Intrauterine Pressure Recordings Research Articles

Effect of clinical doses of buserelin on in vivo bovine uterine activity at estrus

For successful fertilization, a transfer system named "rapid sperm transport" generated by uterine contractions plays a crucial role. The purpose of this in vivo study was to investigate the effect of buserelin, a GnRH agonist widely used for ovulation induction after mating or artificial insemination, on bovine uterine contractility which supports rapid sperm transport at estrus. In vivo uterine contractile activity was measured by intrauterine pressure recording technique. In the study, the spontaneous uterine contractile activities of 28 cows at estrus were observed for 30 min. The cows were randomly divided into 4 treatment groups which have 7 cows each of and were injected appropriate agents as follows; two different clinical doses of buserelin (10.5 μg, 21 μg), oxytocin (50 IU) and control (placebo). Following treatment, drug-induced uterine activity was measured for 60 min. There were no differences in terms of frequency in all groups observed. Oxytocin which is known as an effective uterotonic increased the amplitude and area under curve of contraction at estrus. Two different doses of buserelin were observed to have no effect on uterine contractile activity in cows throughout 60 min. It was concluded that GnRH has no function on bovine uterine contractility which plays a role in sperm transportation at estrus.

Application of Telemetric Recording of Intrauterine Pressure in Rats as a Method to Investigate Mechanisms of Drug-Induced Dystocia

Application of Telemetric Recording of Intrauterine Pressure in Rats as a Method to Investigate Mechanisms of Drug-Induced Dystocia

Physiology of Upward Transport in the Human Female Genital Tract

The uterus and fallopian tubes represent a functionally united peristaltic pump under the endocrine control of ipsilateral ovary. We have examined this function by using hysterosalpingoscintigraphy (HSS), recording of intrauterine pressure, electrohysterography, and Doppler sonography of the fallopian tubes. An uptake of labeled particles into the uterus was observed during the follicular and luteal phases of the cycle after application into the vagina. Transport into the oviducts, however, could only be demonstrated during the follicular phase. Furthermore, the predominant transport was into the tube ipsilateral to the ovary containing the dominant follicle. The pregnancy rate following spontaneous intercourse or insemination was higher in those women in whom ipsilateral transport could be demonstrated. The amount of material transported to the ipsilateral tube was increased after oxytocin administration, as demonstrated by radionuclide imaging and by Doppler sonography following instillation of ultrasound contrast medium. An increase in the basal tone and amplitude of contractions was observed after oxytocin administration. These results support the idea that the uterus and fallopian tubes act as a peristaltic pump, which increases transport of sperm into the oviduct ipsilateral to the ovary bearing the dominant follicle. Oxytocin appears to play a critical role in this peristaltic pump. A failure of the peristaltic mechanism is possibly responsible for infertility. We propose the term tubal transport disorder (TTD) as a nosological entity. Results from HSS could be a useful adjunct for choosing treatment modalities in patients with patent fallopian tubes suffering from infertility. These patients may be better served with in vitro fertilization (IVF).

The effect of a single oxytocin or carbetocin treatment on uterine contractility in early postpartum dairy cows

The uterotonic characteristics and effectiveness of a single treatment with either oxytocin or carbetocin were quantified in early postpartum dairy cows after normal, uncomplicated calvings. Both the short-term (within 4 h), and the long-term effects (between 12 and 36 h) of the two treatments were compared. Between 14 and 16 h after parturition, 27 multiparous Holstein-Friesian dairy cows, without fetal membrane retention, were selected and divided into three groups. The first group ( n = 9) was administered 50 IU oxytocin intramuscularly, the second group ( n = 10) received 0.35 mg carbetocin, while animals of the third group ( n = 8), serving as a control, were administered 5 mL saline solution. A transcervically introduced open tip catheter system was used for the non-invasive acquisition of the intrauterine pressure (IUP) recording. After digitalization, the signals were analyzed, using a specially adapted graphical software program. A significant short-term effect was found both in the oxytocin and carbetocin treated groups from the analysis of the contraction frequencies (FREQ) and of the total area under the curve (TAUC). After significant peaking during the first post-treatment hour, the values of the parameters for these two groups remained higher during the second hour, returning to the initial levels again during the third hour and reaching the level of the control group by the 12th hour. Mean amplitude (AMP), duration (DUR) and area under the curve (AUC) of pressure cycles were not significantly affected by any of the treatments. Although mean FREQ and TAUC significantly declined from the initial values to 12, 24 and 36 h in all groups, mean AMP and AUC in the oxytocin and carbetocin treated groups, and mean DUR only in the carbetocin treated group to 12 and 36 h, the long-term analysis revealed no significant treatment differences for any IUP parameters. Because treatment with either oxytocin, or carbetocin elicited similar uterotonic effects in healthy, early postpartum cows, it cannot be expected, that using carbetocin in preference to oxytocin, will result in a more beneficial clinical effect on uterine involution during this period.

Barusiban, A New Highly Potent and Long-Acting Oxytocin Antagonist: Pharmacokinetic and Pharmacodynamic Comparison with Atosiban in a Cynomolgus Monkey Model of Preterm Labor

Preterm labor (PTL) represents a significant unmet clinical need that affects up to 20% of all pregnancies and is a leading cause of preterm delivery and associated neonatal morbidity and mortality. Therapeutic options are limited, with existing drug therapy (tocolytics) compromised by side effects and limited efficacy. Because oxytocin (OT) is likely to be involved causally in PTL, this study compared two OT receptor antagonists, barusiban and atosiban, for their tocolytic effects. OT was given to instrumented pregnant cynomolgus monkeys to induce contractions and simulate PTL. Barusiban or atosiban was then given iv (bolus or infusion) to evaluate inhibitory effects on uterine contractions, measured by telemetric recording of intrauterine pressure. Both antagonists had high efficacy (96-98% inhibition of intrauterine pressure) and rapid onset of action (0.5-1.5 h). Barusiban was three to four times more potent than atosiban, which was attributed to its higher affinity and selectivity for the OT receptor. Barusiban also had a much longer duration of action (>13-15 h, compared with 1-3 h for atosiban). The inhibitory effects of barusiban were reversible within 1.5-2.5 h by high-dose OT infusion. Overall, barusiban's improved potency, long duration of action, and reversibility may provide an improved tocolytic for treatment of PTL.

The Patterns of Uterine Contractility in Normal Menstruating Women: From Physiology to Pathology

The nonpregnant uterus shows uterine activity throughout the menstrual cycle. This uterine activity was detected both by single strep tissue and by using intrauterine pressure recordings in vitro and in vivo. Today, ultrasound has made it possible to study this activity with a noninvasive approach and to assess uterine contractions (UCs) in real-time movements of the uterus. Throughout the menstrual cycle, wavelike activity patterns of the reproductive organ were established. These patterns are under control of steroid hormones. Adequate UCs may provide for gamete/embryo transportation throughout the uterotubal cavities and successful embryo implantation in spontaneous and/or assisted reproduction. Inadequate UCs may produce ectopic pregnancy, miscarriages, retrograde bleeding with dysmenorrhea, and endometriosis.

Inhibitory effects of SR 49059 on oxytocin-and vasopressin-induced uterine contractions in non-pregnant women

Background. Compounds that block uterine oxytocin and vasopressin V1a receptors have a therapeutic potential in preterm labor and primary dysmenorrhoea. The orally active vasopressin V1a receptor antagonist, SR49059, inhibits the effect of vasopressin on human uterine activity in vivo, but the influence on the response to oxytocin is unknown. Methods. In a placebo-controlled, double-blind, parallel-group, four-dose comparison, the inhibitory effect of SR 49059 on oxytocin- and vasopressin-induced uterine contractions in humans was investigated. Sixteen healthy female subjects, who had previously undergone sterilization with tubal ligation, participated in intrauterine pressure recordings at one of the first 3 days of bleeding of two menstrual cycles. Intravenous bolus injections of 10 pmol/kg body weight of vasopressin (Period 1) and of 50 pmol/kg body weight of oxytocin (Period 2) were given 1 h before and 1 , 2 and 4 h after oral administration of 0 (placebo), 25 , 75 or 200 mg of SR 49059. The area between the recording curve and zero level of intrauterine pressure (AUC) was calculated. Vital signs as well as urine and plasma safety parameters were measured. The plasma concentrations of oxytocin, vasopressin and the study drug were also estimated. Results. The plasma concentrations of SR 49059 appeared to be dose related, with mean maximal values of 62.0, 163.7 and 468.0 ng/ml in the 25, 75 and 200 mg dose groups, respectively, in Period 1 with vasopressin and 34.4, 116.7 and 418.0 ng/mL, respectively, in Period 2 with oxytocin. Tmax was observed at about 1 h. The cumulative AUC over 50 min after vasopressin injection per se was significantly higher than that after oxytocin in spite of a five times lower dose and lower plasma concentrations. Pretreatment by SR 49059 caused a dose-related reduction in AUCs for vasopressin, whereas no such effect was seen for oxytocin. With vasopressin as an agonist, a lower diastolic blood pressure was observed in all SR 49059 treatment groups, but not with oxytocin. Conclusions. The much higher potency of vasopressin compared with oxytocin on uterine activity in non-pregnant women at menstruation was confirmed. SR 49059 dose-dependently inhibits vasopressin-induced contractions, whereas such an effect was not seen with the present doses of SR 49059 and oxytocin. A marked reduction by SR 49059 of diastolic blood pressure after vasopressin injection was observed, indicating an inhibition by this compound of vascular vasopressin receptors.

Endometrial wave-like activity in the non-pregnant uterus.

The non-pregnant uterus shows wave-like activity throughout the menstrual cycle. This uterine activity was first detected using intra-uterine pressure recordings. The use of ultrasound has made it possible to study the movements of the uterus in a non-invasive manner. Throughout the menstrual cycle, several wavelike activity patterns have been described; these patterns change throughout the menstrual cycle and are governed by steroid hormones. An adequate wave pattern seems to be related to successful reproduction in spontaneous cycles and assisted reproduction. Further insight into the phenomenon of endometrial wave-like activity might offer an opportunity to correct abnormal wave patterns and thereby improve pregnancy rates.

Physiologic role of nitric oxide in the maintenance of uterine quiescence in nonpregnant and pregnant sheep

Objective: This study evaluated the role of nitric oxide in the maintenance of uterine quiescence in nonpregnant and pregnant ewes. Study Design: Sixteen ovariectomized nonpregnant and 10 pregnant (115 days’ gestation) chronically instrumented ewes were studied. Uterine contractility was assessed by electromyography and intrauterine pressure recordings. Nitric oxyde synthase inhibition was induced with nitro-L -arginine methyl ester or aminoguanidine (4.5 mg/kg per hour) given during estrogen replacement with 17β-estradiol (100 μg/d) or in late gestation. In the pregnant group we evaluated the ability of nitric oxide synthase inhibition to alter the responsiveness to oxytocin-induced uterine contractility. Blood pressure and common internal iliac artery blood flow were assessed to confirm nitric oxide synthase inhibition. In addition, the effects of the nitric oxide donor nitroglycerin and the cyclooxygenase inhibitor indomethacin were studied in nonpregnant sheep. The effect of nitric oxide in vitro on myometrial spontaneous and induced contractions was also studied. Results: In nonpregnant estrogen-replaced sheep, nitric oxide synthase inhibition and nitroglycerin administration did not alter uterine contractility, despite significant changes in blood pressure. In contrast, indomethacin decreased electromyographic results to 70% of baseline after 1 hour and 47% after 2 hours. In pregnant ewes nitric oxide synthase inhibition failed to alter uterine contractility in response to oxytocin. These findings are in contrast to results of the in vitro study in which nitric oxide was shown to relax sheep myometrium. Conclusion: The absence of significant effects of nitric oxide synthase inhibition and nitric oxide donors on uterine contractility in vivo suggests that nitric oxide does not play a physiologic role in the regulation of uterine contractility in nonpregnant or pregnant ewes. (Am J Obstet Gynecol 2000;183:191-8.)

Physiologic role of nitric oxide in the maintenance of uterine quiescence in nonpregnant and pregnant sheep

Objective: This study evaluated the role of nitric oxide in the maintenance of uterine quiescence in nonpregnant and pregnant ewes. Study Design: Sixteen ovariectomized nonpregnant and 10 pregnant (115 days’ gestation) chronically instrumented ewes were studied. Uterine contractility was assessed by electromyography and intrauterine pressure recordings. Nitric oxyde synthase inhibition was induced with nitro-L -arginine methyl ester or aminoguanidine (4.5 mg/kg per hour) given during estrogen replacement with 17β-estradiol (100 μg/d) or in late gestation. In the pregnant group we evaluated the ability of nitric oxide synthase inhibition to alter the responsiveness to oxytocin-induced uterine contractility. Blood pressure and common internal iliac artery blood flow were assessed to confirm nitric oxide synthase inhibition. In addition, the effects of the nitric oxide donor nitroglycerin and the cyclooxygenase inhibitor indomethacin were studied in nonpregnant sheep. The effect of nitric oxide in vitro on myometrial spontaneous and induced contractions was also studied. Results: In nonpregnant estrogen-replaced sheep, nitric oxide synthase inhibition and nitroglycerin administration did not alter uterine contractility, despite significant changes in blood pressure. In contrast, indomethacin decreased electromyographic results to 70% of baseline after 1 hour and 47% after 2 hours. In pregnant ewes nitric oxide synthase inhibition failed to alter uterine contractility in response to oxytocin. These findings are in contrast to results of the in vitro study in which nitric oxide was shown to relax sheep myometrium. Conclusion: The absence of significant effects of nitric oxide synthase inhibition and nitric oxide donors on uterine contractility in vivo suggests that nitric oxide does not play a physiologic role in the regulation of uterine contractility in nonpregnant or pregnant ewes. (Am J Obstet Gynecol 2000;183:191-8.)

Sperm transport in the human female genital tract and its modulation by oxytocin as assessed by hysterosalpingoscintigraphy, hysterotonography, electrohysterography and Doppler sonography.

The transport function of the uterus and oviducts and its modulation by oxytocin has been examined using hysterosalpingoscintigraphy, recording of intrauterine pressure, electrohysterography and Doppler sonography of the Fallopian tubes. After application to the posterior vaginal fornix, a rapid (within minutes) uptake of the labelled particles into the uterus was observed during the follicular and during the luteal phase of the cycle in all patients. Transport into the oviducts, however, could only be demonstrated during the follicular phase. Transport was directed predominantly into the tube ipsilateral to the ovary bearing the dominant follicle; the contralateral oviduct appeared to be functionally closed. The proportion of patients exhibiting ipsilateral transport did increase concomitant with the increase of the diameter of the dominant follicle. That ipsilateral transport has biological significance is suggested by the observation that the pregnancy rate following spontaneous intercourse or insemination was significantly higher in those women in whom ipsilateral transport could be demonstrated than in those who failed to exhibit lateralization. Oxytocin administration was followed by a dramatic increase in the amount of material transported to the ipsilateral tube, as demonstrated by radionuclide imaging and by Doppler sonography following instillation of ultrasound contrast medium. Continuous recording of intrauterine pressure before and after oxytocin administration did show an increase in basal tonus and amplitude of contractions and a reversal of the pressure gradient from a fundo-cervical to a cervico-fundal direction. These actions of oxytocin were accompanied by an increase in amplitude of potentials recorded by electrohysterography. These data support the view that uterus and Fallopian tubes represent a functional unit that is acting as a peristaltic pump and that the increasing activity of this pump during the follicular phase of the menstrual cycle is reflected by an increased transport into the oviduct ipsilateral to the ovary bearing the dominant follicle. In addition, they strongly suggest a critical role of oxytocin in this process. Failure of this mechanism appears to be a cause of subfertility or infertility, as indicated by the low pregnancy rate following intrauterine insemination or normal intercourse in the presence of patent Fallopian tubes. It may be regarded as a new nosological entity for which we propose the term tubal transport disorder (TTD). Since pregnancy rate of such patients is normal when treated with in-vitro fertilization (IVF), hysterosalpingoscintigraphy seems to be useful for the choice of treatment modalities in patients with patent Fallopian tubes suffering from infertility.

The in vivo relationship between blood flow, contractions, pH and metabolites in the rat uterus.

Little is known about the relationship between smooth muscle contractile activity and its blood supply. We have therefore investigated this in the rat uterus, using laser-Doppler flow measurement and intra-uterine pressure recordings. We found an inverse linear relationship between flow and contractile activity. There was no evidence for a critical level of flow, above which function is maintained and below which it declines; even small reductions in blood flow decreased uterine force. Force was rapidly restored upon reperfusion. Reactive hyperaemia was absent from all but 6 of the 41 preparations studied. We used 31P nuclear magnetic resonance (NMR) spectroscopy to measure concentrations of adenosine triphosphate (ATP), phosphocreatine (PCr), inorganic phosphate (Pi) and intracellular pH (pHi) simultaneously with force and flow. Reductions in flow were associated with significant reductions in [ATP], [PCr] and pHi, and an increase in [Pi]. These changes were related to flow significantly and linearly and their effects on force may be additive. These data show that uterine smooth muscle is closely dependent upon its blood supply for maintaining both normal force production and metabolite levels. Consequently, even small decrements in flow may have deleterious functional effects.

Assessment of Uterine Contractions (UC) by Simultaneous Recording of Intrauterine Pressure and Uterine Ultrasound Imaging

Assessment of Uterine Contractions (UC) by Simultaneous Recording of Intrauterine Pressure and Uterine Ultrasound Imaging

O-152 Assessment of uterine contractions (UC) by simultaneous recording of intrauterine pressure and uterine ultrasound imaging

O-152 Assessment of uterine contractions (UC) by simultaneous recording of intrauterine pressure and uterine ultrasound imaging

Recording and analysis of uterine activity in pregnant guinea-pigs.

Guinea-pigs are of considerable interest for the study of the physiology of parturition in view of their lack of placental 17-alpha hydroxylase, a property which they share with Man and monkeys. To allow long-term analysis of uterine activity, a chronic guinea pig model was developed carrying a uterine electromyogram (EMG) electrode array, intrauterine and intraabdominal balloon catheters and vascular catheters. Operative procedures and the characteristics of the hardware and software are described and evaluated. Quantitative analysis of uterine activity relies on the quasi-integrated EMG signal which is highly correlated with the raw EMG signal. Under optimal conditions of intrauterine pressure recording, the area of the quasi-integrated EMG signal is highly correlated with the area of the intrauterine pressure increment. The preparation is stable for at least four weeks, measurements are reproducible, and biologically meaningful results are obtained from the recordings.

Intrauterine Pressure During Abdominal Hysterectomy

Many studies indicate that the process of surgical resection of a tumor may lead to vascular spread of malignant cells. To decrease the pressure in the tumorous mass, and hence the risk of spread, no-touch techniques have been developed and implemented in many fields. In an effort to investigate the degree to which surgical manipulation during hysterectomy altered intrauterine pressure, six patients undergoing hysterectomy for benign conditions were studied. Continuous intrauterine pressure recordings indicate that significant static and transient pressures are created. Pressures observed varied from a high of 314 mm Hg (during cardinal ligament dissection) to a low of 2 mm Hg. There appears to be an increase in the likelihood of elevated pressure as the dissection progresses down the uterus, with an overall average of 43 mm Hg during broad ligament dissection versus 68 mm Hg average during bladder dissection. Pressures seem to fluctuate less as the level of operator experience increases. The significance of these findings in the possible spread of malignant cells is unknown. (J GYNECOL SURG 7:17, 1991)

The physiological and clinical effects of progesterone inhibition with mifepristone (RU 486) in the second trimester

A double-blind placebo-controlled trial was performed in 20 primigravidae to assess the physiological and clinical effects of oral mifepristone on myometrial contractility and sensitivity in the second trimester. Ten women received 600 mg of oral mifepristone and 10 women a placebo 24 h before abortion was induced in both groups, with extra-amniotic PGE2 instillation. Intrauterine pressure recordings demonstrated increased spontaneous uterine activity and increased sensitivity to PGE2 and ergometrine, but no change in oxytocin sensitivity after mifepristone treatment. There were no significant differences in PGE or PGF metabolite concentrations in peripheral maternal plasma over the 24-h study period after treatment between the mifepristone and placebo groups. The mean induction abortion interval in the mifepristone group was 512 (SD 321) min compared with 1128 (SD 606) min in the placebo group (P less than or equal to 0.02). The mechanism whereby mifepristone provokes enhanced uterine contractility and sensitivity to prostaglandins, with a reduction in abortion times, does not appear to be through endogenous production of PGE or PGF.

Power spectrum analysis of myometrial electromyogram and intrauterine pressure changes in the pregnant rhesus monkey in late gestation

Various methods have been used to quantify myometrial activity in the pregnant rhesus monkey during the last third of gestation. A precise definition of activity must retain the characteristics of epoch duration, amplitude, and the repetitive frequencies of active epochs. We used Fast Fourier Transform and power spectrum analysis to determine whether the patterns of myometrial contractility consist predominantly of contractions or contractures. This analysis allows quantification of activity represented by each of these patterns of activity. We applied these methods to myometrial electromyogram and intrauterine pressure recordings in pregnant rhesus monkeys to characterize the changes in myometrial activity that occur after surgery, after intravenous indomethacin administration, and when food is withdrawn for 48 hours. We conclude that changes in the frequency pattern of myometrial activity provide important information in relation to labor and delivery contractions.

The influence of a combined oral contraceptive on uterine activity and reactivity to agonists in primary dysmenorrhea.

The mechanisms underlying the therapeutic effect of an oral contraceptive (150 micrograms levonorgestrel and 30 micrograms ethinyl estradiol daily for 21 days) in primary dysmenorrhea were studied by recordings of uterine activity and reactivity to lysine (L) vasopressin (VP) and prostaglandin (PG) F2 alpha on the first day of menstruation in 14 women before and after one period of oral contraceptive treatment. During the first session, when all women had moderate to severe dysmenorrhea, intra-uterine pressure recording showed an intensive uterine activity, and bolus injections of LVP (6 pmol/kg body weight; 6 subjects) or PGF2 alpha (6 or 12 nmol/kg body weight; 4 subjects in each group) increased contractile activity and discomfort. After oral contraceptive treatment, spontaneous uterine activity, measured as total pressure area, decreased significantly (p = 0.02 and p = 0.03 in the VP and PG groups, respectively). The mean uterine responses to LVP and PGF2 alpha were on average smaller after oral contraceptive treatment and the women experienced minimal discomfort after this injection. It is suggested that inhibition of uterine activity could be an important mechanism for the therapeutic effect of gestagen-dominated oral contraceptives in primary dysmenorrhea and that reduced uterine reactivity to agonists might contribute to this effect.

Uterine blood flow and myometrial activity at menstruation, and the action of vasopressin and a synthetic antagonist.

Local endometrial blood flow was measured by a thermistor technique and myometrial activity by intrauterine pressure recording in 10 women before and during menstruation. The effect of lysine vasopressin infusion (1 pmol/kg body-weight per min) and of bolus injection of a synthetic oxytocin analogue, 1-deamino-2-D-Tyr(OEt)-4-Thr-8-Orn-oxytocin (10 nmol/kg body-weight), were studied. Spontaneous variations in blood flow were seen synchronous with clearly demarcated uterine contractions, the myometrial activity being significantly increased in early (day -1 to day +2) compared with late (day +3 to day +5) menstrual phase. The vasopressin infusion decreased blood flow, stimulated uterine activity and caused slight to moderate dysmenorrhoea-like pain. These effects were completely inhibited by the injection of the oxytocin analogue. In-vitro studies on uterine arteries confirmed that the analogue also inhibited the vasopressin-induced constriction of the uterine arteries. This antagonist was more effective than two other analogues, 1-deamino-2-D-Tyr(OEt)-4-Val-8-Orn-oxytocin and 1-deamino-2-Tyr(OEt)-oxytocin. The counteracting effect of 1-deamino-2-D-Tyr(OEt)-4-Thr-8-Orn-oxytocin on the vasopressin-induced decrease of blood flow and increase of contractions supports the therapeutic value of the drug in primary dysmenorrhoea and preterm labour.