Uterine Vein Research Articles

Pig blastocyst–uterine interactions

The litter-bearing pig is an invaluable model for research in reproductive biology. Spherical pig blastocysts on Day 10 of pregnancy undergo rapid morphological changes to tubular and then filamentous forms by Day 12 and a filamentous conceptus of almost 1m in length by Day 16 of pregnancy. Thus, trophectoderm of each conceptus achieves intimate contact with luminal uterine epithelium (LE) for exchange of nutrients, gases, hormones, growth factors and other key molecules for survival and development. Estrogens secreted between Days 11 and 13 of pregnancy signals pregnancy recognition to ensure that nutrients and prostaglandin F2-alpha (PGF) are secreted into the uterine lumen (exocrine secretion) rather than into the uterine vein (endocrine secretion) which would lead to regression of the corpora lutea (CL) and failure to maintain pregnancy. Pigs have a true epitheliochorial placenta. The fluid filled amnion bouys the embryo so that it develops symmetrically. The allantois fills with allantoic fluid to expand contact of the chorioallantois with uterine LE, and the allanotois supports the vascular system of the placenta. The chorion/trophectoderm in direct contact with uterine LE exchanges gases and nutrients and forms unique structures call areolae that absorb nutrient-rich secretions from uterine glands and transports them directly into fetal blood. The period from Days 20 to 70 of pregnancy is for placental growth in preparation for rapid fetal growth between Days 70 and 114 (term) of gestation. Maturation of the fetal hypothalamic–pituitary–adrenal axis leads to increases in secretion of cortisol from the fetal adrenal glands. Cortisol sets in motion secretion of estrogens, oxytocin, relaxin and prolactin, as well as increases in their receptors, which are required for delivery of piglets and for initiation of lactation and expression of maternal behavior. This review provides details of gestation in the pig with respect to uterine biology, implantation, placentation, fetal development and parturition.

Spontaneous Hemoperitoneum due to Rupture of Uterine Varicose Veins during Labor Successfully Treated by Percutaneous Embolization.

Hemoperitoneum during pregnancy is a rare but potentially lethal clinical condition. Improvements in antenatal and intrapartum care, especially in surgical and anesthetic techniques, have reduced maternal mortality; perinatal mortality remains very high (31%). Treatment is based on the systemic correction of hypovolemia and immediate surgery via laparotomy or laparoscopy in cases in the first trimester of pregnancy for hemostatic purposes. Sometimes, hysterectomy is needed. A 35-year-old Asiatic primigravid woman at 37 weeks' gestation with otherwise uneventful pregnancy came to the hospital referring abrupt-onset lumbar and abdominal pain. A bleeding uterine superficial varicocele of about 7 cm was found on the left uterine horn during Caesarean section. Interventional radiologic embolization of both uterine arteries was successfully performed. Posterior evolution of the patient was favorable. Percutaneous vascular embolization of the uterine arteries is an effective alternative treatment for many obstetrical and gynecological causes of bleeding. The main advantage of this technique is the low rate of serious complications and the preservation of reproductive function. To our knowledge, this is the first case of spontaneous intrapartum hemoperitoneum treated with this technique. An early diagnosis and a rapid indication of this therapeutic option are essential. Hemodynamic stability is needed to decide this conservative management.

A case of hemoperitoneum caused by spontaneous rupture of a superficial uterine vein at 22 weeks gestation, and obtained a term infant after surgical repair

A case of hemoperitoneum caused by spontaneous rupture of a superficial uterine vein at 22 weeks gestation, and obtained a term infant after surgical repair

Placenta accreta and beyond: Aesop's fables

We have read with great interest the article by Matsubara et al. 1. The author has described measures and techniques of cesarean hysterectomy for placenta praevia accreta that he would like to be universally achievable. In our country, the rate of cesarean sections can reach almost 80% of deliveries and gynecologic surgery teams are often confronted with cases of placenta previa, accreta or percreta. In view of the lack of standardization of cesarean hysterectomy technique, and with building up of experience, we came to develop our own technique, which is safe and can be adapted to emergency cases. First of all, placement of ureteral stents is not always possible, especially during emergencies in cases with massive bleeding. What our team usually does after the longitudinal uterine fundal incision, delivering the baby and incision closure with Vicryl® “0” hepatic needle sutures (Ethicon, Johnson and Johnson Companies, Somerville, NJ, USA) 2, is to extend the laparotomy to the pubic bone and approach the retroperitoneum just lateral to the adnexal ligaments. This step is quite essential, particularly when the placenta fills the pelvis. Next is the ligation of the utero-adnexal “ligaments” as close as possible to the uterus. Double or even triple ligation sutures are placed, owing to the great engorgement of the vessels in the pregnant uterus. We do not agree with the author's “M cross” ligation technique using needles. Then, we thoroughly identify both hypogastric arteries and clamp them with “bulldogs”, surgical tools used to clamp off or close blood vessels (Platts & Nisbett, Sheffield, UK) 3, after which we dissect these arteries distally until we reach the uterine arteries.. These are in turn clipped using Hem-o-Lok® (Teleflex, Durham, NC, USA) 4, 5 and lifted up to expose the underlying uterine veins, which are then clipped as well. The logical following step is the dissection and un-roofing of both ureters (freeing the ureters from their crossing with the uterine arteries) by bringing the clipped uterine arteries towards the uterus. A recto-vaginal space dissection is then performed and vaginal incision is carried out with the help of a flat retractor placed in the posterior vaginal fornix. The bladder is then filled to help identify its separation site and the plane is cautiously dissected with the Bowie knife. If vesical invasion is previously noted on MRI or on site, excision of a bladder patch is performed. The bladder–vaginal interface is then exposed after the bladder is brought down and the anterior vaginal incision is achieved by placing the flat retractor in the anterior cul-de-sac. The operator's index and middle fingers are subsequently positioned through the posterior and the anterior vaginal incisions, lifting the uterus up and allowing placement of two clamps alongside the cervix after verifying that the ureters are at a distance. With this technique, we are able to accomplish a total hysterectomy with minimal morbidity and nearly absent ureteral risk. Ureteral lesion is still possible despite stenting 6. Thus, it is inconceivable to execute the maneuvers depicted above without identifying the ureters. Matsubara et al. failed to perform this identification and extrapolated the cesarean hysterectomy from standard hysterectomy. Furthermore, opening the anterior and posterior vagina allows lifting the uterus, lowering the ureters and raising the latero-cervical tissue to permit risk-free section. The authors' technique is not as safe and carries the risk of massive bleeding.

The transcriptional co-repressor TLE3 regulates development of trophoblast giant cells lining maternal blood spaces in the mouse placenta

TLE3 is a transcriptional co-repressor that interacts with several DNA-binding repressors, including downstream effectors of the Notch signaling pathway. We generated Tle3-deficient mice and found that they die in utero and their death is associated with abnormal development of the placenta with major defects in the maternal vasculature. In the normal placenta, maternal blood spaces are lined, not as usual in the mammalian circulation by endothelial cells, but rather by specialized embryo-derived cells of the trophoblast cell lineage named trophoblast giant cells (TGC). Tle3 mRNA is expressed in those specialized TGC and Tle3 mutants show severe defects in differentiation of TGC-lined channels and lacunar spaces that take blood out of the labyrinth zone of the placenta and into the uterine veins. The mutants also show somewhat milder defects on the arterial-side of the maternal vascular circuit in spiral arteries and canals that take blood into the labyrinth. Notch2 and Tle3 expression patterns overlap in several TGC subtypes and we found that Tle3 and Notch2 mutants have some overlapping features. However, they also show differences implying that TLE3 may mediate some but not all of the effects of Notch2 signaling during placenta development. Therefore, formation of the different types of maternal blood spaces by different TGC subtypes is regulated by distinct molecular mechanisms.

Diagnosis of uterine vein thrombosis on transvaginal ultrasound

Deep venous thrombosis (DVT) is a potentially serious medical disorder, which may result in pulmonary embolism and death. Compression ultrasound is the investigation modality of choice for the diagnosis of DVT of the lower limb. Diagnosis of proximal thrombosis involving the pelvic veins is difficult and is usually made only after the thrombus extends into the veins of the lower limb. We present six cases of incidental uterine vein thrombosis diagnosed by transvaginal ultrasound. Our aim is to describe the technique of the examination of pelvic veins and criteria that could be used to diagnose uterine vein thrombosis. We also highlight difficulties in the management of women diagnosed with asymptomatic uterine vein thrombi as there is little evidence to guide clinicians in choosing between different treatment options.

Role of the two-point pull-up technique for treating the uterine arteries during radical hysterectomy and trachelectomy

ObjectivesTo introduce a safe and reliable method for the management of peripheral vessels around the uterine artery during abdominal radical hysterectomy or abdominal radical trachelectomy. Study designFrom 2007 to 2011, 102 patients with invasive cervical cancer underwent an abdominal radical hysterectomy. In 48 operations in 2007–2009, we performed the conventional radical hysterectomy, in which we ligated and cut the uterine arteries at their origin, and we divided the anterior leaf of the vesico-uterine ligament by blindly inserting scissors into the ureteral tunnel, pushing the ureter laterally from the cervix. In 54 operations in 2009–2011, we pulled up the origin and the bifurcation of the uterine artery using vessel tape, skeletonized the uterine artery and directly divided the superficial uterine vein, superior vesical vein and ureteric branch of the uterine artery. We also performed four radical trachelectomies using the two point pull-up method. We investigated whether this method was useful for the management of peripheral vessels around the uterine artery. ResultsThe mean total blood loss in the two point pull-up method group (485±270ml) was significantly lower than that in the conventional surgery group (686±554ml) (p<0.05). The mean length of the operation in the two point pull-up method group (481±53min) was not significantly different from the conventional surgery group (497±74min) (p=0.111). The mean number of dissected lymph nodes in the two point pull-up method group (37.2±11.6) was not significantly different from that in the conventional method group (34.4±10.2) (p=0.096). The overall survival and progression-free survival were also not substantially different between the two groups. In the radical trachelectomy, the mean blood loss was 377.5±185.6ml and the mean duration of surgery was 520.0±48.5min using the two point pull-up method. We were able to preserve both uterine arteries without accidental injury or disruptive bleeding. All four patients were menstruating normally as of the last examination. ConclusionsThe two point pull-up method enabled us to reduce intraoperative blood loss without increasing other complications during abdominal radical hysterectomy or abdominal radical trachelectomy.

Uterus Transplantation Model in Sheep With Heterotopic Whole Graft and Aorta and Cava Anastomoses

Uterine transplantation in the sheep model has been described as a partial or whole orthotopic graft from a living donor with vascular anastomoses. As an alternative to surrogate pregnancy or adoption uterus transplantation might be indicated for cases of infertility of uterine origin. The main complications might be rejection and thrombosis. The objective of this work was to develop a model of whole uterus transplantation that was applicable to the human setting, using grafts obtained from brain-dead donors, and suitable for immunologic and viability follow-up with a reduced risk of thrombosis. Two donors and 1 recipient were operated. The first graft was used for an anatomic study; the second was used for transplantation. The donor operation consisted of an en bloc harvest of the uterus, adnexa, and proximal vagina with the distal aorta and cava. After harvest the donor sheep was humanely killed. In the recipient ewe, heterotopic implantation was performed in the lower abdomen. An End-to-side anastomoses of aorta and cava were performed below the recipient's renal vessels. A cutaneous vaginal stoma was performed in the right lower quadrant. The recipient ewe was humanely killed for an autopsy study. The anatomy of uterine veins of the ewe differs from the human. The uterine and ovarian veins join, forming the utero-ovarian vein, which drains at the confluence of the common iliac to the cava. En bloc harvesting allows for rapid graft preparation, with vascular cuffs easily anastomosed with a low risk of thrombosis. The vaginal stoma seems appropriate to facilitate follow-up and graft biopsy. This approach can be a suitable experimental model applicable to humans using grafts from brain-dead donors.

Indocyanine green fluorescence imaging in the pregnant cynomolgus macaque: childbearing is supported by a unilateral uterine artery and vein alone?

Uterine blood flow is required for the maintenance of uterine viability in pregnancy and delivery, but it is unknown how many vessels are necessary for maintenance of uterine viability. The objective of this study was to examine whether unilateral uterine vessels provide sufficient nutrition in pregnancy in a cynomolgus macaque and to evaluate hemodynamics of pregnant uterus by indocyanine green (ICG) fluorescence imaging. A cynomolgus macaque with uterine blood flow maintained by the right uterine artery and vein alone was made pregnant. Hemodynamics of the uterus in the third trimester was evaluated by ICG fluorescence imaging. Pregnancy was maintained with the right uterine artery and vein. An appropriate-for-date infant was delivered by Cesarean section. ICG fluorescence imaging showed that the uterine body was imaged from the right side to the center; furthermore, collateral circulation was present from the right uterine artery toward the left uterine artery, with expanded blood flow to the left uterine body. Pregnancy and delivery were achieved in a cynomolgus macaque with a unilateral right uterine artery and vein. Blood flow to the side without the artery was complemented by vascularization of collateral circulation to the uterine artery.

An earlier rise in systemic progesterone and increased progesterone in the uterine vein during early pregnancy are associated with enhanced embryonic survival in the ewe

Improved livestock production efficiency through greater embryonic survival (ES) is of economic and animal welfare benefit. Physiological characterization of animals that are extreme outliers for ES provides a valuable opportunity to identify a naturally occurring mechanism by which this trait may be enhanced. The objective was to determine the likely cause for the lifetime history of enhanced or reduced ES in a line of ewes selected for high fecundity. To address this question, progesterone concentrations in peripheral plasma as well as ovarian and uterine venous plasma samples were compared between groups of ewes with a lifetime history of either enhanced or reduced ES. The ability of the uterus to synthesize progesterone de novo at Day 5 of gestation was also tested. Ewes with enhanced ES had an earlier rise in progesterone concentration after estrus, irrespective of pregnancy status. In addition, there were increased concentrations of progesterone in the uterine vein in enhanced ES compared with reduced ES ewes on Day 5 of gestation (8.3 ± 0.8 ng/mL and 3.9 ± 1.4 ng/mL, respectively, P < 0.05). However, there were no differences in ovarian venous plasma (enhanced ES, 1725 ± 166 ng/mL; reduced ES, 1665 ± 268 ng/mL) at Day 5 of gestation. Although the endometrial tissue of some ewes (3/8) at Day 5 of gestation expressed three of the key genes necessary for regulation of de novo synthesis of progesterone, expression was not present exclusively in either of the two ES groups and therefore was unlikely to explain differences in the uterine vein progesterone concentrations between the enhanced and reduced ES groups. Collectively, the earlier rise in progesterone concentrations in peripheral plasma during the first week of gestation in the enhanced ES animals was independent of the presence of an embryo. Moreover, increased progesterone concentrations were also observed in the uterine vein at Day 5 of gestation of the enhanced ES ewes. It is proposed that the difference in uterine vein progesterone concentration was likely due to the differences in ovarian venous blood supply rather than de novo synthesis by the uterus.

Endocrine Delivery of Interferon Tau Protects the Corpus Luteum from Prostaglandin F2 Alpha-Induced Luteolysis in Ewes

Paracrine release of ovine interferon tau (oIFNT) from the conceptus alters release of endometrial prostaglandin F2 alpha (PGF) and prevents luteolysis. Endocrine release of oIFNT into the uterine vein occurs by Day 15 of pregnancy and may impart resistance of the corpus luteum (CL) to PGF. It was hypothesized that infusion of recombinant oIFNT (roIFNT) into the uterine or jugular veins on Day 10 of the estrous cycle would protect the CL against exogenous PGF-induced luteolysis. Osmotic pumps were surgically installed in 24 ewes to deliver bovine serum albumin (BSA; n = 12) or roIFNT (200 μg/day; n = 12) for 24 h into the uterine vein. Six ewes in each treatment group received a single injection of PGF (4 mg/58 kg body weight) 12 h after pump installation. In a second experiment, BSA or roIFNT was delivered at 20 or 200 μg/day into the uterine vein or 200 μg/day into the jugular vein for 72 h in 30 ewes. One half of these ewes received an injection of PGF 24 h after pump installation. Concentrations of progesterone in serum declined in BSA-treated ewes injected with PGF, but were sustained in all ewes infused with 20 μg/day of roIFNT into the uterine vein and 200 μg of roIFNT into the jugular vein followed 24 h later with injection of PGF. All concentrations of roIFNT and modes of delivery (uterine or jugular vein) increased luteal concentrations of IFN-stimulated gene (i.e., ISG15) mRNA. Infusion of 200 μg of IFNT over 24 h induced greater mRNA concentrations for cell survival genes, such as BCL2-like 1 (BCL2L1 or Bcl-xL), serine/threonine kinase (AKT), and X-linked inhibitor of apoptosis (XIAP) and decreased prostaglandin F receptor (PTGFR) mRNA concentrations, when compared to controls. It is concluded that endocrine delivery of roIFNT, regardless of route (uterine or jugular vein), effectively protects CL from the luteolytic actions of PGF by mechanisms that involve ISGs and stabilization of cell survival genes.

Endovascular stenting for nutcracker syndrome

Nutcracker syndrome (NCS) is a rare pathology manifested by pain or hematuria in males and females alike. It can be easily overlooked, and should be considered in young men or women with symptoms of extended duration. We present a case of a 54-year-old female with chronic lower abdominal pain radiating to the left thigh of 4 years in duration. Computed tomography (CT) eventually revealed engorged left renal, gonadal, and uterine veins due to compression between the superior mesenteric artery (SMA) and the abdominal aorta, consistent with NCS. After a successful endovascular stenting and a 6-month period of antiplatelet and anticoagulant therapy, the patient returned to stable health. NCS, while rare, should be suspected in patients of both sexes with persistent pain or hematuria.

PM.06 Low Molecular Heparin Within the Uteroplacental Unit

BackgroundPerturbation of the uteroplacental haemostasis has been implicated in placenta mediated pregnancy complications in thrombophilic women. LMWH may be effective in altering local thrombin production in the uteroplacental compartment.AimWe determined...

3:54 PM Abstract No. 219 - Long-term evaluation of the medusatm vascular plug for vascular embolization: pre-clinical evaluation

Purpose Platinum embolization coils produce significant CT artifacts and require multiple devices to occlude vessels. A polymer coil-plug represents an attractive alternative, offering minimal CT artifact and occlusion in a single delivery sequence. Here, we report on the short and long-term vascular occlusion capability and biocompatibility of the novel MedusaTM Vascular Plug. Materials and Methods The MedusaTM Vascular Plug (MVP) is constructed from a radiopaque polymer and is a single unit multi-coiled design. MedusaTM Vascular Plugs (EndoShape Inc., Boulder, CO) were delivered into 72 vessels in 17 acute ovine and porcine studies and in 13 arteries in 13 chronic (26 weeks) ovine studies with contralateral metal coil controls. Devices were evaluated for occlusion time in small and large arteries and veins. Extensive laboratory biocompatability testing was also conducted on the MVP. Results In the acute studies, the MedusaTM Vascular Plugs were deployed into 61 deep femoral, femoral, common femoral, and iliac arteries ranging from 4.8 to 9.4 mm diameter (mean 6.1 mm) and in 11 hypogastric, femoral, common femoral, renal, external iliac, and uterine veins from 4 to 10 mm (mean 7 mm). Vessel occlusion was confirmed in all vessels after fluoroscopic contrast injection. The MVP formed a single compact coil pack in all studies with minimal CT artifact. Arterial occlusion times ranged from 1 to 11 minutes (mean 3.8 minutes) and venous occlusion times ranged from 0.3 to 5.5 minutes (mean 2.2 minutes). In the chronic studies, vascular occlusion was compared to contra-lateral metal coil packs (Cook SST coils, Bloomington, IN) at 21 days and 1, 3, and 6 months. At the specified end points, the MedusaTM Vascular Plugs produced occlusion in 12 of 13 animals. The control coils were occluded in 5 of 13 animals. The MVP passed 15 biocompatability tests, including toxicity, mutagenicity, pyrogenicity, cytotoxicity, and hemolysis (NAMSA and Nelson Labs). Conclusion The MedusaTM Vascular Plug provides complete occlusion of a wide variety of sizes and types of blood vessels. Durable occlusion has been confirmed in long term studies. This radiopaque polymer vascular plug may offer an attractive option to platinum embolic coils.

Spontaneous Rupture of Uterine Veins In Pregnancy

Spontaneous rupture of uterine vessels during pregnancy is a rare cause of shock that has a high rate of maternal and foetal loss. Though the usual presentation is of maternal shock, it is necessary to have in mind that possibility of blood vessels rupture may be in cases of abdominal pain &amp; hypotension of unknown origin during pregnancy. In such an event an exploratory laparatomy followed by caesarean with ligation of the uterine vessel or its branch can help in preventing a maternal mortality. The advent of modern resuscitative facilities, anaesthesia techniques have lowered mortality associated with this condition from 49% to 3.6%. DOI: http://dx.doi.org/10.3329/bjog.v25i2.13745 Bangladesh J Obstet Gynaecol, 2010; Vol. 25(2) : 85-86

Spontaneous Rupture of Uterine Vein in Twin Pregnancy

Objective. Aim of our study is to present a case of a twin pregnancy following invitro fertilization cycle complicated with hemoperitoneum at third trimester. Case. A 26-year-old nulliparous pregnant woman at 32 weeks of gestation with twin pregnancy following invitro fertilization cycle complained of abdominal pain. After 48 hours of admission, laparotomy was performed with indications of aggravated abdominal pain and decreased hemoglobin levels. Utero-ovarian vein branch rupture was detected on the right posterior side of uterus and bleeding was stopped by suturing the vein. Etiopathogenesis of the present case still remains unclear. Conclusion. Spontaneous rupture of the uterine vessels during pregnancy is a rare complication and may lead to maternal and fetal morbidity and mortality. Diagnosis and treatment are based on the clinical symptoms of acute abdominal pain and laboratory tests of hypovolemic shock signs.

Dietary melatonin supplementation alters uteroplacental amino acid flux during intrauterine growth restriction in ewes

Dietary melatonin supplementation during mid- to late-gestation increased umbilical artery blood flow and caused disproportionate fetal growth. This melatonin-induced increase in umbilical artery blood flow may alter nutrient availability to the fetus, which may lead to alterations in fetal size. The objectives of the current experiment were to determine amino acid (AA) and glucose concentrations as well as AA and glucose flux across the uteroplacenta using a mid- to late-gestation model of intrauterine growth restriction supplemented with dietary melatonin as a 2 × 2 factorial design. At day 50 of gestation, 32 ewes were supplemented with 5 mg of melatonin (MEL) or no melatonin (CON) and were allocated to receive 100% (adequate; ADQ) or 60% (restricted; RES) of nutrient requirements. On day 130 of gestation, uterine and umbilical blood flows were determined via Doppler ultrasonography during a non-survival surgery. Blood samples were collected under general anesthesia from the maternal saphenous artery, gravid uterine vein, umbilical artery, and umbilical vein for AA analysis and glucose. Total α-AA concentrations in maternal artery and gravid uterine vein were decreased (P < 0.05) in RES v. ADQ fed ewes. Maternal arterial − venous difference in total α-AA was increased (P ⩽ 0.01) in RES v. ADQ fed ewes, while total uterine α-AA flux was not different (P > 0.40) across all treatment groups. Fetal venous − arterial difference in total α-AA as well as uteroplacental flux of total α-AA were decreased (P < 0.05) in CON-RES v. CON-ADQ, and similar (P > 0.20) in MEL-RES v. CON-ADQ. Maternal concentrations and uterine flux of branched-chain AA (BCAA) were not different across all treatment groups; however, fetal uptake of BCAA was decreased (P < 0.05) in CON-RES v. CON-ADQ, and similar (P > 0.20) in MEL-RES v. CON-ADQ. Uterine uptake of glucose was not different (P ⩾ 0.08) across all treatment groups, while uteroplacental uptake of glucose was increased (P ⩽ 0.05) in RES v. ADQ ewes. In conclusion, maternal nutrient restriction increased maternal arterial − venous difference in total α-AA, while total uterine α-AA flux was unaffected by maternal nutrient restriction. Melatonin supplementation did not impact maternal serum concentrations or uterine flux of glucose or AA; however, melatonin did improve fetal BCAA uptake during maternal nutrient restriction.

Large conductance Ca2+-activated and voltage-activated K+ channels contribute to the rise and maintenance of estrogen-induced uterine vasodilation and maintenance of blood pressure.

Uterine blood flow (UBF) increases greater than 4-fold 90 min after systemic estradiol-17β (E2β) in nonpregnant sheep and remains elevated longer than 6-8 h; mean arterial pressure (MAP) is unchanged. Large-conductance Ca(+2)-activated (BK(Ca)) and voltage-activated (K(V)) K(+) channels contribute to the acute rise in UBF; their role in maintaining UBF and MAP longer than 90 min is unknown. We examined this in five nonpregnant, ovariectomized ewes with uterine artery (UA) flow probes and catheters in a UA for infusion of K(+) channel inhibitors and uterine vein to sample venous effluent. Animals received systemic E2β (1.0 μg/kg; control), E2β+UA tetraethylammonium (TEA; 0.4-0.8 mm, n = 4), and E2β+UA 4-aminopyridine (4-AP; 0.01-0.08 mm, n = 4) to block BK(Ca) and K(V), respectively, while monitoring MAP, heart rate, and UBF. Uterine cGMP synthesis was measured. Ninety minutes after E2β, UBF rose 4.5-fold, uterine vascular resistance (UVR) fell greater than 5-fold and MAP was unchanged [78 ± 0.8 (sem) vs. 77 ± 1.5 mm Hg] in control studies and before UA inhibition with TEA and 4-AP. Between 90 and 120min, UBF, UVR, and MAP were unchanged after E2β alone. E2β+TEA dose dependently decreased ipsilateral UBF and increased UVR (24 ± 8.9 and 38 ± 16%, respectively, at 0.8 mm; P < 0.03); MAP was unchanged. Contralateral UBF/UVR were unaffected. E2β+4-AP also dose dependently decreased ipsilateral UBF and increased UVR (27 ± 5.3 and 76 ± 18%, respectively, at 0.08 mm; P < 0.001); however, MAP rose 27 ± 6.9% (P ≤ 0.006). E2β increased uterine cGMP synthesis greater than 3.5-fold and was unaffected by local K(+) channel inhibition. BK(Ca) and K(V) contribute to the rise and maintenance of E2β-induced uterine vasodilation, which is partially cGMP dependent. Systemic vascular K(V) also contributes to maintaining MAP after systemic E2β.

Individualized Radical Hysterectomy Procedure Using Intraoperative Electrical Stimulation for Patients With Cervical Cancer

In this study, by monitoring the varied distributions of nerve fascicles using intraoperative electrical stimulation (IES), we sought to establish an individualized operation based on the patient's unique nerve distribution pattern, and to determine whether this technique would result in a higher preservation rate. Radical hysterectomy was performed from 2002 to 2010. Patients in group A are the 48 cases from 2002 to 2007 in which nerve-sparing radical hysterectomy using IES as our previous report was performed. Patients in group B are the 38 cases from 2008 to 2010 in which we used our new method, which was individualized to each patient. Urodynamic study (UDS) was used to confirm nerve preservation. Nerve preservation was defined as confirming distinct detrusor contraction during urinary voiding. In group B, nerve preservation rate was higher than in group A (75% vs 9 0%, P = 0.067). We classified the case-by-case nerve anatomy as whether the nerve fascicle was mainly on the medial side or on the lateral side of the deep uterine vein. The lateral type anatomy was observed unilaterally in 6 cases and bilaterally in 1 case. In summary, the lateral type anatomy was observed in 8 (29%) of 28 sides. In the cases evaluated by UDS, the positive predictive value of IES was 95% in group A and 100% in group B. Our method of IES showed a high positive predictive value of nerve preservation as confirmed by UDS. By delineating the nerve tract in detail using IES, it is possible to individualize the operation based on each patient's anatomy, with an improved nerve preservation rate.

Induction of Anti-Apoptotic Genes in Cultured Small, Large, and Mixed Ovine Luteal Cells in Response to Interferon-Tau.

Ovine interferon-t (oIFNT) is released from the conceptus into the uterine vein by Day 15 of pregnancy and has endocrine action through inducing IFN-stimulated genes (ISGs) in the corpus luteum (CL). ISG15 is localized to large and small luteal cells based on immunohistochemical staining. Large luteal cells contain prostaglandin F2a (PGF) receptors that stimulate apoptotic signalling and release of oxytocin (OXT) when bound to ligand. Small luteal cells contain OXT receptors, and when activated also induce apoptotic signalling. Infusion of 200 μg of recombinant (r) oIFNT/day into the uterine vein of ewes induces cell survival genes in the CL such as B cell lymphoma extra large (Bcl-XL), protein kinase B (Akt), and X-linked inhibitor of apoptosis (XIAP). Endocrine delivery of 20 μg roIFNT/day into the uterine vein or subcutaneously to the ewes on Day 10 of the estrous cycle also protects the CL against the decline in serum progesterone concentrations caused by injection with PGF on Day 11 of the estrous cycle. Others have described the presence of PGE2 in uterine vein blood and its luteotrophic action on the CL. The present in vitro studies tested the hypothesis that IFNT, rather than PGE2, induces ISG15 and cell survival genes in cultured luteal cells. CLs were collected from adult ewes on Day 10 of the estrous cycle and prepared as mixed (1 x 106/ml) or separated by elutriation into small (2 x 106/ml ) or large (5 x 105/ml) luteal cells. Luteal cells were cultured for 24 h in M199 media supplemented with 10% FBS. The media was replaced with serum-free media and treatments were added to cells. Differences are described as P < 0.05. Culture with 0.1, 1, 10 or 100 ng/ml of roIFNT (108 U/mg) revealed that 1 ng/ml induced ISG15 mRNA concentrations (determined by semi-quantitative RTPCR) in small, large and mixed cells that were in the upper (~80-90% of maximum) linear response to these doses of roIFNT. Cells also were cultured with 10 μM OXT, 3.5 ng/ml PGF and 3.5 ng/ml PGE2, based on effective doses published by others. The roIFNT induced greater BCL-XL, Akt and XIAP mRNA concentrations in small, mixed and large cell cultures when compared to controls. PGE2, PGF and OXT had no effect on ISG15 mRNA concentrations. PGF caused a slight induction of Bcl-XL in large luteal cells and a slight reduction of XIAP mRNA concentrations in mixed luteal cells, but otherwise had no effect. OXT had no effect on Bcl-XL or Akt, but slightly upregulated XIAP mRNA concentrations in small luteal cells. PGE2 had no effect on XIAP, but slightly decreased Bcl-XL and Akt mRNA concentrations in small and large cells. It is concluded that ISG15, Bcl-XL, Akt, and XIAP mRNAs are up regulated within 24h in response to roIFNT treatment of isolated small, large and mixed luteal cells, and that this induction is independent of the actions of PGE2, OXT and PGF. These results are similar to the results obtained in previous in vivo studies using osmotic infusion of roIFNT into the uterine vein of ewes. Endocrine action of IFNT might entail up regulation of ISGs as well as cell survival genes to assist with providing resistance of the CL to PGF, but also in longer-term resilience in context of continued production of progesterone. USDA-NIFA-AFRI 2011–67015–20067. Dr. Sereno is on sabbatical leave from Embrapa Cerrados, Planaltina, DF, Brazil.