Pharmacological Interventions in Labor and Delivery.

While there is not a wide range of pregnancy-specific drugs, there are some very specific high-risk areas of obstetric care for which unique pharmacological approaches have been established. In preterm birth, labor induction and augmentation, and the management of postpartum hemorrhage, these pharmacological approaches have become the bedrock in managing some of the most common and problematic areas of antenatal and intrapartum care. In this review, we summarize the existing established and emerging evidence that supports and broadens these pharmacological approaches to obstetric management and its impact on clinical practice. It is clear that existing therapeutics are limited. They have largely been developed from our knowledge of the physiology of the myometrium and act on hormonal receptors and their signaling pathways or on ion channels influencing excitability. Newer drugs in development are mostly refinements of these two approaches, but novel agents from plants and improved formulations are also discussed.

Lippia origanoides essential oil induces tocolytic effect in virgin rat uterus and inhibits writhing in a dysmenorrhea mouse model.

ETHNOPHARMACOLOGICAL RELEVANCE: The species Lippia origanoides Kunth, popularly known as "salva-de-marajó", is used in Brazilian traditional "quilombola" communities to treat menstrual cramps and uterine inflammation. AIM OF THE STUDY: Evaluate the spasmolytic activity of Lippia origanoides essential oil (LOO) on experimental models of uterine conditions related to menstrual cramps and investigate its mechanism of action. MATERIALS AND METHODS: Virgin rat-isolated uterus was mounted in the organ bath apparatus to evaluate the spasmolytic effect of LOO on basal tonus and contractions induced by carbachol, KCl, or oxytocin. We used pharmacological agents to verify the relaxation mechanism of LOO. The evaluation of uterine contractility in virgin rats, after treatment with LOO for three consecutive days, was carried out by the construction of a concentration-response curve with oxytocin or carbachol. The primary dysmenorrhea animal model was replicated with an injection of estradiol cypionate in female mice for three consecutive days, followed by intraperitoneal application of oxytocin. RESULTS: LOO relaxed the rat uterus precontracted with 10-2 IU/mL oxytocin (logEC50 = 1.98 ± 0.07), 1 µM carbachol (logEC50 = 1.42 ± 0.07) or 60 mM KCl (logEC50 = 1.53 ± 0.05). It was also able relax uterus on spontaneous contractions (logEC50 = 0.41 ± 0.05). Preincubation with glibenclamide, propranolol, phentolamine or L-NAME in contractions induced by carbachol did not alter significantly the relaxing effect of LOO. However, in the presence of 4-aminopyridine, CsCl or tetraethylammonium there was a reduction of LOO potency, whereas the blockers methylene blue, ODQ, aminophylline and heparin potentiated the LOO relaxing effect. Preincubation with LOO in a Ca2+ free medium at concentrations of 27 µg/mL or 81 µg/mL reduced the contraction induced by carbachol. The administration of LOO for 3 days did not alter uterus contractility. The treatment with LOO at 30 or 100 mg/kg intraperitoneally, or 100 mg/kg orally, inhibited writhing in female mice. The association of LOO at 10 mg/kg with nifedipine or mefenamic acid potentiated writhing inhibition in mice. CONCLUSIONS: The essential oil of L. origanoides has tocolytic activity in rat isolated uterus pre-contracted with KCl, oxytocin, or carbachol. This effect is possibly related to the opening of potassium channels (Kir, KV, and KCa), cAMP increase, and diminution of intracellular Ca2+. This relaxant effect, probably, contributed to reduce the number of writhings in an animal model of dysmenorrhea being potentiated by nifedipine or mefenamic acid. Taken together, the results here presented indicate that this species has a pharmacological potential for the treatment of primary dysmenorrhea, supporting its use in folk medicine.

Effects of Solvents, Emulsions, Cosolvents, and Complexions on Ex Vivo Mouse Myometrial Contractility.

A great need exists to develop tocolytic and uterotonic drugs that combat poor, labor-related maternal and fetal outcomes. A widely utilized method to assess novel compounds for their tocolytic and uterotonic efficacy is the isometric organ bath contractility assay. Unfortunately, water-insoluble compounds can be difficult to test using the physiological, buffer-based, organ bath assay. Common methods for overcoming solubility issues include solvent variation, cosolvency, surfactant or complexion use, and emulsification. However, these options for drug delivery or formulation can impact tissue function. Therefore, the goal of this study was to evaluate the ability of common solvents, surfactants, cosolvents, and emulsions to adequately solubilize compounds in the organ bath assay without affecting mouse myometrial contractility. We found that acetone, acetonitrile, and ethanol had the least effect, while dimethylacetamide, ethyl acetate, and isopropanol displayed the greatest inhibition of myometrial contractility based on area under the contractile curve analyses. The minimum concentration of surfactants, cosolvents, and human serum albumin required to solubilize nifedipine, a current tocolytic drug, resulted in extensive bubbling in the organ bath assay, precluding their use. Finally, we report that an oil-in-water base emulsion containing no drug has no statistical effect beyond the control (water), while the drug emulsion yielded the same potency and efficacy as the freely solubilized drug.

Augmented KCa2.3 Channel Feedback Regulation of Oxytocin Stimulated Uterine Strips from Nonpregnant Mice.

Uterine contractions prior to 37 weeks gestation can result in preterm labor with significant risk to the infant. Current tocolytic therapies aimed at suppressing premature uterine contractions are largely ineffective and cause serious side effects. Calcium (Ca2+) dependent contractions of uterine smooth muscle are physiologically limited by the opening of membrane potassium (K+) channels. Exploiting such inherent negative feedback mechanisms may offer new strategies to delay labor and reduce risk. Positive modulation of small conductance Ca2+-activated K+ (KCa2.3) channels with cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine (CyPPA), effectively decreases uterine contractions. This study investigates whether the receptor agonist oxytocin might solicit KCa2.3 channel feedback that facilitates CyPPA suppression of uterine contractions. Using isometric force myography, we found that spontaneous phasic contractions of myometrial tissue from nonpregnant mice were suppressed by CyPPA and, in the presence of CyPPA, oxytocin failed to augment contractions. In tissues exposed to oxytocin, depletion of internal Ca2+ stores with cyclopiazonic acid (CPA) impaired CyPPA relaxation, whereas blockade of nonselective cation channels (NSCC) using gadolinium (Gd3+) had no significant effect. Immunofluorescence revealed close proximity of KCa2.3 channels and ER inositol trisphosphate receptors (IP3Rs) within myometrial smooth muscle cells. The findings suggest internal Ca2+ stores play a role in KCa2.3-dependent feedback control of uterine contraction and offer new insights for tocolytic therapies.

Supplementation with Spirulina platensis Prevents Uterine Diseases Related to Muscle Reactivity and Oxidative Stress in Rats Undergoing Strength Training.

Strength training increases systemic oxygen consumption, causing the excessive generation of reactive oxygen species, which in turn, provokes oxidative stress reactions and cellular processes that induce uterine contraction. The aim of this study was to evaluate the possible protective effect of Spirulina platensis (SP), an antioxidant blue algae, on the contractile and relaxation reactivity of rat uterus and the balance of oxidative stress/antioxidant defenses. Female Wistar rats were divided into sedentary (CG), trained (TG), and T + supplemented (TG50, TG100) groups. Reactivity was analyzed by AQCAD, oxidative stress was evaluated by the malondialdehyde (MDA) formation, and the antioxidant capacity was measured by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. Strength training increased contractile reactivity and decreased the pharmaco-mechanical component of relaxing reactivity in rat uterus. In addition, training decreased oxidation inhibition in the plasma and exercise increased oxidative stress in the uterine tissue; however, supplementation with algae prevented this effect and potentiated the increase in antioxidant capacity. Therefore, this study demonstrated that food supplementation prevents changes in reactivity and oxidative stress induced by strength training in a rat uterus, showing for the first time, that the uterus is a target for this exercise modality and antioxidant supplementation with S. platensis is an alternative means of preventing uterine dysfunction.

Labor induction with randomized comparison of cervical, oral and intravaginal misoprostol.

BACKGROUND: This study attempts to evaluate the safety and effectiveness of 50µgm intracervical misoprostol in comparison with intravaginal and sublingual for the induction of labor at term pregnant women. METHODS: This study is designed as a parallel clinical trial study. Three hundred and fifteen term pregnancies requiring induction of labor were treated with the maximum used misoprostol intracervical, sublingual, and vaginal doses. Participants were randomly allocated into three groups of 105. The dose was repeated every 4 h until adequate uterine contraction and Bishop Score were achieved. The duration of induction to births, time to the active phase, the rate of births, and the need for caesarean section were compared in three groups. Additionally, labor course and side effects were recorded and analyzed. Data were analyzed using SPSS software. A significance level of p <  0.05 was considered for statistical analyses. FINDINGS: Labor was successfully induced in all cases most (63%) of which required a single dose of misoprostol. Ninety-three (93.0%, p <  0.05) cervical participants proceeded to vaginal births. This figure was also the same in the vaginal and sublingual group of 83 cases (83.0%). The other 41 cases received caesarean section with more indications of failure to progress and meconium-stained liquor. The results indicated that 278 (92.7%) births were achieved in less than 10 h. Time from start of medication to the active phase of labor and childbirth was 3.01 ± 0.86 and 6.1 ± 1.3 h in the Cervical group, 4.2 ± 0.66 and 8.4 ± 0.92 h in the sublingual group, and 5.06 ± 1.1 and 9.2 ± 1.5 h in the vaginal group respectively (p < 0.001). The Caesarean rate was lower in the cervical group than in the two other groups (p = 0.05). No significant differences were observed between the study groups in terms of Apgar score and meconium-stained amniotic fluid. Furthermore, no maternal and neonatal complications were observed. CONCLUSION: In addition to the sublingual and intravaginal routes of administration, intracervical misoprostol at a single dose of 50µgm appears to be an effective method for induction of labor in women with an unfavorable cervix. Like all medical interventions, a discussion of the risks, benefits, and alternatives to induction of labor with this medication in each woman should be undertaken before treatment. TRIAL REGISTRATION: This clinical study was approved by the Iranian Registry of Clinical Trials with IRCT ID: IRCT20190415043278N1 . Registration date was on May 13, 2019 and May 27, 2019 respectively ( http://www.irct.ir ).

Chloroorganic (DDT) and organophosphate (malathion) insecticides impair the motor function of the bovine cervix.

Dichlorodiphenyltrichloroethane (DDT) is a representative organochlorine insecticide and a known endocrine disruptor. Malathion is an organophosphate insecticide and a next-generation pesticide. Previously, it was shown that oxytocin (OT) and prostaglandins (PGs) are involved in the mechanism of the adverse effect of DDT on bovine myometrial contractions. However, disruption of myometrial contractions without disruption of cervical activity may not be sufficient to cause preterm delivery. Hence, the aim of this study was to determine the effects of insecticides on the function of the bovine cervix at preovulation period. Bovine cervical cells or strips were treated with DDT or malathion (0.1-100 ng/ml), and neither DDT nor malathion (each at a dose of 100 ng/ml) affected the viability of cervical cells. Malathion (0.1-10 ng/ml) and the high doses of DDT (10 ng/ml) decreased the force of cervical contractions, in contrast to a low dose of DDT (0.1 ng/ml). Both insecticides also decreased the mRNA expression of the OT receptor and the level of the second messenger (inositol triphosphate, IP3). Moreover, DDT decreased the amount of other second messengers (diacylglycerol, DAG), while malathion decreased the amount of gap junction protein (GAP). Only malathion increased PGE2 and decreased PGF2α secretion, while neither insecticide had an effect on both prostaglandins synthesis. Both DDT and malathion impaired cervical contractions, secretory function and cellular signalling. It is also possible that malathion-mediated induction of locally produced PGE2 can be followed by cervical softening. Admittedly it was shown that DDT and malathion can evoke failures in the regulation of motor function of cervix during oestrus cycle, while their harmful effect on gestation can be also not excluded.

Evaluating aminophylline and progesterone combination treatment to modulate contractility and labor-related proteins in pregnant human myometrial tissues.

Progesterone (P4) and cyclic adenosine monophosphate (cAMP) are regarded as pro-quiescent factors that suppress uterine contractions during pregnancy. We previously used human primary cells in vitro and mice in vivo to demonstrate that simultaneously enhancing myometrial P4 and cAMP levels may reduce inflammation-associated preterm labor. Here, we assessed whether aminophylline (Ami; phosphodiesterase inhibitor) and P4 can reduce myometrial contractility and contraction-associated proteins (CAPs) better together than individually; both agents are clinically used drugs. Myometrial tissues from pregnant non-laboring women were treated ex vivo with Ami acutely (while spontaneous contracting) or throughout 24-h tissue culture (±P4); isometric tension measurements, PKA assays, and Western blotting were used to assess tissue contractility, cAMP action, and inflammation. Acute (1 h) treatment with 250 and 750 µM Ami reduced contractions by 50% and 84%, respectively, which was not associated with a directly proportional increase in whole tissue PKA activity. Sustained myometrial relaxation was observed during 24-h tissue culture with 750 µM Ami, which did not require P4 nor reduce CAPs. COX-2 protein can be reduced by 300 nM P4 but this did not equate to myometrial relaxation. Ami (250 µM) and P4 (100 and 300 nM) co-treatment did not prevent oxytocin-augmented contractions nor reduce CAPs during interleukin-1ß stimulation. Overall, Ami and P4 co-treatment did not suppress myometrial contractions more than either agent alone, which may be attributed to low specificity and efficacy of Ami; cAMP and P4 action at in utero neighboring reproductive tissues during pregnancy should also be considered.

Ethanolic Extracts of Adlay Testa and Hull and Their Active Biomolecules Exert Relaxing Effect on Uterine Muscle Contraction through Blocking Extracellular Calcium Influx in Ex Vivo and In Vivo Studies.

Dysmenorrhea is one of the most prevalent disorders in gynecology. Historically, adlay (Coix lachryma-jobi L. var. Ma-yuen Stapf.) has been explored for its anti-tumor, pain relief, anti-inflammatory, and analgesic effects. The aim of this study was to evaluate the effects of adlay seeds on the inhibition of uterine contraction and thus dysmenorrhea relief, in vitro and in vivo. HPLC-MS and GC were used to elucidate the ethyl acetate fraction of adlay testa ethanolic extract (ATE-EA) and ethyl acetate fraction of adlay hull ethanolic extract (AHE-EA). Elucidation yielded flavonoids, phytosterols, and fatty acids. Uterine leiomyomas and normal adjacent myometrial tissue were evaluated by oxytocin- and PG-induced uterine contractility. ATE-EA and AHE-EA suppressed uterine contraction induced by prostaglandin F2 alpha (PGF2α), oxytocin, carbachol, and high-KCl solution ex vivo. In addition, the external calcium (Ca2+) influx induced contraction, and increased Ca2+ concentration was inhibited by ATE-EA and AHE-EA on the uterine smooth muscle of rats. Furthermore, ATE-EA and AHE-EA effectively attenuated the contraction of normal human myometrium tissues more than adjacent uterine leiomyoma in response to PGF2α. 3,5,6,7,8,3',4'-Heptamethoxyflavone and chrysoeriol produced a remarkable inhibition with values of IC50 = 24.91 and 25.59 µM, respectively. The experimental results showed that treatment with ATE-EA at 30 mg/day effectively decreased the writhing frequency both on the oxytocin-induced writhing test and acetic acid writhing test of the ICR mouse.

Identification of a novel distension-evoked motility pattern in the mouse uterus.

The dynamic changes in uterine contractility in response to distension are incompletely understood. Rhythmic, propagating contractions of nonpregnant uterine smooth muscle occur in the absence of nerve activity (i.e., myogenic), events that decline during pregnancy and reemerge at parturition. We therefore sought to determine how myogenic contractions of the nonpregnant uterus are affected by distension, which might provide mechanistic clues underlying distension-associated uterine conditions such as preterm birth. Uteri isolated from nulliparous adult female mice in proestrus were video imaged to generate spatiotemporal maps, and myoelectrical activity simultaneously recorded using extracellular suction electrodes. Motility patterns were examined under basal conditions and following ramped intraluminal distension with fluid to 5 and 10 cmH2O. Intraluminal distension caused pressure-dependent changes in the frequency, amplitude, propagation speed, and directionality of uterine contractions, which reversed upon pressure release. Altered burst durations of underlying smooth muscle myoelectric events were concurrently observed, although action potential spike intervals were unchanged. Voltage-gated sodium channel blockade [tetrodotoxin (TTX); 0.6 µM] attenuated both the amplitude of contractions and burst duration of action potentials, whereas all activity was abolished by L-type calcium channel blockade (nifedipine; 1 µM). These data suggest that myogenic motility patterns of the nonpregnant mouse uterus are sensitive to changes in intraluminal pressure and, at high pressures, may be modulated by voltage-gated sodium channel activity. Future studies may investigate whether similar distension-evoked changes occur in the pregnant uterus and the possible pathophysiological role of such activity in the development of preterm birth.

Quercetin affects uterine smooth muscle contractile activity in gilts.

Quercetin is a polyphenolic flavonoid occurring in leaves, stems, flowers and fruits of many plants. In traditional Chinese medicine, it is used as a natural therapeutic agent with a broad spectrum of activities (antioxidant, neuroprotective, anti-inflammatory, anticancer, antibacterial and antiviral). Moreover, quercetin affects function of the reproductive tract, however the knowledge of this activity is still fragmentary. Therefore, this study aimed to determine the influence of quercetin on the contractile activity of the porcine myometrium collected from immature (n = 6), cyclic (n = 6) and early pregnant (n = 6) gilts. Strips of the myometrium (comprising longitudinal and circular layer) were resected from the middle part of the uterine horns and the isometric contractions were recorded. After 60-90 min of preincubation, the strips were stimulated with quercetin in increasing (10-13-10-1 M) concentrations and the changes in the tension amplitude and frequency of contractions were measured. Quercetin decreased (P<0.01-0.001) the amplitude of contractions at concentrations 10-11-10-1 M and 10-10-10-1 M in cyclic and early pregnant groups, respectively. The frequency of contractions decreased in all groups but was the highest (at concentrations 10-11-10-1 M; P<0.05-0.001) in the cyclic group and the lowest (at concentrations 10-5-10-1 M; P<0.01) in the immature group. The tension decreased only in the cyclic group after quercetin administration in high concentrations (10-6-10-1 M; P<0.05-0.01). The results indicate that quercetin causes relaxation of the porcine uterine smooth muscle but this activity is strongly related to the physiological status of the gilts.

The mechanism of action of oxytocin antagonist nolasiban in ART in healthy female volunteers.

RESEARCH QUESTION: What are the effects of the oxytocin receptor (OTR) antagonist nolasiban on uterine contractions, endometrial perfusion and endometrial mRNA expression? DESIGN: Randomized, double-blind, parallel-group, mechanism-of-action study with nolasiban. Forty-five healthy, pre-menopausal women were treated with placebo, 900 mg or 1800 mg nolasiban on the day corresponding to blastocyst transfer. Ultrasonographic uterine contraction frequency and endometrial perfusion were assessed, and endometrial biopsies analysed by next-generation sequencing. RESULTS: Both doses of nolasiban showed decreased contraction frequency and increased endometrial perfusion depending on the time point assessed. At 1800 mg, 10 endometrial genes (DPP4, CNTNAP3, CNTN4, CXCL12, TNXB, CTSE, OLFM4, KRT5, KRT6A, IDO2) were significantly differentially expressed (adjusted P < 0.05). Of these, OLFM4, DPP4 and CXCL12 were regulated in the same direction as genes involved in implantation during the window of implantation. In addition, three genes (DPP4, CXCL12 and IDO2) were associated with decidualization and endometrial receptivity. CONCLUSIONS: These data expand our knowledge of the mechanism of action of nolasiban in increasing pregnancy rates after embryo transfer. The results suggest more marked effects of nolasiban 1800 mg compared with the 900 mg dose, supporting testing at higher doses in IVF patients.

Effect of maternal oxytocin on umbilical venous and arterial blood flows during physiological-based cord clamping in preterm lambs.

BACKGROUND: Delayed umbilical cord clamping (UCC) after birth is thought to cause placental to infant blood transfusion, but the mechanisms are unknown. It has been suggested that uterine contractions force blood out of the placenta and into the infant during delayed cord clamping. We have investigated the effect of uterine contractions, induced by maternal oxytocin administration, on umbilical artery (UA) and venous (UV) blood flows before and after ventilation onset to determine whether uterine contractions cause placental transfusion in preterm lambs. METHODS AND FINDINGS: At ~128 days of gestation, UA and UV blood flows, pulmonary arterial blood flow (PBF) and carotid arterial (CA) pressures and blood flows were measured in three groups of fetal sheep during delayed UCC; maternal oxytocin following mifepristone, mifepristone alone, and saline controls. Each successive uterine contraction significantly (p<0.05) decreased UV (26.2±6.0 to 14.1±4.5 mL.min-1.kg-1) and UA (41.2±6.3 to 20.7 ± 4.0 mL.min-1.kg-1) flows and increased CA pressure and flow (47.1±3.4 to 52.8±3.5 mmHg and 29.4±2.6 to 37.3±3.4 mL.min-1.kg-1). These flows and pressures were partially restored between contractions, but did not return to pre-oxytocin administration levels. Ventilation onset during DCC increased the effects of uterine contractions on UA and UV flows, with retrograde UA flow (away from the placenta) commonly occurring during diastole. CONCLUSIONS: We found no evidence that amplification of uterine contractions with oxytocin increase placental transfusion during DCC. Instead they decreased both UA and UV flow and caused a net loss of blood from the lamb. Uterine contractions did, however, have significant cardiovascular effects and reduced systemic and cerebral oxygenation.

Acute Pulmonary Edema Induced by a Low Dose of Ritodrine Hydrochloride: A Case Report.

OBJECTIVE: Acute pulmonary edema associated with ritodrine hydrochloride is a rare, life-threatening complication, and dose and duration of ritodrine use are closely associated with this pathology. We report a case of acute pulmonary edema associated with short-duration infusion of ritodrine hydrochloride in a patient with pectus excavatum as an underlying factor. CASE REPORT: A 30-year-old healthy pregnant woman was treated with oral ritodrine for tocolysis between 31 and 35 weeks of pregnancy. At 36 weeks of gestation, she went into preterm labor, with premature rupture of the membrane and breech presentation, and received an infusion of ritodrine hydrochloride for a few hours. Although she was normotensive until labor onset, mild hypertension and proteinuria were recognized. Intraoperatively, a funnel-chest deformity was observed, and she developed postoperative pulmonary edema associated with dyspnea and wet cough and confirmed on chest radiography and arterial gas analysis, and recovered with supportive care. CONCLUSION: Small-dose infusion of ritodrine hydrochloride might cause pulmonary edema in patients with underlying medical problems, including pectus excavatum.

Using shear wave elastography to assess uterine tonicity after vaginal delivery.

This study aims to evaluate the feasibility and clinical interest of shear wave elastography, by quantitatively estimating the baseline stiffness of the myometrium before and after placental expulsion. We conducted a prospective cohort study of women at term, without known risk factors for postpartum hemorrhage, who gave birth via spontaneous labor in our tertiary center. Myometrium tonicity was evaluated based on measurements of shear wave speed (SWS) in the anterior uterine corpus. All data points were collected by a single operator. Measurements were carried out at three different time points: after fetal delivery (T1), after placental delivery (T2) and 30 min after placental delivery (T3). Our primary objective was to assess the feasibility of this new imaging technique. Ten valid SWS measurements obtained at each of the three different time points were considered as a positive primary outcome. Our secondary objectives were to evaluate the difference in median myometrial shear wave velocity between each time point, as well as to determine the correlation between myometrial shear wave velocity and patients' characteristics. 38 women were recruited during the study period, of whom 34 met the study criteria. 1017 SWS measurements were obtained. The median time to perform measurements was 16 s for one value, and 2 min 56 s for ten. For 11 women (32%) it was not possible to achieve ten SWS at T1 as placental expulsion immediately followed the birth of the newborn. One patient experienced placental retention and only measurements at T1 were performed. For all other patients, we were successfully able to obtain all measures as intended. There was no difference in the mean shear wave speed between the three time points. After adjustments for confounders, we observed a significant correlation for total blood loss (correlation coefficient = - 0.26, p < 0.001, units of oxytocin (correlation coefficient = - 0.34, p = 0.03), and newborn weight (correlation coefficient = - 0.08, p = 0.001). It is feasible to assess uterine tonicity by shear wave imaging, after placental expulsion. We did not observe a variance in uterine tonicity between the three time points. Women who had higher blood loss, received more units of oxytocin and/or those with newborns of a higher weight exhibited lower shear wave speed measures.

A study of uterine inertia on the spontaneous of labor using uterine electromyography.

OBJECTIVE: The purpose of this study is to analyze uterine electromyography burst patterns in patients with spontaneous labor and patients with uterine inertia. MATERIALS AND METHODS: Uterine electromyography was recorded using 4 silver/silver chloride electrodes placed periumbilical. Thirty women in the spontaneous labor were enrolled. Uterine electromyography was also recorded from patients with uterine inertia before and after oxytocin treatment. EMG bursts were characterized by analysis of multiple variables including burst frequency, duration, root mean squared, amplitude, and total power. RESULTS: There were significant reductions (P < .01) in all EMG burst characteristics. In addition, uterine electromyography parameters were all increased after oxytocin treatment and were comparable (P > .05) to patients in spontaneous labor. CONCLUSIONS: Uterine electromyography can be used effectively to distinguish patients progressing with spontaneous labor from patients that develop uterine inertia. Uterine inertia is characterized by reduced EMG activity and failure of cervical dilation. Uterine electromyography is a quantitative, non-invasive assessment tool that contributes to the diagnosis, evaluation and management of patients with spontaneous labor and uterine inertia.

Relaxant Effects of the Aqueous Extract of Excoecaria grahamii (Euphorbiaceae) Leaves on Uterine Horn Contractility in Wistar Rats.

In uterine smooth muscle, the effects of Excoecaria grahamii are not yet documented. To fill this gap, we investigated the pharmacological effect of Excoecaria grahamii on the contraction of the rat isolated uterine horns. The isolated segments were exposed to different concentrations of the aqueous extract of Excoecaria grahamii leaves and pharmacological drugs. The results showed that Excoecaria grahamii aqueous extract decreased the amplitude and frequency by concentration-related manner. IC50 values were 2.4 and 2.6, respectively, for amplitude and frequency. Our study revealed that the extract did not act through histamine H2-receptors or the nitric oxide pathway. It also inhibited uterine contractions induced by oxytocin and potassium chloride (KCl). These data suggest that Excoecaria grahamii active compound can be used for calming uterine contractions. The action of Excoecaria grahamii showed that it can be useful to fight against diseases which caused uterotonic effects. It can be useful to prevent preterm birth and pains caused by menstruations but further investigation is needed to clarify the mechanism action.

Calcium signaling cascades differentially regulate PGF2α-induced myometrial contractions in water buffaloes (Bubalus bubalis).

This study unravels the differential involvement of calcium signaling pathway(s) in PGF2α-induced contractions in myometrium of nonpregnant (NP) and pregnant buffaloes. Compared to the myometrium of pregnant animals, myometrium of NP buffaloes was more sensitive to PGF2α as manifested by changes in mean integral tension (MIT) and tonicity. In the presence of nifedipine, myometrial contraction to PGF2α was significantly attenuated in both NP and pregnant uteri; however, mibefradil and NNC 55-0396 produced inhibitory effects only in uterus of pregnant animals, thus suggesting the role of extracellular Ca2+ influx through nifedipine-sensitive L-type Ca2+-channels both in NP and pregnant, but T-type Ca2+ channels seem to play a role only during pregnancy. Entry of extracellular Ca2+ is triggered by enhanced functional involvement of Pyr3-sensitive TRPC3 channels and Rho-kinase pathways as evidenced by a significant rightward shift of the concentration-response curve of PGF2α in the presence of Pyr3 and Y-27632 in NP myometrium. But significant down-expressions of TRPC3 and Rho-A proteins during pregnancy apparently facilitate uterine quiescence. In the presence of Ca2+-free solution and cyclopiazonic acid (SERCA blocker), feeble contraction to PGF2α was observed in both NP and pregnant myometrium which suggests minor role of intracellular source of Ca2+ in mediating PGF2α-induced contractions in these tissues.

Conflicting Nongenomic Effects of Progesterone in the Myometrium of Pregnant Rats.

Recently, it has been suggested that progesterone affects the contractile activity of pregnant myometrium via nongenomic pathways; therefore, we aimed to clarify whether progesterone causes and/or inhibits pregnant myometrial contractions via nongenomic pathways. Our in vitro experiments using myometrial strips obtained from rats at 20 days of gestation revealed that progesterone caused myometrial contractions in a concentration- and time-dependent manner at concentrations up to 5 × 10-7 M; however, this effect decreased at concentrations higher than 5 × 10-5 M. Similarly, progesterone enhanced oxytocin-induced contractions up to 5 × 10-7 M and inhibited contractions at concentrations higher than 5 × 10-5 M. Conversely, progesterone did not enhance high-KCl-induced contractions but inhibited contractions in a concentration- and time-dependent manner at concentrations higher than 5 × 10-7 M. We also found that RU486 did not affect progesterone-induced contractions or the progesterone-induced inhibition of high-KCl-induced contractions; however, progesterone-induced contractions were blocked by calcium-free phosphate saline solution, verapamil, and nifedipine. In addition, FPL64176, an activator of L-type voltage-dependent calcium channels, enhanced high-KCl-induced contractions and rescued the decrease in high-KCl-induced contractions caused by progesterone. Together, these results suggest that progesterone exerts conflicting nongenomic effects on the contractions of pregnant myometrium via putative L-type voltage-dependent calcium channels.

A comparative study of transdermal nitroglycerine patch and oral nifedipine in preterm labor.

Background: Currently, the main goal for the use of tocolytic therapy is to delay the birth so as to allow the use of corticosteroids for accelerating fetal lung maturity and maternal transfer to a tertiary care center and thereby reducing neonatal morbidity and mortality. Aims and Objectives: The aims amd objectives were to compare the safety and efficacy of transdermal nitroglycerine patch with oral nifedipine as a tocolytic agent to arrest preterm labor and prevent preterm birth. Materials and Methods: Based on the selection criteria, 50 patients were selected randomly in Group A and Group B. Group A women were given transdermal nitroglycerin patch, which delivered 10 mg Nitroglycerin (NTG) over 24 h and it was applied to the woman's abdomen followed by another patch of 10 mg after 1 h if contractions persisted. After 24 h, it was replaced by a fresh patch. Group B women were given an oral loading dose of nifedipine 20 mg followed by a similar dose if contractions persisted after 1 h. A maintenance dose of 10 mg thrice daily was given if contractions were suppressed. Patients were monitored from the time of admission to the time of discharge. Results: The mean duration of prolongation of pregnancy in Group B (3.68 ± 1.91 days) was significantly more than Group A (2.78 ± 1.39 days). Headache was seen significantly more in Group A (42%) than group B (6%). Tachycardia, hypotension, and palpitation showed no statistically significant difference between them. There was no statistically significant difference in the birth weight of the babies in both the groups. Conclusion: Nifedipine is a safe and effective drug in prolonging preterm labor and has minimal maternal and neonatal side effects.

RésuméContexte: Actuellement, le principal objectif de l'utilisation de la thérapie tocolytique est de retarder la naissance afin de permettre l'utilisation de corticostéroïdes pour accélérer la maturité pulmonaire fœtale et le transfert maternel vers un centre de soins tertiaires et ainsi réduire la morbidité et la mortalité néonatales. Buts et objectifs: Les buts et objectifs étaient de comparer l'innocuité et l'efficacité du timbre transdermique de nitroglycérine avec la nifédipine par voie orale comme agent tocolytique pour arrêter le travail prématuré et prévenir l'accouchement prématuré. Matériel et méthodes: Sur la base des critères de sélection, 50 patientes ont été sélectionnées au hasard dans les groupes A et B.Les femmes du groupe A ont reçu un patch transdermique de nitroglycérine, qui a administré 10 mg de NTG en 24 h et appliqué sur l'abdomen de la femme suivi d'un autre patch de 10 mg après 1 h si les contractions ont persisté. Après 24 h, il a été remplacé par un nouveau patch. Les femmes du groupe B ont reçu une dose de charge orale de 20 mg de nifédipine suivie d'une dose similaire si les contractions persistaient après 1 h. Une dose d'entretien de 10 mg trois fois par jour était administrée si les contractions étaient supprimées. Les patients ont été suivis du moment de l'admission au moment de la sortie. Résultats: La durée moyenne de prolongation de la grossesse dans le groupe B (3,68 ± 1,91 jours) était significativement plus élevée que dans le groupe A (2,78 ± 1,39 jours). Les céphalées étaient significativement plus observées dans le groupe A (42%) que dans le groupe B (6%). La tachycardie, l'hypotension et les palpitations n'ont montré aucune différence statistiquement significative entre elles. Il n'y avait pas de différence statistiquement significative du poids à la naissance des bébés dans les deux groupes. Conclusion: La nifédipine est un médicament sûr et efficace pour prolonger le travail prématuré et a des effets secondaires maternels et néonatals minimes.