes, preeclampsia and essential hypertension

Sponsors & Collaborators

• Samuel Lunenfeld Research Institute, Mount Sinai Hospital: lead

Study Sites (1)

Mount Sinai Hospital

Toronto, Ontario, M5G1X5, Canada

Location

Related Publications (1)

• Jayasooriya GS, Carvalho JCA, Luca A, Balki M. The Effects of Nitroglycerin on the Oxytocin Dose-Response Profile in Oxytocin-Desensitized and Naive Human Myometrium: An In Vitro Study. Anesth Analg. 2021 Jan;132(1):231-239. doi: 10.1213/ANE.0000000000005055.

  PMID: 32858531 DERIVED

MeSH Terms

Conditions

Postpartum Hemorrhage

Interventions

Oxytocin; Nitroglycerin

Condition Hierarchy (Ancestors)

Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Puerperal Disorders; Uterine Hemorrhage; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Nitro Compounds; Organic Chemicals

Study Officials

• Mrinalini Balki, MD

  MOUNT SINAI HOSPITAL

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2018
• First Posted: January 23, 2018
• Study Start: January 3, 2018
• Primary Completion: April 13, 2018
• Study Completion: April 13, 2018
• Last Updated: February 22, 2019

Record last verified: 2019-02

Locations

CA (1)