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

The experiments proposed here seek to identify mechanisms underlying changes in the human uterine myometrial artery reactivity during pregnancy. The first series of experiments will be to address the changes that have been observed in stress-strain relationships and arterial remodeling during pregnancy. The second series of experiments will address the endothelial dependency of augmented pregnancy-induced vasoconstriction in myometrial arteries during pregnancy. Finally, the third series of experiments will be to address the unique relationship between resting membrane potential, calcium (Ca2+) signaling, and vascular reactivity in myometrial arteries from non-pregnant and pregnant women.

Blood Draw Venous blood samples will be collected from all patients for measurement of circulating hormone and inflammatory marker levels, so that vascular reactivity changes related to these components can be appropriately controlled for so as to correctly characterize similar changes attributed to either pregnancy and/or exposure to hypertensive stress.

Tissue/Amniotic Fluid Collection Samples from Cesarean section: This research protocol will include collection of the following samples at time of cesarean section - amniotic fluid specimen, fetal membranes and placental biopsy, and a full-thickness uterine biopsy specimen. There are no associated risks with collection of amniotic fluid at time of hysterotomy/amniotomy during a cesarean section or collection of the otherwise discarded placenta and fetal membranes. Generally, the risk of taking the uterine biopsy samples is no greater that of a cesarean section alone. At this time, there is no known risk of the small amount of tissue that is to be taken by biopsy. A slight increase in the incidence and magnitude of bleeding may occur. Performing these procedures under direct observation further limits this bleeding risk. Obtaining this uterine sample will add only minimal operating time and all physicians with Obstetrics & Gynecology training should be able to perform this procedure easily. A copy of the informed consent that is in place is included for review, as is a formal biopsy protocol detailing the procedure, specimen site, specimen size, storage, etc. for completing the tissue collection at time of cesarean section.

Myometrial samples from elective hysterectomy: These patients will be undergoing an elective hysterectomy that is independent of our study. Research personnel will isolate the tissue sample following surgical removal of the uterus. A copy of the informed consent that is in place for our proposed study has been included for review, as is a formal protocol documenting instructions for completing the tissue collection at time of benign, elective hysterectomy.

Laboratory Analysis Upon acquisition of collected tissue specimens, tissue will be immediately placed in containers of cold physiologic saline solution (PSS) until transport to the laboratory at Midwestern University can be arranged. Upon arrival to the laboratory, resistance-sized myometrial and placental arteries (~250 micrometers) will be dissected in cold physiologic saline solution aerated with gas containing 21% oxygen (O2), 74% nitrogen (N2), and 5% carbon dioxide (CO2).