Uterine Tone Research Articles

Enhanced Vascular Smooth Muscle Calcium Sensitivity and Loss of Endothelial Vasodilator Influence Contribute to Myogenic Tone Development in Rat Radial Uterine Arteries during Gestation

Uterine artery myogenic tone (MT) develops during pregnancy in hemochorial placentates such as rats and humans. The physiological reason for its appearance is not clear, and we reasoned that it may be a late pregnancy (LP) event in preparation for controlling hemorrhage during parturition. We also hypothesized that gestational increases in RhoA-induced vascular smooth muscle (VSM) calcium sensitivity are contributory and occur under the tonic influence of nitric oxide (NO). Second-order pre-placental radial arteries from early-pregnant (day 12, n = 5), mid-pregnant (day 16, n = 5) and LP (day 20, n = 20) rats were used in combination with arteriography, VSM calcium measurements, pharmacological RHO/Rho-associated protein kinase (ROCK) and nitric oxide synthase (NOS) inhibition, and Western blotting. A subgroup of LP animals (LP + LN; n = 5) treated with L-NAME from gestational days 10 to 20 were used to determine the effects of NOS inhibition on MT and RhoA expression. MT was evident throughout pregnancy, but its expression in pressurized vessels was masked by endothelial NO-induced vasodilation during early gestation. RhoA protein expression was upregulated in LP and attenuated by in vivo NOS inhibition (as was MT). In vitro RHO/ROCK inhibition decreased MT in a concentration-dependent manner without reducing VSM calcium. In summary, pressure-dependent uterine artery tone increases with gestational age due to a combination of RhoA-mediated increases in VSM calcium sensitivity and a loss of endothelial NO influence.

A randomised double-blind trial of minimal bolus doses of oxytocin for elective caesarean section under spinal anaesthesia: Optimal or not?

Background:Oxytocin administration regimens are arbitrary and highly subjective. Hence, it is essential to reinvestigate the appropriate dose for effective uterine contraction with minimal bleeding and adverse effects.Aim:To determine the optimal dose of bolus oxytocin for uterine contractions for elective caesarean section under spinal anaesthesia.Methods:Ninety term mothers (37 to 41 weeks) undergoing caesarean section electively under spinal anaesthesia were considered for the trial and divided into three groups to receive oxytocin bolus of one, two or three units. The uterine tone was assessed at 2 min after oxytocin administration. Intraoperative blood loss, mean arterial pressure, heart rate and possible side effects were also compared. Paired t-test, Kruskal-Wallis test, Chi-square test and analysis of variance (ANOVA) test with Scheffe multiple comparisons were used as inferential statistics.Results:Adequate uterine contraction was seen in 66% of participants who received one unit of oxytocin, and in 83.3% of participants who received two units of oxytocin. All those who received three units of oxytocin had an adequate uterine contraction. Blood loss was inversely related to the bolus dose of oxytocin.Conclusions:Lower bolus oxytocin doses of one and two units were inadequate for uterine contraction at elective caeserean section, while three units appeared to be effective in terms of adequate uterine contraction, reduced blood loss and stable haemodynamic system and absent side effects.

The ED50 and ED95 of oxytocin infusion rate for maintaining uterine tone during elective caesarean delivery: a dose-finding study

BackgroundThe 90% effective dose (ED90) of oxytocin infusion has been previously estimated to be 16.2 IU h− 1. However, bolus administration of oxytocin prior to the infusion may decrease the infusion dose required. The aim of this study was to estimate the ED95 for oxytocin infusion after a bolus at elective caesarean delivery (CD) in nonlaboring parturients.MethodsWe performed a randomized, triple blinded study in 150 healthy termparturients scheduled for elective CD under epidural anaesthesia. After delivery of the infant and i.v. administration of 1 IU oxytocin as a bolus, Participants were randomized to receive oxytocin infusion at a rate of 0, 1, 2, 3, 5, or 8 IU h− 1, to be given for a total of 1 h. Uterine tone assessed by the blinded obstetrician as either adequate or inadequate. Secondary outcomes included estimated blood loss (EBL), requirement for supplemental uterotonic agents, and development of side effects.ResultsThe 95% effective dose (ED95) of oxytocin infusion was estimated to be 7.72 IU h− 1 (95% confidence interval 5.80–12.67 IU h− 1). With increasing oxytocin infusion rate, the proportion of parturients who needed rescue oxytocin bolus or secondary uterotonic agents decreased. No significant among-group differences in the EBL and oxytocin-related side effects were observed.ConclusionsIn parturients who receive a 1 IU bolus of oxytocin during elective cesarean delivery, an infusion rate of oxytocin at 7.72 IU h− 1 will produce adequate uterine tone in 95% of parturients. These results suggest that the total dose of oxytocin administered in the postpartum period can be decreased when administered as an infusion after oxytocin bolus.

Carbetocin at elective caesarean section: a sequential allocation trial to determine the minimum effective dose in obese women.

Postpartum haemorrhage is a leading cause of maternal death during childbirth. There is an increasing incidence of atonic postpartum haemorrhage in developed countries, and maternal obesity has been proposed as a contributing factor. The dose-response relationship of carbetocin in obese women has not yet been determined. We conducted a double-blind, dose-finding study of carbetocin using a biased coin up-and-down design in women with a body mass index ≥40kg.m-2 undergoing elective caesarean section. The determinant for a successful response was satisfactory uterine tone, with no intra-operative need for additional uterotonic drugs. Secondary outcomes included the use of additional uterotonic drugs postoperatively, estimated blood loss and adverse effects of carbetocin administration. Thirty women were recruited to the study. The median (IQR [range]) body mass index was 44.93 (41.5-55.2 [40-66.5]) kg.m-2 . The ED90 of carbetocin was estimated as 62.9 (95%CI 57.0-68.7) μg using the truncated Dixon and Mood method, and 68 (95%CI 52-77) μg using the isotonic regression method. The estimated blood loss was 880 (621-1178 [75-2442]) ml. The overall rates of hypotension and hypertension after delivery were 40% and 6.7%, respectively, while nausea occurred in 26.7% of women. The ED90 for carbetocin in obese women at elective caesarean section is lower than the dose of 100μg currently recommended by the Society of Obstetricians and Gynaecologists of Canada, but is approximately four times higher than the previously demonstrated ED90 of 14.8μg in women with body mass index <40kg.m-2 .

Uterotonics in Elective Caesarean Delivery: A Randomised Noninferiority Study Comparing Carbetocin 20 and 100 µg

(Anaesthesia. 2019;74:190–196) Postpartum hemorrhage (PPH) is the most common cause of maternal mortality worldwide and accounts for 35% of maternal deaths. Active management of the third stage of labor is recommended in all parturients, with prophylactic uterotonic drug administration after delivery of the infant being the primary component of this active management. This strategy alone has been shown to decrease the incidence of PPH by up to 40%. The 2009 guidelines from the Society of Obstetricians and Gynaecologists of Canada (SOGC) recommended a single 100 µg intravenous bolus dose of carbetocin as the uterotonic agent of choice, rather than an oxytocin infusion, to prevent PPH after elective cesarean delivery. The rationale for recommending this dose was based on the manufacturer’s recommendation and some clinical trials. Some more recent studies, however, have suggested that doses as low as 15 µg may be effective at preventing PPH after elective cesarean delivery. The current investigators believed a larger trial comparing this smaller dose with the standard 100 µg dose was warranted to confirm these findings. This study was undertaken to compare the uterine tone intensity achieved with 20 carbetocin versus 100 µg carbetocin in women at low risk of PPH undergoing elective cesarean delivery under spinal anesthesia.

The mule (Equus mulus) as a recipient of horse (Equus caballus) embryos: Comparative aspects of early pregnancy with mares

The aim of this study was to compare the embryonic and early fetal development of horse embryos between recipient mules and mares from day 10–60 of pregnancy, in addition to hormonal (eCG and progesterone), ovarian, and uterine characteristics for approximately 4 months. Embryo donor mares (n = 5) and two groups of recipients (acyclic mules, n = 7; cyclic mares, n = 7) were used. Donor mares were monitored daily by transrectal ultrasonography and inseminated using fresh semen. Cyclic recipient mares were synchronized with the donor’s ovulation using PGF2α and deslorelin acetate. Mules were prepared for the embryo transfers with estrogen and progestagen. Embryo collection and transfer were performed 8 days after ovulation of the donor mares. Pregnancy diagnosis with ultrasonography began 1 day after embryo transfer. After pregnancy confirmation, the recipient mules received long-acting progesterone once weekly for at least 120 days. The first day of detection (day 10) of an embryonic vesicle (EV) was similar between mules and mares. A period of extensive intrauterine mobility of the embryonic vesicle was observed similarly in mules and mares from days 10–17. The day of fixation of the EV in mules tended to be 1-day earlier than in mares; however, the diameter and growth rate of the EV did not differ between the two species. The embryo proper was first detected at day 20, and the crown-rump, width, and diameter were similar between the two recipient types. The heartbeat and allantoic sac tended to be detected 1 day later in mules than in mares, while the umbilical cord was first observed around day 40 in both species. Besides the expected differences found in ovarian aspects and eCG production, similar endometrial diameter, uterine tone and echotexture, and progesterone levels were seen between the two types of recipients. In conclusion, striking ultrasound similarities in equine embryo and fetal development, and uterine characteristics were seen between mules and mares used as recipients of horse embryos.

Development and validation of a clinical score to predict the probability of successful procedure in women undergoing external cephalic version

Introduction External Cephalic Version (ECV) reduces breech presentation at term and thus contribute to the reduction of cesarean section. This study was done to determine the factors associated with the successful ECV in women with breech presentation after 36 weeks’ gestation and also to develop and validate a clinical score which could be utilized for individual patient counseling in future. Methods This was a retrospective cohort study conducted in a tertiary care center and teaching hospital in south India. Prospectively collected data from the register maintained for all ECVs performed on pregnant women with breech presentation at or more than 36 weeks’ gestation. Clinical and ultrasound parameters at the time of performing the procedure were used in the analysis. Multiple logistic regression with a stepwise backward selection procedure was used selecting potential variable to construct the model and internal validation was done with bootstrapping. Primary outcome was successful ECV defined as cephalic presentation at the end of the procedure Results Among 611 women who underwent ECV, it was successful in 70.4%. In the multiple logistic regression model, multiparity (OR4.48), AFI ≥ 7 (OR = 3.06), type of breech, posterior placental location (OR = 1.57), sacro-anterior position of breech (OR = 2.83), normal uterine tone (OR = 1.82) and fetal pole not engaged (OR = 2.82) were found to be predictive of successful ECV with good discrimination (AUC = 0.782) and acceptable calibration. Combining these factors from the model a predictive score (score 0–13) is proposed for clinical utility. Conclusions Combining clinical and ultrasound parameters into a predictive score, which is simple and effective, could be utilized in the clinical practice, once validated externally.

Carbetocin Versus Misoprostol in Prevention of Postpartum Hemorrhage in High Risk Patients

Background: Postpartum hemorrhage (PPH) is a significant problem and a major cause of maternal mortality and morbidity, resulting in up to 28% of maternal deaths. It is a potentially life-threatening complication of both vaginal and cesarean delivery, the prevalence of PPH is approximately 6% of all deliveries. Objective: The aim of this study is to compare the effectiveness and safety of carbetocin and misoprostol for the prevention of atonic postpartum hemorrhage in high risk patients. Patients and Methods: this study is a prospective clinical study which was conducted at the Department of Obstetrics and Gynecology, Aswan University Hospital, in the period from September 2017 till September 2018. One hundred cases were involved in the study and divided into 2 equal groups. The study was approved by the medical ethics committee of Aswan University Hospital and a written informed consent is obtained from all patients. Results: Significant difference was found between the two studied groups as regard mean volume of blood loss. Carbetocin group showed the lowest volume of blood loss. As regard uterine tone after treatment, carbetocin group showed the highest tone compared to misoprostol groups. Significant difference was found between the two groups as regard need for additional uterotonics. The results demonstrated an increased use of additional oxytocics in the misoprostol group (32% of cases) VS (12% of cases) in carbetocin group. Conclusion: According to the results of this study, it's concluded that carbetocin is more effective in controlling the amount of blood loss during delivery and eventually help in the prevention of postpartum hemorrhage in high risk patients.

Carbetocin Versus Misoprostol in Prevention of Postpartum Hemorrhage in High Risk Patients

Background: Postpartum hemorrhage (PPH) is a significant problem and a major cause of maternal mortality and morbidity, resulting in up to 28% of maternal deaths. It is a potentially life-threatening complication of both vaginal and cesarean delivery, the prevalence of PPH is approximately 6% of all deliveries. Objective: The aim of this study is to compare the effectiveness and safety of carbetocin and misoprostol for the prevention of atonic postpartum hemorrhage in high risk patients. Patients and Methods: this study is a prospective clinical study which was conducted at the Department of Obstetrics and Gynecology, Aswan University Hospital, in the period from September 2017 till September 2018. One hundred cases were involved in the study and divided into 2 equal groups. The study was approved by the medical ethics committee of Aswan University Hospital and a written informed consent is obtained from all patients. Results: Significant difference was found between the two studied groups as regard mean volume of blood loss. Carbetocin group showed the lowest volume of blood loss. As regard uterine tone after treatment, carbetocin group showed the highest tone compared to misoprostol groups. Significant difference was found between the two groups as regard need for additional uterotonics. The results demonstrated an increased use of additional oxytocics in the misoprostol group (32% of cases) VS (12% of cases) in carbetocin group. Conclusion: According to the results of this study, it's concluded that carbetocin is more effective in controlling the amount of blood loss during delivery and eventually help in the prevention of postpartum hemorrhage in high risk patients.

Maternal hyperuricemia as a marker of post-spinal hypotension and uterine tone during cesarean delivery: a prospective observational study.

Raised serum uric acid, a marker of oxidative stress, is known to increase vascular tone and depress myometrial contractility. A rise in serum uric acid levels has also been reported during labor, warranting its correlation with post-spinal hypotension and uterine tone. Serum UA sample was drawn from enrolled healthy, laboring parturients. Of these, 100 women who required emergency cesarean delivery were re-sampled prior to surgery. Following spinal anesthesia we recorded episodes of hypotension (MAP < 80% of baseline), use of vasopressors and supplemental uterotonics. The primary outcome was maternal hyperuricemia (1SD > appropriate for gestation age) and its correlation with post-spinal hypotension. Secondary outcomes were total vasopressors used, duration of labor and its effect on uric acid levels, uterine tone and neonatal outcome. Hyperuricemia was observed in 33% of parturients. On comparing with women showing normal uric acid levels, hyperuricemic parturients experienced significantly lower incidence of post-spinal hypotension (45.5% vs. 67.2%; p value = 0.04) and lower vasopressor usage (p value = 0.06). Clinically, an increased use of supplemental uterotonics in these parturients was noted (p = 0.20). The duration of labor had no impact on uric acid levels. Neonatal outcome was unaffected. In healthy, normotensive parturients undergoing emergency cesarean delivery, maternal hyperuricemia is associated with lower incidence of post-spinal hypotension and reduced need of vasopressors. Elevated serum uric acid levels may also be associated with decreased uterine tone, necessitating greater requirement of supplemental uterotonics. However, further prospective trials are needed to strongly establish this association.

The Effect of Intermittent Oxytocin Pretreatment on Oxytocin-induced Contractility of Human Myometrium In Vitro

(Anesth Analg. 2019;128(4):671–678. Doi:10.1213/ANE.0000000000002834) Uterine atony is the leading cause of postpartum hemorrhage, which is responsible for nearly a quarter of maternal deaths worldwide. One risk factor for uterine atony is exposure to large quantities of oxytocin during labor induction and augmentation. Compared with nonlaboring women delivering via cesarean, laboring women who receive oxytocin augmentation require 9 times more oxytocin in order to achieve adequate uterine tone during cesarean delivery (CD). Previous studies have compared a pulsatile oxytocin administration technique with continuous infusion in terms of time from initiation of infusion to delivery, but none have compared these techniques in terms of postpartum hemorrhage rate. This study aimed to compare intermittent oxytocin pretreatment with continuous oxytocin for effect on subsequent oxytocin-induced myometrial contractility.

International consensus statement on the use of uterotonic agents during caesarean section.

It is routine to give a uterotonic drug following delivery of the neonate during caesarean section. However, there is much heterogeneity in the relevant research, which has largely been performed in low-risk elective cases or women with uncomplicated labour. This is reflected in considerable variation in clinical practice. There are significant differences between dose requirements during elective and intrapartum caesarean section. Standard recommended doses are higher than required, with the potential for acute cardiovascular adverse effects. We recommend a small initial bolus dose of oxytocin, followed by a titrated infusion. The recommended doses of oxytocin may have to be increased in women with risk factors for uterine atony. Carbetocin at equipotent doses to oxytocin has similar actions, while avoiding the requirement for a continuous infusion after the initial dose and reducing the need for additional uterotonics. As with oxytocin, carbetocin dose requirements are higher for intrapartum caesarean sections. A second-line agent should be considered early if oxytocin/carbetocin fails to produce good uterine tone. Women with cardiac disease may be very sensitive to the adverse effects of oxytocin and other uterotonics, and their management needs to be individualised.

Uterine perivascular adipose tissue is a novel mediator of uterine artery blood flow and reactivity in rat pregnancy.

In vivo, uterine perivascular adipose tissue (PVAT) potentiates uterine artery blood flow in pregnant rats, although not in non-pregnant rats. In isolated preparations, uterine PVAT has pro-contractile and anti-dilatory effects on uterine arteries. Pregnancy induces changes in uterine arteries that makes them responsive to uterine PVAT signalling. An increase in uterine artery blood flow (UtBF) is a common and necessary feature of a healthy pregnancy. In the present study, we tested the hypothesis that adipose tissue surrounding uterine arteries (uterine perivascular adipose tissue; PVAT) is a novel local mediator of UtBF and uterine artery tone during pregnancy. In vivo experiments in anaesthetized Sprague-Dawley rats showed that pregnant animals (gestational day 16, term=22--23days) had a three-fold higher UtBF compared to non-pregnant animals. Surgical removal of uterine PVAT reduced UtBF only in pregnant rats. In a series of ex vivo bioassays, we demonstrated that uterine PVAT had pro-contractile and anti-dilatory effects on rat uterine arteries. In the presence of PVAT-conditioned media, isolated uterine arteries from both pregnant and non-pregnant rats had reduced vasodilatory responses. In non-pregnant rats, these responses were mediated at the level of uterine vascular smooth muscle, whereas, in pregnant rats, PVAT-media reduced endothelium-dependent relaxation. Pregnancy increased adipocyte size in ovarian adipose tissue but had no effect on uterine PVAT adipocyte morphology. In addition, pregnancy down-regulated the gene expression of metabolic adipokines in uterine but not in aortic PVAT. In conclusion, this is the first study to demonstrate that uterine PVAT plays a regulatory role in UtBF, at least in part, as a result of its actions on uterine artery tone. We propose that the interaction between the uterine vascular wall and its adjacent adipose tissue may provide new insights for interventions in pregnancies with adipose tissue dysfunction and abnormal UtBF.

The Effect of Spinal Hyperbaric Bupivacaine-Fentanyl or Hyperbaric Bupivacaine on Uterine Tone and Fetal Heart Rate in Laboring Women: A Randomized Controlled Study

(Anaesthesia. 2018;73:832–838) Combined spinal-epidural (CSE) analgesia is a rapid and effective analgesic technique during labor, with minimal motor impairment and high maternal satisfaction. Despite these advantages, high incidences of fetal heart rate (FHR) abnormalities and uterine hyperactivity have been reported with its use. This study assessed the difference between spinal bupivacaine-fentanyl or bupivacaine on baseline uterine tone and FHR abnormalities; the hypothesis was that the use of fentanyl would be associated with higher uterine tone.

Postpartum hemorrhage revisited

Postpartum hemorrhage (PPH) is a leading cause of maternal morbidity and mortality in the United States, and worldwide. Recognition of PPH is challenging, but once hemorrhage is recognized, management needs to focus on achieving adequate uterine tone and maintaining maternal hemodynamic stability. There have been several advances in the management of postpartum hemorrhage, many of which can be implemented at the labor and delivery unit level. There have been many advances in the understanding of at-risk parturients, and the use of hemorrhage protocols and safety bundles have been shown to improve patient outcomes. There are many new advances in transfusion management (e.g. fibrinogen concentrate, prothrombin complex concentrate, tranexamic acid) that can compliment traditional component therapy. Consideration should be given to transferring women at high risk for complications (e.g. invasive placentation) to a higher level facility for delivery. Although postpartum hemorrhage itself may not be preventable, early identification of blood loss, and mobilization of resources may prevent adverse outcomes. Multidisciplinary planning at the system level, ensuring that hemorrhage protocols exist, as well as for management of high-risk patients is important for improving patient outcomes.

Uterine perivascular adipose tissue: A novel regulator of uterine artery hemodynamics during normal pregnancy

IntroductionDuring pregnancy, uterine artery (UtA) blood flow increases compared to non‐pregnant state, in part due to reductions in uterine artery tone. The main objective of this study was to determine the role of adipose tissue surrounding UtA (perivascular adipose tissue, PVAT) in pregnancy‐induced changes in UtA blood flow and vasodilatory capacity. We hypothesized that uterine PVAT augments UtA blood flow and potentiates UtA dilatory responses in pregnant rats. Also, we hypothesized that pregnancy induces distinct changes in uterine PVAT morphology and gene expression as compared to other adipose depots.MethodsBlood flow and vascular reactivity were measured in UtA in pregnant and non‐pregnant rats using transonic perivascular probes and wire myography techniques, respectively. Reactivity to acetylcholine (ACh: induces endothelium‐dependent relaxation, 10−9 – 3×10−5 M) and sodium nitroprusside (SNP: induces endothelium‐independent relaxation, 10−11 – 3×10−5 M) was measured in isolated UtA in the presence and absence of PVAT‐conditioned media (PVATmedia, 30‐min incubation). Adipocyte size was determined in hematoxylin and eosin‐stained sections of uterine PVAT and ovarian adipose tissue. Gene expression was determined in uterine and periaortic PVAT using qRT‐PCR.ResultsMaximum and minimum uterine artery blood flow (UBF) were increased in UtA with intact PVAT compared to PVAT‐denuded UtA from pregnant rats (UBFmax (mL/min); denuded: 1.47 ± 0.3 vs. intact: 2.23 ± 0.2, p = 0.01; UBFmin (mL/min); denuded: 0.71 ± 0.1 vs. intact: 1.16 ± 0.1, p = 0.0002). Uterine PVAT had no effect on UBF in non‐pregnant rats (p&gt;0.9). UtA from pregnant and non‐pregnant rats incubated with PVATmedia had reduced sensitivity to ACh compared to UtA controls [Pregnant, pEC50; −PVATmedia: 7.14 ± 0.1 vs. +PVATmedia: 6.38 ± 0.2, p = 0.0006; Non‐pregnant, pEC50; −PVATmedia: 7.01 ± 0.1 vs. +PVATmedia: 6.50 ± 0.1, p = 0.005). PVATmedia had no effect on UtA sensitivity to SNP in either pregnant (p=0.48) or non‐pregnant rats (p = 0.2). Adipocyte area was greater in ovarian adipose tissue from pregnant compared to nonpregnant rats (Area (μm2/unit cell); Non‐pregnant: 563.6 ± 76.6 vs. Pregnant: 857.6 ± 31.0, p = 0.02) but there were no group differences in uterine PVAT morphology (p = 0.6). Expression of uncoupling protein‐1 (UCP‐1) was downregulated (p = 0.02) in aortic PVAT but was unchanged in uterine PVAT (p = 0.4). Expression of peroxisome proliferator‐activated receptor gamma (PPAR‐γ), adiponectin receptor (AdipoR1), and leptin were downregulated in uterine PVAT (p ≤ 0.02) but not in aortic PVAT (p ≥ 0.6).ConclusionsUterine PVAT plays a regulatory role in uterine artery hemodynamics and reactivity during normal pregnancy and has a distinct and differential gene profile as compared to other perivascular depots. Ongoing studies investigate the effects of pregnancy on cross‐talk between PVAT and maternal uterine arteries.Support or Funding InformationUniversity of North Texas Health Science Center Pilot GrantThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Pregnancy Increases Ca2+ Sparks/Spontaneous Transient Outward Currents and Reduces Uterine Arterial Myogenic Tone.

Spontaneous transient outward currents (STOCs) at physiological membrane potentials of vascular smooth muscle cells fundamentally regulate vascular myogenic tone and blood flow in an organ. We hypothesize that heightened STOCs play a key role in uterine vascular adaptation to pregnancy. Uterine arteries were isolated from nonpregnant and near-term pregnant sheep. Ca2+ sparks were measured by confocal microscopy, and STOCs were determined by electrophysiological recording in smooth muscle cells. Percentage of Ca2+ spark firing myocytes increased dramatically at the resting condition in uterine arterial smooth muscle of pregnant animals, as compared with nonpregnant animals. Pregnancy upregulated the expression of RyRs (ryanodine receptors) and significantly boosted Ca2+ spark frequency. Ex vivo treatment of uterine arteries of nonpregnant sheep with estrogen and progesterone imitated pregnancy-induced RyR upregulation. STOCs occurred at much more negative membrane potentials in uterine arterial myocytes of pregnant animals. STOCs in uterine arterial myocytes were diminished by inhibiting large-conductance Ca2+-activated K+ (BKCa) channels and RyRs, thus functionally linking Ca2+ sparks and BKCa channel activity to STOCs. Pregnancy and steroid hormone treatment significantly increased STOCs frequency and amplitude in uterine arteries. Of importance, inhibition of STOCs with RyR inhibitor ryanodine eliminated pregnancy- and steroid hormone-induced attenuation of uterine arterial myogenic tone. Thus, the present study demonstrates a novel role of Ca2+ sparks and STOCs in the regulation of uterine vascular tone and provides new insights into the mechanisms underlying uterine vascular adaptation to pregnancy.

The effects of dexmedetomidine on the bispectral index during cesarean section under general anesthesia with low-isoflurane anesthesia

Background Intraoperative awareness is a disturbing experience for all women undergoing general anesthesia for cesarean section; this may lead to posttraumatic stress which can last for many years. The bispectral index (BIS) is now widely used to evaluate the sedative hypnotic effect of anesthetic drugs. The effects of dexmedetomidine used with low concentration isoflurane on the BIS are investigated. Patients and methods After ethical approval, 40 parturients undergoing cesarean section received either normal saline, as a control group ( n =20), or 0.3 μg/kg/h intravenous dexmedetomidine 20 min before induction ( n =20) with anesthesia maintained using isoflurane 0.5 minimum alveolar concentration in 100% O 2 , fentanyl 1 μg/kg is given after fetal expulsion. Change in BIS, hemodynamic, uterine tone, Apgar score, sedative score, and pain score were recorded for all patients. Results Patients who received dexmedetomidine showed lower BIS values ( P P P P P P Conclusion The administration of dexmedetomidine 0.3 μg/kg/h is effective in maintaining a lower BIS with low-isoflurane anesthesia without adverse maternal or neonatal effects.

Effect of hCG application at different moments of the estrous cycle on corpus luteum and uterine vascularization and serum progesterone concentration in mares.

Establishment of pregnancy after embryo transfer is the ultimate goal of an embryo transfer program and increasing pregnancy rates and reducing pregnancy loss are mandatory. The utilization of treatments to improve conception rates in recipient mares has been the focus of several research groups over the last years and the results are controversial. Some studies using human chorionic gonadotrophin (hCG) found promising results. Our hypothesis was that hCG administration would cause an additional stimulation on luteal function, uterine and luteal vascularization and progesterone concentration, and the mares would have increased uterine and cervix tone. Therefore, in the present study the effects of hCG administration to induce ovulation, on day 0 (day of ovulation) or day 5 postovulation were evaluated on corpus luteum characteristics, reproductive tract vascularization, and serum progesterone concentration from ovulation until day 15 postovulation. Groups were: G1: (control) - no hCG; G2: 2500 IU of hCG to induce ovulation when a follicle greater than 35mm and uterine edema were detected; G3: 2500 IU hCG on day 0; G4: 2500 IU hCG on day 5 postovulation. Twelve mares were randomly assigned to each group, during consecutive cycles, in a Latin Square experimental design, in a total of 48 cycles. Doppler ultrasound evaluations were performed daily from day 0 until day 15 postovulation, including mesometrial vascularity, endometrial vascularity and corpus luteum vascularity. Blood samples were collected for serum progesterone concentration. Data was analyzed using the Proc Glimmix SAS Procedure for nonparametric variables and Proc Mixed for parametric parameters. There was no treatment effect for all variables studied (P > 0.05). Characteristics were only affected by day (P < 0.05). It can be concluded that hCG administration at the time points suggested in the current study did not alter the characteristics evaluated.

Efficacy of Phenylephrine in Preventing Hemodynamic Responses of Oxytocin during Elective Cesarean Section: A Randomized, Double-Blind, Controlled Trial

AbstractThis study compared hemodynamic changes and occurrence of complications following oxytocin administration with a prior injection of phenylephrine 100 μg or normal saline during elective cesarean section. Sixty-six healthy term parturients with uncomplicated, singleton pregnancy undergoing elective cesarean section under spinal anesthesia were studied. They received either intravenous phenylephrine 100 μg or normal saline before oxytocin 3 IU was administered over 30 seconds. Oxytocin dose was repeated depending on the adequacy of uterine tone. There was no significant change in systolic, diastolic, and mean arterial pressures during the initial 3 minutes following oxytocin administration in the phenylephrine group but a significant fall in mean and diastolic pressures in the saline group. Heart rate did not change significantly, and no significant complications occurred in either of the groups. To conclude, phenylephrine 100 μg administered before oxytocin injection maintained hemodynamic parameters better than normal saline injection during elective cesarean section.