Uterine contraction

Background: The herbal medicine Bryophyllum pinnatum has been used as a tocolytic agent in anthroposophic medicine and, recently, in conventional settings alone or as an add-on medication with tocolytic agents such as atosiban or nifedipine. We wanted to compare the inhibitory effect of atosiban and nifedipine on human myometrial contractility in vitro in the absence and in the presence of B. pinnatum press juice (BPJ). Methods: Myometrium biopsies were collected during elective Caesarean sections. Myometrial strips were placed under tension into an organ bath and allowed to contract spontaneously. Test substances alone and at concentrations known to moderately affect contractility in this setup, or in combination, were added to the organ bath, and contractility was recorded throughout the experiments. Changes in the strength (measured as area under the curve (AUC) and amplitude) and frequency of contractions after the addition of all test substances were determined. Cell viability assays were performed with the human myometrium hTERT-C3 and PHM1-41 cell lines. Results: BPJ (2.5 μg/mL), atosiban (0.27 μg/mL), and nifedipine (3 ng/mL), moderately reduced the strength of spontaneous myometrium contractions. When BPJ was added together with atosiban or nifedipine, inhibition of contraction strength was significantly higher than with the tocolytics alone (p = 0.03 and p < 0.001, respectively). In the case of AUC, BPJ plus atosiban promoted a decrease to 48.8 ± 6.3% of initial, whereas BPJ and atosiban alone lowered it to 70.9 ± 4.7% and to 80.9 ± 4.1% of initial, respectively. Also in the case of AUC, BPJ plus nifedipine promoted a decrease to 39.9 ± 4.6% of initial, at the same time that BPJ and nifedipine alone lowered it to 78.9 ± 3.8% and 71.0 ± 3.4% of initial. Amplitude data supported those AUC data. The inhibitory effects of BPJ plus atosiban and of BPJ plus nifedipine on contractions strength were concentration-dependent. None of the test substances, alone or in combination, decreased myometrial cell viability. Conclusions: BPJ enhances the inhibitory effect of atosiban and nifedipine on the strength of myometrial contractions, without affecting myometrium tissue or cell viability. The combination treatment of BPJ with atosiban or nifedipine has therapeutic potential.

Background: In the postpartum period, a mother experiences some physical and psychological changes. Some adjustment is needed by a woman to deal with her new role as a mother. The problems that often arise are fatigue after childbirth, tension due to contraction, poor blood circulation, migraine and headache, depression, breast milk dam, nipple blisters, insomnia, and baby blues. Prolonged fatigue may cause a negative effect of depression or postpartum blues. The purpose of this study was to examine the effect of massage treatment on postpartum muscle tension. Subjects and Method: This was a randomized control trial conducted in Pleret, Bantul sub-district, Yogyakarta. A sample of 60 postpartum mothers was selected for this study and randomized into two groups. The dependent variable was muscle tension. The independent variable was massage. The data were collected by questionnaire and analyzed by Mann-Whitney test. Results: Muscle tension in the control group (86.6%) was higher than the treatment group (53.3%) and it was statistically significant (p< 0.001). Massage is effective to reduce postpartum muscle tension.

  Introduction: To compare the efficacy and safety of 25g vs. 50g of intravaginal (Posterior fornix) misoprostol for induction of labor in 100 patient from Jan 2012 to Dec 2012 at Lumbini Medical College.   Methods: One hundred pregnant lady requiring induction were randomly assigned to receive either 25 g (group A=50) or 50 g (group B=50) of intra vaginal misoprostol every 4 hrs till adequate contractions were achieved or maximum dose of 150 g was used.   Results: The onset of contraction was earlier in group B in 34 cases as compared to group A, where only 25 cases had earlier contraction ( P&gt; 0.05). 38 cases (76%) in Group B and 35 cases (70%) in Group A delivered vaginally. Induction to delivery interval was shorter(&lt;12hrs) in group B in 15 cases and in 10 cases in group A. Mean dose of Misoprostol (94micrograms) for successful induction in group B was high compared to Group A (75.5 microgram). Requirement for oxytocin infusion was higher in group A, 26% vs. 15%. Abnormal ...

To estimate the relationship between cervical length and hemorrhage leading to preterm delivery in women with placenta previa. Between October 2007 and May 2009, transvaginal cervical-length measurements were obtained in all singleton pregnancies with placenta previa identified at or beyond 24 weeks of gestation. Only women who delivered liveborn or stillborn neonates at our hospital and had placenta previa confirmed at delivery were included. Cervical length of 30 mm or less was considered short. Clinicians were blinded to cervicallength measurements. Chi-square and logistic regression were used for analysis. Of 89 identified women with placenta previa at initial ultrasonography, 68 had placenta previa at delivery, and 29 (43%) of these had a short cervix. Gestational age at cervical-length measurement was 32؎4 weeks in women with a short cervix and 33؎2 weeks in those with a longer cervix (P‫.)4.؍‬ Women with previa and a short cervix were more likely to require delivery for hemorrhage, 79% compared with 28%, and to deliver preterm, 69% compared with 21% (both P<.001). Tocodynamometer evidence of regular uterine contractions was more common with a short cervix than with a longer cervix, 69% compared with 21% (P<.001). Conversely, 64% with a cervical length greater than 30 mm had no bleeding episodes and progressed to term. In pregnancies with placenta previa, a third-trimester cervical length of 30 mm or less is associated with increased risk for hemorrhage, uterine activity, and preterm birth.

Background: Evidence on the effectiveness of local wound infiltration for cesarean section are conflicting. Objective: To assess the efficiency of local anesthetic infiltration (bupivacaine with and without lidocaine) to multiple layers of abdominal wall on postoperative pain and chronic pain following cesarean section. Material and method: A prospective, randomized, double-blinded, placebo-controlled study was conducted on 120 parturient women underwent elective cesarean section under general anesthesia. They were allocated into 3 groups for receiving the following drug; group BL: mixture of 0.5% bupivacaine 20 ml and 1% lidocaine 20 ml, group B: 0.25% bupivacaine 40 ml, and group NSS: 0.9% NaCl 40 ml; infiltrated to peritoneum(10 ml), below rectus sheath (10 ml) and subcutaneous (20 ml) before wound closure. Two doses of intramuscular diclofenac and intravenous morphine patient controlled analgesia were administered postoperatively for 24 hours. Results: Postoperative pain score at rest in group B was higher than group BL and NSS (p=0.030). No significant differences in pain score on movement and 24-hours morphine consumption were found among three groups (p=0.091 and p=0.672). Time to maximum pain in group BL and B were significantly longer than group NSS (7.5±8.1 vs 6.4±7.8 vs 4.0±6.0 hours, p=0.037). Satisfaction and side effects were comparable in three groups. Postsurgical pain syndrome at 3 months were found in group BL 19.2%, group B 14.8% and group NSS 30.8% (p=0.381). Pfannenstiel incision did not decrease pain score or morphine consumption. However, it prolonged the time to maximum pain in postoperative period. Local anesthetic injection did not prevent postsurgical pain syndrome.

Objective: The aim of the present study was to test the efficacy of epidural nalbuphine 5 mg for prevention of morphine-induced pruritus. Material and Method: Parturients, ASA I-II scheduled for elective cesarean section under epidural anesthesia were randomized into 3 groups: the placebo group, N-5 group, and N-10 group received 4 ml epidural solution containing morphine 4 mg plus either saline, nalbuphine 5 mg, and nalbuphine 10 mg respectively. Pain score at rest and on movement, incidence and severity of pruritus, sedation score, and pethidine consumption were recorded for 24 hours. Results: The 182 parturients were randomized into 60 in the placebo group, 61 in the N-5 group, and 61 in the N-10 group. The severity of pruritus was significantly lower at 3, 6, 9 and 12 h postpartum in the N-5 group and the N-10 group had a lower degree of pruritus at 3 and 6 h postpartum compared to placebo. The VAS pain scores at rest and on movement were significantly higher in the N-10 group a...

Analyzing the propagation of uterine electrical activity is poised to become a powerful tool in labor detection and for the prediction of preterm labor. Several methods have been proposed to investigate the relationship between signals recorded externally from several sites on the pregnant uterus. A promising recent method is the multivariate autoregressive (MVAR) model. In this paper we proposed a windowed (time varying) version of the multivariate autoregressive model, called W-MVAR, to investigate the connectivity between signals while still respecting their non-stationary characteristics. The proposed method was tested on synthetic signals as well as applied to real signals. The comparison between the two methods on synthetic signals showed the superiority of W-MVAR to detect connectivity even if it is non-stationary. The application of W-MVAR on multichannel real uterine signals show that the proposed method is a good tool to distinguish non-labor and labor signals. These resul...

High cholesterol is known to negatively affect uterine contractility inex vivoconditions. The aim of the present study was to reveal the effect ofin vivohypercholesterolemia on spontaneous and oxytocin-induced uterine contractility in late pregnant mouse uterus. Female Swiss albino mice were fed with high cholesterol (HC) diet (0.5% sodium cholate, 1.25% cholesterol and 15% fat) for 6 weeks and then throughout the gestation period after mating. On day 19 of gestation, serum cholesterol level was increased more than 3-fold while triglycerides level was reduced in HC diet-fed animals as compared to control animals fed with a standard diet. In tension experiments, neither the mean integral tension of spontaneous contractility nor the response to CaCl2in high K+-depolarized tissues was altered, but the oxytocin-induced concentration-dependent contractile response in uterine strips was attenuated in hypercholesterolemic mice as compared to control. Similarly, hypercholesterolemia dampene...

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 wer...

U TERINE atony can result in severe postpartum hem- orrhage, gravid hysterectomy, and maternal mortality. Oxytocin is the most commonly used agent for the prevention and treatment of uterine atony during cesarean delivery 2 ; however, rapid administration and increasing doses can result in hemodynamic instability, 3-6 cardiovascular collapse, and death. Moreover, the persistent use of oxytocin results in desensitization and down-regulation of its receptor, resulting in decreased uterine contractile response over time. Despite the demonstration of adequate uterine tone after cesarean delivery with oxytocin in low doses (<3 IU), the prevailing practice is the continuous infusion of doses greater than 20 to 40 IU. The recommended dose, timing, and rate of administration of oxytocin, as well as alternative second-line uterotonic agents, from major obstetric texts and professional obstetric societies are vague or nonexistent. The administration of oxytocin and additional uterotonic agents has been associated with significant maternal, fetal, and neonatal adverse effects. 17 These side effects, particularly those associated with oxytocin, can be related to the dose and rate of administration. Recently, improvements in perioperative patient outcomes have been demonstrated with the use of algorithms and more effective communication patterns. 20 Attention fixation on particular tasks, such as closing the uterus or responding to uterine bleeding, may lead to inattention to the dose and pattern of uterotonic agent use. The adoption of algorithms with drugs administered on a timed basis (i.e., advanced cardiac life saving) has been observed to result in improved outcomes. Moreover, active communication in the form of inquiry, the process by which information is elicited in the form of question, 22 expedites the cocreation of plans and responses among health team members. In response to these observations, we originated a clinical "rule of threes" oxytocin algorithm, which incorporates oxytocin and alternative uterotonic agents, for use during • The dosage of uterotonic agents, primarily oxytocin, at cesarean delivery is highly variable and may frequently exceed that necessary to obtain adequate uterine tone What This Article Tells Us That Is New • In 60 women randomized to treatment at cesarean delivery, a single intravenous bolus of 3 IU at delivery was as effective as continuous, wide-open infusion of oxytocin, 30 IU/500 ml despite less total oxytocin delivered • Groups did not differ in side effects associated with oxytocin

The effects of two enkephalinase inhibitors, acetorphan and thiorphan, and the enkephalin analogue [d-Ala2\p=n-\Met5]-enkephalinamide (DAMEA), on spontaneous uterine contractions were studied at day 21 of pregnancy in rats following treatment in vivo or in vitro. Acetorphan (10 mg kg\m=-\1) and thiorphan (1 mg kg\m=-\1), immediately after their i.v. administration, increased the duration of spontaneous contractions 3.4-and 4.6-fold, respectively, but did not modify the maximum amplitude. Similarly, thiorphan (40 \g=m\moll \m=-\1) increased the duration of contractions when administered in vitro. Thiorphan was ineffective during the first 30 min when given into the cerebral ventricles (50 \g=m\gper rat). These results suggest that the enkephalinase inhibitors are acting via a peripheral opioid pathway; and this conclusion is supported by the observation that thiorphan potentiated the stimulatory effect of a submaximal dose of DAMEA administered in vitro. The excitatory effects of DAMEA and the enkephalinase inhibitors were blocked by naloxone. This antagonistic effect of naloxone on uterine motility in the periparturient rat uterus, induced by either acetorphan and thiorphan or DAMEA, seems to be regulated by peripheral opiate receptors. Naloxone (10 mg kg\m=-\1 s.c.) increased both the amplitude and duration of uterine motility in vivo; however, naloxone (26 \g=m\mol l \m=-\1 and 52 \g=m\moll \m=-\1) produced a paradoxical dose-dependent biphasic effect in vitro. Baume et al, 1983) and increase the half-life of [3H]enkephalin ). Central and peripheral effects of these inhibitors were assessed by comparing the stimulatory actions of i.V. acetorphan and thiorphan, or thiorphan given i.V., i.e.v.

The effects of two enkephalinase inhibitors, acetorphan and thiorphan, and the enkephalin analogue [d-Ala2\p=n-\Met5]-enkephalinamide (DAMEA), on spontaneous uterine contractions were studied at day 21 of pregnancy in rats following treatment in vivo or in vitro. Acetorphan (10 mg kg\m=-\1) and thiorphan (1 mg kg\m=-\1), immediately after their i.v. administration, increased the duration of spontaneous contractions 3.4-and 4.6-fold, respectively, but did not modify the maximum amplitude. Similarly, thiorphan (40 \g=m\moll \m=-\1) increased the duration of contractions when administered in vitro. Thiorphan was ineffective during the first 30 min when given into the cerebral ventricles (50 \g=m\gper rat). These results suggest that the enkephalinase inhibitors are acting via a peripheral opioid pathway; and this conclusion is supported by the observation that thiorphan potentiated the stimulatory effect of a submaximal dose of DAMEA administered in vitro. The excitatory effects of DAMEA and the enkephalinase inhibitors were blocked by naloxone. This antagonistic effect of naloxone on uterine motility in the periparturient rat uterus, induced by either acetorphan and thiorphan or DAMEA, seems to be regulated by peripheral opiate receptors. Naloxone (10 mg kg\m=-\1 s.c.) increased both the amplitude and duration of uterine motility in vivo; however, naloxone (26 \g=m\mol l \m=-\1 and 52 \g=m\moll \m=-\1) produced a paradoxical dose-dependent biphasic effect in vitro. Baume et al, 1983) and increase the half-life of [3H]enkephalin ). Central and peripheral effects of these inhibitors were assessed by comparing the stimulatory actions of i.V. acetorphan and thiorphan, or thiorphan given i.V., i.e.v.

This study analysed the influence of montelukast (MON; 10 -8 -10 -4 M), a cysteinyl leukotriene receptor 1 (CysLTR1) antagonist, on the contractility of the porcine uterine smooth muscle in the luteal phase of the oesterous cycle (n=8) and in early pregnancy (n=8). Stimulation of uterine strips in the luteal phase with MON has been shown to significantly reduce the amplitude of contractions, but not to affect the tension or frequency of contractions. A statistically significant tension increase and decrease in the frequency and amplitude of contractions was observed in pigs in early pregnancy. This suggests that MON has a different effect on the parameters under study in cyclic and pregnant pigs.

The significance of uterine contractions in facilitating the successful birth of fetuses is selfevident. Timely recognition of high-risk deliveries, coupled with the administration of appropriate medication, has emerged as a promising approach to address this concern. However, the quest for effective early diagnostic methods continues to present a challenge in the field. The objective of this study was to develop a fully automated methodology for the identification of both normal and premature deliveries using EHG signals. In this study, a freely accessible database was utilized, comprising 338 signals obtained from two distinct groups of pregnant women: those who delivered at term (281 records) and those who experienced preterm delivery (57 records). The methodology employed in this study is structured into three sequential steps. Firstly, contraction segments are extracted utilizing an amplitude modulation technique. Subsequently, a process is implemented to identify consistent contractions by correlating the extracted segments with the tocodynamometer (TOCO) signal. In this step, the consistency index is assessed. Lastly, features such as energy, contraction intensity, contraction duration, peak-to-peak amplitude, log detector, and Shannon entropy are extracted from each contractile activity segment, statistical analysis was conducted using a nonparametric Mann-Whitney U test to identify significant features, and a Random forest (RF) is employed for the classification and discrimination between term and preterm births. The findings of this study show that the average consistency Index (CCI) during pre-term conditions is 0.91, contrasting with a value of 0.9 during term conditions after the extraction of contraction segments. Moreover, our experimental research results display that the performance of RF can achieve an Accuracy of 89%, Sensitivity of 85.87%, and precision of 88.76%. Our results suggest that this simple and effective method can automatically recognize uterine contraction and differentiate between term and preterm EHG signals. This may pave the way for innovative applications in the prevention of preterm labor.

Objectives  To obtain fetal heart rate, detailed fetal electrocardiography (fECG) signals and uterine contractions during labour using a single device.Design  Prospective observational study.Setting  Delivery suite at a tertiary referral hospital, London, UK.Population  Fifteen patients at median gestation of 39 weeks (range 24–41) were recruited at median cervical dilatation of 4.0 cm (range 0–10) of whom 8/15 (53%) had intact amniotic membranes.Methods  Using 12 abdominally sited electrodes, we recorded the composite abdominal signal in pregnancies intrapartum. The recorded data were analysed off‐line using a blind signal separation technique.Main outcome measures  Success of signal separation and fECG time intervals.Results  Successful fECG signal acquisition was achieved in 12/15 (80%) patients and an averaged fECG waveform acquired. In these patients, P and QRS waves were seen in all cases, and T waves in 11/12 (92%). True beat‐to‐beat heart rate (HR) was displayed and measures...

This study investigates phase synchronization in the time-frequency domain between uterine signals recorded at different sites during the same contraction from women during pregnancy and women in labor. We used the complex Morlet wavelet transform to estimate the phase synchronization between the uterine signals. The method was applied on a set of uterine bursts during pregnancy and in labor. The results indicated that the uterine bursts are more synchronized in phase during pregnancy than during labor. This phase desynchronization during labor may be a tool to differentiate between contractions during pregnancy and labor and could therefore be used in the prediction of preterm labor.

The aim of this study is to simulate the contraction phenomena in pregnant uterine. Differential equations are used to model the uterine contractions for three states, namely contracting, refractory, and resting. Since verification and validation are vital for simulation ...

Deregulation in uterine contractility can cause common pathological disorders of the female reproductive system, including preterm labor, infertility, inappropriate implantation, and irregular menstrual cycle. A better understanding of human myometrium contractility is essential to designing and testing interventions for these important clinical problems. Robust studies on the physiology of human uterine contractions require in vitro models, utilizing a human source. Importantly, uterine contractility is a three-dimensionally (3D)-coordinated phenomenon and should be studied in a 3D environment. Here, we propose and assess for the first time a 3D in vitro model for the evaluation of human uterine contractility. Magnetic 3D bioprinting is applied to pattern human myometrium cells into rings, which are then monitored for contractility over time and as a function of various clinically relevant agents. Commercially available and patient-derived myometrium cells were magnetically bioprin...

Preterm labor caused by uterine contractions is a major contributor to neonatal morbidity and mortality. Treatment intended to reduce uterine contractions include tocolytic agents, such as indomethacin. Unfortunately, clinically used tocolytics are frequently inefficient and cross the placenta causing fetal side effects. Here we show for the first time in obstetrics the use of a targeted nanoparticle directed to the pregnant uterus and loaded with a tocolytic for reducing its placental passage and sustaining its efficacy. Nanoliposomes encapsulating indomethacin and decorated with clinically used oxytocin receptor antagonist were designed and evaluated in-vitro, ex-vivo and in-vivo. The proposed approach resulted in targeting uterine cells in-vitro, inhibiting uterine contractions ex-vivo, while doubling uterine drug concentration, decreasing fetal levels, and maintaining the preterm birth rate in vivo in a pregnant mouse model. This promising approach opens new horizons for drug de...

Between at least day 9 and day 16 after ovulation the spherical equine conceptus migrates continuously throughout the uterine lumen, propelled by peristaltic myometrial contractions. This unusually long period of intrauterine movement ensures that the conceptus delivers its anti-luteolytic signal to the entire endometrium to achieve luteostasis. The present experiment tested the hypothesis that prostaglandins stimulate the myometrial contractions that result in the migration of the conceptus. Serial ultrasonographic examinations of the uteri of eight mares performed during 2 h periods between day 10 and day 18 of gestation recorded the pattern of conceptus migration before and after treatment with the cyclo-oxygenase inhibitor flunixin meglumine. Conceptus mobility was high between day 10 and day 14 after ovulation (4.3 +/- 0.8, 4.7 +/- 0.8 and 4.3 +/- 0.9 changes of location per h on day 10, day 12 and day 14, respectively), but was reduced immediately and markedly by an i.v. injec...

Prostaglandin F (PGF), PGD, PGI and thromboxane A2 (TXA2) receptors have been pharmaco- logically characterized on the non-pregnant human myometrium in vitro in accordance with the receptor classification proposed by Coleman et al. (1984). The tools for the classification include both natural prostanoids, synthetic, selective analogues and antagonists where available. 2 The potent excitatory actions of the natural FP-receptor prostanoid, PGF2., and the synthetic analogue, fluprostenol, indicate the presence of FP-receptors mediating contraction on the human myometrium. 3 PGD2 produced a biphasic response consisting of excitation followed by relaxation of spontaneous activity of the myometrium. The selective DP-receptor agonists, BW245C, produced purely inhibitory responses illustrating the presence of inhibitory DP-receptors in this tissue. The inhibitory responses of both PGD2 and BW245C were antagonized by the competitive DP-receptor antagonist, BWA 868C, providing conclusive evidence for the existence of DP-receptors. 4 PGI2 produced a biphasic response similar to PGD2. Iloprost, the EP,/IP-receptor agonist also produced a biphasic response, whilst the IP-receptor selective agonist, cicaprost, caused inhibition only, suggesting that inhibitory IP-receptors exist in the non-pregnant human myometrium. 5 The TXA2-mimetic, U46619, produced marked stimulation of the non-pregnant human myometrium and was approximately equipotent to PGF2< and fluprostenol in this effect. The actions of U46619 were competitively antagonized by the TP-receptor antagonist GR32191 showing that excitatory TP-receptors exist in this tissue. 6 All prostanoids tested, both natural and synthetic, had activity on the non-pregnant human myomet- rium in vitro, supporting the existence of a heterogeneous population of prostanoid receptors in this tissue. If the results from the present study are combined with those previously reported for EP-receptor agonists (Senior et al., 1991), it may be concluded that excitation may occur through FP-, TP-, EP3-and few EP,-receptors, whereas inhibition may occur through DP-, IP-and EP2-receptors.

Prostaglandin (PG) E analogues are used clinically to ripen the cervix and induce labour. However, selective receptor agonists may have potential to improve induction response rates or manage unwanted uterine hypercontractility in conditions such as dysmenorrhoea and preterm labour. To characterise their therapeutic value, PGE₂ analogues were used to investigate the functional EP receptor population in isolated human uterus. Responsiveness in mouse tissues was also examined to validate its use as a pre-clinical model. Uterine samples were obtained from mice at dioestrus (n=12), term gestation (n=14) and labour (n=12) and from the lower uterus of women undergoing hysterectomy (n=12) or Caesarean section (n=18). Vehicle and agonist effects were assessed using superfusion and immersion techniques. PGE₂ evoked predominant excitatory responses in mouse and relaxation in human tissues. Selective EP₄ agonists inhibited tissue activity in both non-pregnant species, whilst the EP₂ mimetic CP533536 also attenuated uterine contractions throughout gestation. The uterotonic effects of the EP_3/1 agonist sulprostone were more pronounced than the EP₁ agonist ONO-D1-004, corresponding to abundant EP₃ receptor expression in all samples. The contractile phenotype in mouse compared to human uteri may relate to regional differences as well as high expression of EP₃ receptor transcripts. Similarities in non-pregnant and gestational tissues across species suggest that EP₃ may represent a valuable translational drug target for preventing uterine hypercontractility by employing a selective antagonist. This research validates the use of non-pregnant mice for pre-clinical drug discovery of uterine EP receptor targets. To determine the utility of novel drugs and delivery systems at term pregnancy and labour, pharmacological agents interacting with EP3 receptors have clear translational value.

These studies sought to determine the intracellular ant inhibitors of intracellular calcium uptake and remechanisms underlying muscarinic receptor stimulease, c) phorbol ester activation of protein kinase C, lated phasic contractions of myometrial smooth musand d) inhibition of extracellular calcium influx [6]. Previous reports have confirmed that acetylcholine Fura-2 loaded muscle strips, along with in vitro isometstimulates contraction of various smooth muscle tisric contraction studies, we have demonstrated that sues, including myometrial smooth muscle; this effect phasic myometrial contractions stimulated in reis mediated by stimulation of the muscarinic class of sponse to (/)cis-dioxolane, a muscarinic selective aceacetylcholine receptors [8-10]. (/)Cis-dioxolane, a mustylcholine agonist, are mediated by activation of the carinic selective acetylcholine agonist, has been re-M3 receptor subtype resulting in stimulation of the ported to stimulate contractions of intestinal and bladphosphatidylinositol signaling pathway and the gender smooth muscle [9,10]; its effect on myometrial eration of cytosolic calcium oscillations.

These studies sought to determine the intracellular ant inhibitors of intracellular calcium uptake and remechanisms underlying muscarinic receptor stimulease, c) phorbol ester activation of protein kinase C, lated phasic contractions of myometrial smooth musand d) inhibition of extracellular calcium influx [6]. Previous reports have confirmed that acetylcholine Fura-2 loaded muscle strips, along with in vitro isometstimulates contraction of various smooth muscle tisric contraction studies, we have demonstrated that sues, including myometrial smooth muscle; this effect phasic myometrial contractions stimulated in reis mediated by stimulation of the muscarinic class of sponse to (/)cis-dioxolane, a muscarinic selective aceacetylcholine receptors [8-10]. (/)Cis-dioxolane, a mustylcholine agonist, are mediated by activation of the carinic selective acetylcholine agonist, has been re-M3 receptor subtype resulting in stimulation of the ported to stimulate contractions of intestinal and bladphosphatidylinositol signaling pathway and the gender smooth muscle [9,10]; its effect on myometrial eration of cytosolic calcium oscillations.

Continuous and intermittent administration of inhalational anesthetics has been successfully employed for treating pain during labor. We conjectured that intermittent sevoflurane administration would be effective for pain relief during labor without side effects to the mother or fetus. Fifty parturients breathed a mixture of 2-3% sevoflurane, oxygen and air before each uterine contraction began. The patients assessed the quality of analgesia by using a visual analogue scale (0-10) before the administration of sevoflurane and after each uterine contraction. All parturients but one were satisfied, demonstrating a mean visual analogue score before and after sevoflurane administration of 8:7 AE 1:1 and 3:3 AE 1:5, respectively. Apgar scores at 1 and 5 min were 9 (range 5-9) and 10 (range 8-10), respectively. Our findings suggest that sevoflurane could be effective for the treatment of labor pain.

Objective 1. To investigate the effects of the selective beta-3 adrenoreceptor agonist, BRL 37344, on human pregnant myometrial contractility in vitro. 2. to compare these effects with those of the beta-2 adrenoreceptor agonist, ritodrine. Methods Isometric tension recording was performed under physiological conditions in isolated myometrial strips from biopsies obtained at elective caesarean section. Following pre-incubation with oxytocin (10 -9 M), the effects of cumulative additions of BRL 37344 or ritodrine (10 -8 ±10 -3.5 M) on myometrial contractility were investigated. Results were expressed as -log EC 50 (pD 2 ) and mean maximal inhibition achieved for both drug compounds. Results BRL 37344 exerted a concentration dependant relaxant effect on myometrial contractions in all strips exposed [pD 2 , 7.26 (0.48) (SEM); mean maximal inhibition 61.98 (4.89%); n 6]. Similarly, ritodrine exerted a concentration dependant inhibition of myometrial contractility in all strips exposed [pD 2 7.40 (0.28); mean maximal inhibition 59.49 (3.97%); n 6]. There was no signi®cant difference between calculated pD 2 values (P 0.65) or mean maximal inhibition achieved (P 0.79). Conclusions The beta-3 adrenoreceptor agonist BRL 37344 induced relaxation of human myometrial contractions with similar potency to that of the most commonly used tocolytic agent ritodrine. This raises the possibility that the novel beta-3 adrenoreceptor agonists may have potential as therapeutic agents for human preterm labour. In view of their reported reduced cardiovascular side effects their potential clinical use requires further evaluation.

We read with interest the Murray, Huelsmann, and Mahlmeister (2009) commentary regarding the National Institutes of Health (NIH) workshops on fetal monitoring interpretation. We o¡er an alternative analysis of the National Institute of Child Health and Human Development (NICHD) workshops' Reports of 1997 and 2008, clari¢cation on the origin of some de¢nitions, explanation for a workgroup's inclusion or exclusion of certain patterns, and a relevant summary of current evidence and outcome data that support the NICHD terminology. From 1975 to 1995, there were more than eight di¡erent recommendations published for fetal monitoring terminology from various national and international organizations and committees. Uniformity in the terms used to describe fetal heart rate (FHR) patterns was lacking, thereby generating disagreement among and between practitioners with regard to the implications of FHR patterns and appropriate interventions directed at intrauterine fetal resuscitation. It was clear that a new paradigm for interpretation was required to advance the practice of FHR surveillance and to provide meaningful research data. To initiate essential progress toward this goal, the NICHD (1997) convened a group of experts in the ¢eld of fetal monitoring and achieved consensus on terms that characterize FHR patterns. The NICHD workgroup de¢ned FHR patterns based upon the mathematic principles of interpreting data points over timeçsimilar to the processes established for physiological monitoring in other specialties (i.e., EKG monitoring, arterial waveform analysis, etc.). As a result, decelerations in particular were characterized by timing of the onset of the deceleration to the nadir (abrupt vs. gradual). More than 90% of abrupt decelerations (less than 30 seconds from the FHR baseline to the nadir of the deceleration) are caused by cord compression and were thus categorized as variable decelerations.

We read with interest the Murray, Huelsmann, and Mahlmeister (2009) commentary regarding the National Institutes of Health (NIH) workshops on fetal monitoring interpretation. We o¡er an alternative analysis of the National Institute of Child Health and Human Development (NICHD) workshops' Reports of 1997 and 2008, clari¢cation on the origin of some de¢nitions, explanation for a workgroup's inclusion or exclusion of certain patterns, and a relevant summary of current evidence and outcome data that support the NICHD terminology. From 1975 to 1995, there were more than eight di¡erent recommendations published for fetal monitoring terminology from various national and international organizations and committees. Uniformity in the terms used to describe fetal heart rate (FHR) patterns was lacking, thereby generating disagreement among and between practitioners with regard to the implications of FHR patterns and appropriate interventions directed at intrauterine fetal resuscitation. It was clear that a new paradigm for interpretation was required to advance the practice of FHR surveillance and to provide meaningful research data. To initiate essential progress toward this goal, the NICHD (1997) convened a group of experts in the ¢eld of fetal monitoring and achieved consensus on terms that characterize FHR patterns. The NICHD workgroup de¢ned FHR patterns based upon the mathematic principles of interpreting data points over timeçsimilar to the processes established for physiological monitoring in other specialties (i.e., EKG monitoring, arterial waveform analysis, etc.). As a result, decelerations in particular were characterized by timing of the onset of the deceleration to the nadir (abrupt vs. gradual). More than 90% of abrupt decelerations (less than 30 seconds from the FHR baseline to the nadir of the deceleration) are caused by cord compression and were thus categorized as variable decelerations.

The aims of this study were to evaluate the cardiac effects of subcutaneous terbutaline on the mother and fetus. Terbutaline was given in 250 or 500 mg doses to term gravidas not in labor. The mean arterial pressure (MAP), pulse, and uterine activity were measured. The fetal heart rate (FHR), accelerations, and decelerations were recorded. There were significant increases in maternal heart rate, FHR, and FHR accelerations, and a decrease in uterine basal activity after 500 mg, but not significantly after 250 mg of terbutaline. MAP was not significantly increased with either dose, although a small mean increase was observed. Terbutaline has a direct effect on the fetal heart apart from the effect of uterine relaxation.

Objective To assess the cervical response to myometrial activity in early labour. Design Prospective observational study. Subjects Women requiring oxytocin stimulation in induced and spontaneous labours. Setting A teaching hospital in Birmingham. Simultaneous comparison of the cervical response to myometrial contractions was made on a cycle by cycle basis to deduce the properties of the cervix in early labour. Sixty-seven patients have been monitored, of whom 63 had satisfactory cervimetry data. Thirty (47.6%) women exhibited cervical contractions in response to myometrial activity. This response was only observed at dilatations up to 4 cm. The change in behaviour coincides with the transition from latent to active phases of dilatation. The length of the latent phase of labour was significantly longer in those women who exhibited cervical contractions (PcO-OOl), although the active phase was similar in the two groups (P>O.l). The group without cervical contractions exhibited a greater degree of effacement (P<0.05) and tended to have more dilated cervices (P<O.Ol) than those who showed cervical contractions. Conclusions It is possible for the cervix to contract in early labour. This response may be the result of incomplete preparation of the cervix for the process of dilatation, and is seen during what is recognised as the latent phase in those women in whom the cervix is uneffaced and undilated. These properties of the cervix may explain the poor results obtained from oxytocin stimulation of labour in the latent phase.

Introduction Bisphenols, as endocrine disruptors, may cause a wide range of health problems in humans, but so far, not all of them have been confirmed in animals, including pigs. Since animals are also exposed to bisphenols, we hypothesised that these substances may have an effect on uterine contractility in pigs. Therefore, the aim of the study was to investigate the effect of the most-used bisphenol, bisphenol A (BPA), and a selected analogue, bisphenol F (BPF), on the contractile activity of the pig uterus. Material and Methods The investigation utilised smooth muscles from immature pigs (n = 6), cyclic pigs on days 12–14 of the oestrous cycle (n = 6) or early pregnant pigs on days 12–16 of pregnancy (n = 6). Strips of the myometrium were exposed to BPA and BPF at concentrations of 10−13–10−1 M. Smooth muscle contractility was determined with equipment for measuring isometric contractions. Results BPA caused a significant decrease in contraction amplitude, and frequency and in my...

Uterine contractions during labor are discretely regulated by rhythmic action potentials (AP) of varying duration and form that serve to determine calcium-dependent force production. We have employed a computational biology approach to develop a fuller understanding of the complexity of excitation-contraction (E-C) coupling of uterine smooth muscle cells (USMC). Our overall aim is to establish a mathematical platform of sufficient biophysical detail to quantitatively describe known uterine E-C coupling parameters and thereby inform future empirical investigations of physiological and pathophysiological mechanisms governing normal and dysfunctional labors. From published and unpublished data we construct mathematical models for fourteen ionic currents of USMCs: Ca 2z currents (L-and T-type), Na z current, an hyperpolarization-activated current, three voltage-gated K z currents, two Ca 2z -activated K z current, Ca 2z -activated Cl current, non-specific cation current, Na z -Ca 2z exchanger, Na z -K z pump and background current. The magnitudes and kinetics of each current system in a spindle shaped single cell with a specified surface area:volume ratio is described by differential equations, in terms of maximal conductances, electrochemical gradient, voltage-dependent activation/ inactivation gating variables and temporal changes in intracellular Ca 2z computed from known Ca 2z fluxes. These quantifications are validated by the reconstruction of the individual experimental ionic currents obtained under voltageclamp. Phasic contraction is modeled in relation to the time constant of changing ½Ca 2z i . This integrated model is validated by its reconstruction of the different USMC AP configurations (spikes, plateau and bursts of spikes), the change from bursting to plateau type AP produced by estradiol and of simultaneous experimental recordings of spontaneous AP, ½Ca 2z i and phasic force. In summary, our advanced mathematical model provides a powerful tool to investigate the physiological ionic mechanisms underlying the genesis of uterine electrical E-C coupling of labor and parturition. This will furnish the evolution of descriptive and predictive quantitative models of myometrial electrogenesis at the whole cell and tissue levels.

Uterine contractions during labor are discretely regulated by rhythmic action potentials (AP) of varying duration and form that serve to determine calcium-dependent force production. We have employed a computational biology approach to develop a fuller understanding of the complexity of excitation-contraction (E-C) coupling of uterine smooth muscle cells (USMC). Our overall aim is to establish a mathematical platform of sufficient biophysical detail to quantitatively describe known uterine E-C coupling parameters and thereby inform future empirical investigations of physiological and pathophysiological mechanisms governing normal and dysfunctional labors. From published and unpublished data we construct mathematical models for fourteen ionic currents of USMCs: Ca 2z currents (L-and T-type), Na z current, an hyperpolarization-activated current, three voltage-gated K z currents, two Ca 2z -activated K z current, Ca 2z -activated Cl current, non-specific cation current, Na z -Ca 2z exchanger, Na z -K z pump and background current. The magnitudes and kinetics of each current system in a spindle shaped single cell with a specified surface area:volume ratio is described by differential equations, in terms of maximal conductances, electrochemical gradient, voltage-dependent activation/ inactivation gating variables and temporal changes in intracellular Ca 2z computed from known Ca 2z fluxes. These quantifications are validated by the reconstruction of the individual experimental ionic currents obtained under voltageclamp. Phasic contraction is modeled in relation to the time constant of changing ½Ca 2z i . This integrated model is validated by its reconstruction of the different USMC AP configurations (spikes, plateau and bursts of spikes), the change from bursting to plateau type AP produced by estradiol and of simultaneous experimental recordings of spontaneous AP, ½Ca 2z i and phasic force. In summary, our advanced mathematical model provides a powerful tool to investigate the physiological ionic mechanisms underlying the genesis of uterine electrical E-C coupling of labor and parturition. This will furnish the evolution of descriptive and predictive quantitative models of myometrial electrogenesis at the whole cell and tissue levels.

Analyzing the propagation of uterine electrical activity is poised to become a powerful tool in labor detection and for the prediction of preterm labor. Several methods have been proposed to investigate the relationship between signals recorded externally from several sites on the pregnant uterus. A promising recent method is the multivariate autoregressive (MVAR) model. In this paper we proposed a windowed (time varying) version of the multivariate autoregressive model, called W-MVAR, to investigate the connectivity between signals while still respecting their non-stationary characteristics. The proposed method was tested on synthetic signals as well as applied to real signals. The comparison between the two methods on synthetic signals showed the superiority of W-MVAR to detect connectivity even if it is non-stationary. The application of W-MVAR on multichannel real uterine signals show that the proposed method is a good tool to distinguish non-labor and labor signals. These resul...

The usage of the systemic opioid remifentanil in relieving the labor pain has attracted much attention recently. An optimal dosing regimen for administration of remifentanil during labor relies on anticipating the timing of uterine contractions. These predictions should be made early enough to maximize analgesia efficacy during contractions and minimize the impact of the medication between contractions. We have designed a knowledge-assisted sequential pattern analysis framework to 1) predict the intrauterine pressure in real-time; 2) anticipate the next contraction; and, 3) develop a sequential association rule mining approach to identify the patterns of the contractions from historical patient tracings. The basis of this framework is a sequential association rule based collaborative filtering strategy that dynamically selects a better training dataset from historical patient tracings, which are similar to the current patient's contraction pattern, and the current patient's most recent training time series. A k-nearest neighbors (k-NN) based least squares support vector machine (LS-SVM) approach is used to establish the long-term time series prediction. Further, a postprediction process is proposed to enhance the predictive value. The findings validate that the framework is effective, robust, and efficient for uterine contraction prediction.

We present findings suggesting that photoperiod is important in determining the sensitivity of the late-pregnant rabbit uterus to oxytocin (OT). Longitudinal myometrial strips were taken from term-pregnant and estrous rabbits and mounted in an organ bath for isometric myographic recording at different times during a 16:8-h light-dark cycle (lights on 0600–2200; n = 5/group), and the strength of contractions was registered in response to the application of OT or KCl. Strength of contractions was dose dependent and was up to 200 times greater at doses three to four orders of magnitude lower in tissue taken from pregnant animals during the light phase (0700 and 1300) than during the dark phase (2400 and 0400). Strips from nonpregnant estrous females also showed greater sensitivity and contractile force when taken in the light (0700) than in the dark (0400), although the differences were not significant. Consistent with the influence of photoperiod on uterine sensitivity to OT, strips t...

In respect to the main goal of our ongoing work for predicting preterm birth, we analyze in this paper the complexity of the uterine electromyography (EMG) by using the sample entropy (SampEn) algorithm. By considering recent methodological developments, we measure the SampEn over multiple scales using the wavelet packet decomposition method. The results obtained from the analyzed data indicate that SampEn decreases along pregnancy. Furthermore, we demonstrate that the computed SampEn parameter may discriminate between the two classes (pregnancy/labor). The results are supported by statistical analysis using t-test indicating good statistical significance with a confidence level of 95%. A surrogate data test is also performed to investigate the nature of the underlying dynamics of our experimental data. The results are very promising for monitoring pregnancy and detecting labor to help identify preterm labor.

To investigate the relationship between the oxytocin (OT) receptor (OTR) quantity and the contractile features systematically, we measured the mRNA expression levels of OTR and L-type Ca2+ channel α1C-subunit ( α 1C) and examined the regulatory mechanisms of OT-induced phasic or tonic contractions of the longitudinal smooth muscles in mouse uteri. The mRNA expression of OTR in 19.0 G (19.0 days of gestation) was greater than those in nonpregnant phases, and that of α 1C in estrus and 19.0 G was higher than in diestrus. OT-induced contractions sparsely occurred in diestrus. The OT-induced all-or-none-type phasic contractions at low concentrations were abolished by verapamil in both estrus and 19.0 G. OT-induced tonic contractions had similar pD2 values in both estrus and 19.0 G. However, the magnitude in 19.0 G was much greater than that in estrus. The large tonic contractions also occurred in PGF2α receptor (FP) knockout mice in 19.0 G despite a small amount of OTR. Verapamil and Y-...

The purpose of this study was to examine the diagnostic performance of ultrasonographic measurement of the cervical length and vaginal fetal fibronectin determination in the prediction of preterm delivery in patients with preterm uterine contractions and intact membranes. Study design: Ultrasound examination of the cervical length and fetal fibronectin determination in vaginal secretions were performed in 215 patients admitted with preterm uterine contractions (22-35 weeks) and cervical dilatation of %3 cm. Outcome variables were the occurrence of preterm delivery within 48 hours, 7 days, and 14 days of admission, delivery %32 and %35 weeks, as well as the admission-to-delivery interval. Statistical analysis included chi-square test, receiveroperator characteristic (ROC) curve analysis, logistic regression, and survival analysis. Results: The overall prevalence of preterm delivery %35 weeks was 20% (43/215). The prevalence of spontaneous preterm delivery within 48 hours, 7 days, and 14 days of admission, and delivery %32 and %35 weeks were 7.9% (17/215), 13.0% (28/215), 15.8% (34/215), 8.9% (9/101), and 15.8% (34/215), respectively. ROC curve analysis and contingency tables showed a significant relationship between the occurrence of preterm delivery and both cervical length and fetal fibronectin results (P ! .01 for each). Both tests performed comparably in the prediction of spontaneous preterm delivery. However, when fetal fibronectin results were added to those of cervical length (!30 mm), a significant improvement in the prediction of preterm delivery was achieved.

are mediated by specific angiotensin receptors. BRAIN RES BULL 35(4) [293][294][295][296][297][298] 1994.--In this study we describe a new angiotensin antagonist [Asp'-Arg*-Vap-Tyfl-Ile'-His'-D-Ala", (A-779)] selective for the heptapeptide angiotensin-(I-7) [Ang-( l-7)]. A-779 biocked the antidiuretic effect of Ang-( I-7) in water-loaded rats and the changes in blood pressure produced by Ang- ) microinjection into the dorsal-medial and ventrolateral medulla. In contrast, A-779 did not change the dipsogenic, pressor, or myotropic effects of angiotensin II (Ang II). Also, A-779 did not affect the antidiuretic effect of vasopressin or the contractile effects of angiotensin III, bradykinin, or substance P on the rat ileum. In the rostra1 ventrolateral medulla, the pressor effect produced by Ang-( 1-7) microinjection was completely blocked by A-779 but not by AT, or AT? receptor antagonists (DUP 753 and CGP 42 I 12A, respectively). Conversely, the pressor effect produced by Ang II was not changed by A-779 but was completely blocked by DUP 753. Binding studies substantiated these observations: A-779 did not compete significantly for '% Ang II binding to adren~o~ica1 membranes at up to a 1 PM concen~ation. Low affinity binding was afso observed in adrenomedullary membranes with an IC,, greater than IO PM. Our results show that A-779 is a potent and selective antagonist for Ang-(l-7). More importantly, our data indicate that specific angiotensin receptors mediate the central and peripheral actions of Ang-( I-7).

The aim of this study was to evaluate the viability of the transplanted murine uterus after cold ischaemic preservation. METHODS: Uteri of mice (6±8 weeks old) were isolated and kept at 4°C in vitro for 24 or 48 h in 0.154 mol/l NaCl or University of Wisconsin (UW) solution. Viability was evaluated by assessment of morphology and contractility in vitro. Furthermore, uteri were transplanted by vascular anastomoses to syngeneic recipients after 24 or 48 h cold ischaemic preservation in UW solution and morphology, blood ¯ow and capacity to implant transferred blastocysts were assessed 2 weeks later. RESULTS: Uteri that had been preserved for 24 h exhibited normal morphology but after 48 h preservation minimal degenerative changes were seen. Spontaneous contractions occurred in uteri after 24 h as well as 48 h cold ischaemic preservation and prostaglandin F 2a -stimulated responses were preserved. Blood ¯ow and morphology were normal 2 weeks after transplantation in uteri preserved for 24 h, while grafts preserved for 48 h had a decreased blood ¯ow and morphology showed total necrosis of the transplants. Transplanted uteri that had been preserved for 24 h developed pregnancies (in ®ve out of six animals) after embryo transfer, with offspring showing normal weight and growth trajectory. CONCLUSIONS: This study shows for the ®rst time that the mouse uterus tolerates cold ischaemic preservation and that pregnancies can be carried in transplanted uteri that have been preserved for 24 h.

The present work investigated the effect of Morinda lucida (M. lucida) extract on isolated uterine smooth muscle of pregnant and non-pregnant mice. Pregnant and non-pregnant mice were pretreated with oral stilboesterol (0.1mg/kg body weight) and killed by cervical dislocation. Thin strips of the uterus were cut and mounted in a 20-ml organ bath containing De Jalon solution bubbled with 95%O 2 -5% CO 2 gas mixture. The strips were connected to a force transducer coupled to a Grass 7D Polygraph for the recording of isometric tension. Effects of graded concentrations of oxytocin (OXY; 10 -5 -10 -2 mol/L), acetylcholine (ACh; 10 -9 -10 -5 mol/L) and M. lucida extract (0.015-1.5mg/ml) were recorded. Fresh uterine strips were then incubated with M. lucida extract for 5mins and cumulative response to OXY was repeated. Another set of fresh strips was incubated in L-NAME for 15mins and the cumulative responses to M.lucida extract were repeated. OXY resulted in increased contractile responses in both pregnant and non-pregnant uterine muscles. M. lucida resulted in relaxation of the uterine smooth muscle in both pregnant and non-pregnant mice at all doses. However, at 1.500mg/ml, M. lucida completely blocked spontaneous uterine contractions. Following incubation with L-NAME, M. lucida extract led to a slightly greater relaxation of the uterine strips. In conclusion, M. lucida reduced contractility of uterine smooth muscle in both pregnant and non-pregnant mice as well as blocking contractile responses to OXY and Ach in uterine smooth muscle of pregnant and nonpregnant mice. There was no significant alteration of M. lucida activity by L-NAME suggesting that the action of the compound on uterine muscle is not associated with impaired nitric oxide synthase.

We tested the hypothesis that sensory and nonsensory factors associated with birth stimulate respiratory behavior in the fetal and newborn rat. Late gestation (Day 21) rat fetuses were externalized from the uterus with intact umbilical connections to the dam and exposed to stimuli normally associated with labor and delivery. Onset and maintenance of respiratory movements were monitored. In the first experiment, rat fetuses were exposed to either: (i) simulated uterine contractions; (ii) cooling (26°C); (iii) umbilical cord occlusion; or (iv) air heated to intrauterine temperature (37.5°C). Subjects were videotaped for 1 h, and respiratory movements counted during tape review. Fetuses in each group showed some respiratory behavior although compression significantly elevated respiratory rate compared to other experimental conditions. All subjects in each group were respiring after 1 h, except for pups that received umbilical cord occlusion. The 100% attrition rate of the cord occlusion-alone group was reversed by combining cord occlusion with compression, or with compression and cooling, but not by combining cord occlusion with cooling. Simulated birth pups (i.e., those exposed to compression, cooling and umbilical cord occlusion) and normal, vaginally delivered pups breathed at identical rates and showed a similar pattern of postpartum breathing. These results suggest that mechanical stimulation of the fetus associated with uterine contractions plays a critical role in the maintenance of continuous respiration at birth. Possible mechanisms for the facilitative effects of compression on perinatal breathing are discussed.