The Impact of Pregnancy and Pregnancy-associated Hypertension on Human Uterine Myometrial Artery Reactivity

NCT03888170 | Withdrawn DMC

• 1 other identifier: 1902347880
• Study Type: observational
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The investigators seek to describe the composition, architecture, and electrical conduction properties of the human uterine myometrial artery and their impact on vascular reactivity upon exposure to hypertensive stress. Non-pregnant women and pregnant women with and without hypertensive complications will be studied to evaluate the influence of these states on the myometrial arteries. Vascular over-reactivity and disruption of the normal pregnancy-associated physiologic changes of relaxed vascular tone possess the potential for non-compensated blood flow to the uterus and placenta that is insufficient to meet the metabolic demands of a growing placenta. With an understanding of these changes, the research team will be able to propose basic mechanistic changes of pathologic myogenic tone that may ultimately be investigated as potentially modifiable processes to reduce the development and/or severity of these pregnancy complications (gestational hypertension, preeclampsia, eclampsia, small for gestational age, intrauterine growth restriction and intrauterine fetal demise. ).

Conditions

Pregnancy; Preeclampsia; Hypertension in Pregnancy

Keywords

Myogenic Tone; Vascular Reactivity; Vascular Remodeling

Outcome Measures

Primary Outcomes (1)

• Pressure-induced vasoconstriction of human uterine myometrial arteries [% constriction = ((passive vessel diameter - active vessels diameter) / passive diameter) X 100]

  Pressure-induced constrictions (PIC) are expressed as a percent decrease of the fully dilated diameter of individual arteries at the same intravascular pressure. Diameter values will be analyzed as percent constriction. The passive diameter of the artery is measured in calcium-free physiologic saline solution containing 80 µM diltiazem. In turn, the active diameter of the myometrial artery is measured in response to calcium-containing physiologic saline solution. Both measurements will be obtained and measured across a physiologic range of blood pressures.

  Pressure-induced vasoconstriction will be assessed immediately following specimen acquisition and dissection to isolate the artery of interest. This occurs as a single time point of measurement, less than 24 hours following specimen acquisition.

Secondary Outcomes (3)

• Changes in pressure-induced vasoconstriction in response to blockade of voltage-dependent potassium channels.

  Pressure-induced vasoconstriction will be assessed immediately following specimen acquisition and dissection to isolate the artery of interest. This occurs as a single time point of measurement, less than 24 hours following specimen acquisition.

• Changes in pressure-induced vasoconstriction in response to blockade of prostaglandin production.

  Pressure-induced vasoconstriction will be assessed immediately following specimen acquisition and dissection to isolate the artery of interest. This occurs as a single time point of measurement, less than 24 hours following specimen acquisition.

• Changes in pressure-induced vasoconstriction in response to blockade of nitric oxide synthase.

  Pressure-induced vasoconstriction will be assessed immediately following specimen acquisition and dissection to isolate the artery of interest. This occurs as a single time point of measurement, less than 24 hours following specimen acquisition.

Study Arms (3)

Non-pregnant

Women aged 18-45 years old undergoing elective hysterectomy (either vaginal, laparoscopic, or open routes) for benign indications.

Other: No intervention

Pregnant

Pregnant women aged 18-45 undergoing cesarean section at or beyond 34 weeks gestational age.

Other: No intervention

Pregnant with hypertension

Pregnant women aged 18-45 undergoing cesarean section at or beyond 34 weeks gestational age with pregnancy complicate by chronic hypertension, gestational hypertension, preeclampsia without severe features, preeclampsia with severe features, or superimposed preeclampsia.

Other: No intervention

Interventions

No intervention OTHER

No intervention

Non-pregnant; Pregnant; Pregnant with hypertension

Eligibility Criteria

• Age: 18 Years - 45 Years
• Gender Eligibility Details: Pregnancy
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Patients eligible for inclusion in this study protocol will be aged 18 years-old and older, all of which will be female. Additionally, study subjects may or may not be pregnant. There will be no restrictions based on race or ethnic group.

You may qualify if:

• Women aged 18-45 years old
• Non-pregnant women undergoing elective hysterectomy (either vaginal, laparoscopic, or open routes) for benign indications.
• Pregnant women undergoing cesarean section at early-term and beyond (\> 34 weeks)

You may not qualify if:

• Pregnancy \< 34 weeks gestation.
• Non-English speaking
• Cesarean section performed with non-low transverse hysterotomy.
• History of uterine rupture or cesarean scar dehiscence, currently pregnant.
• Uterine window or significant myometrial thinning appreciated at time of surgery.
• Hysterectomy performed for treatment of malignancy
• Hysterectomy performed for risk-reduction purposes in setting of genetic predisposition to gynecologic cancer
• Diagnosis of infectious disease and/or blood borne illness
• Learning or developmental disability that precludes appropriate consenting procedures

Sponsors & Collaborators

• University of Arizona: lead
• Midwestern University: collaborator

Biospecimen

Retention: SAMPLES WITHOUT DNA

1. Blood Draw - venous blood samples will be collected from all patients for measurement of circulating hormone and inflammatory marker levels. 2. Tissue/Amniotic Fluid Collection 1. Samples from Cesarean section: amniotic fluid specimen, fetal membranes and placental biopsy, and a full-thickness uterine biopsy. 2. Myometrial samples from elective hysterectomy: full-thickness uterine biopsy.

MeSH Terms

Conditions

Pre-Eclampsia; Hypertension, Pregnancy-Induced; Vascular Remodeling

Condition Hierarchy (Ancestors)

Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Pathologic Processes

Study Officials

• Michael P Leovic, MD

  University of Arizona

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2019
• First Posted: March 25, 2019
• Study Start: April 1, 2019
• Primary Completion: April 1, 2020
• Study Completion: July 1, 2020
• Last Updated: December 18, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share