Human Uterine Contractility Research Articles

383: Human uterine contractility at term in relation to parity

It is well described that parous women perform better in labor than primigravid women, with less dystocic labour, shorter durations of labor and lower cesarean rates. There are no published data to our knowledge, comparing myometrial contractile parameters of nulliparous with parous women. Our study aim was to examine certain parameters in human myometrial tissue, and compare the results between the following 3 groups: Primigravid women (P0); Women with 1 previous delivery (P1); Women with more than 1 previous delivery (P>1); to determine if there was any difference between the contractile performance of each group. Myometrial biopsies were obtained at cesarean delivery (CD), at term, from n=74 women, with Institutional Ethical Review Board approval, Galway University Hospital. Each biopsy was dissected into 8 strips and suspended for in vitro tissue baths under physiological conditions, as previously described [1], giving a total of 592 samples. The following parameters of contractile performance were measured for spontaneous contractions: maximal amplitude (MAMP), mean contractile force (MCF), time to maximal amplitude, maximum rate of rise, frequency and occurrence of simple and complex (biphasic and multiphasic) contractions. Comparisons were made across the 3 groups: P0 n=14; P1 n=37; P>1 n=23. Statistical analysis was performed using T-Test Assuming Unequal Variance. The results obtained for the contractile parameters, for the 3 groups, are shown in Table 1. The MCF was greater for myometrial contractions in parous women (PO V P1 P=0.0061; P1 V P>1 P= 0.00089). Women P>1 displayed a shorter time to onset of first contraction (P=0.00046). For parous women there was a slower rate of rise and slower rate of relaxation. No difference was observed in any of the other parameters. (Table 2) These results suggest that there is an inherent biological difference between the contractile parameters of human myometrium in the third trimester, between primigravid and parous women. These findings correlate with clinical observations that parous women have more efficient and shorter labours. The increased force of contractions observed with parity, highlights the need for caution in these women undergoing augmentation of labor.

584: Human uterine contractility at term in relation to previous cesarean section

The efficiency of myometrial contractility in labor, for the woman who have had a previous cesarean delivery (CD), is an important factor for women undergoing trial of labor after a cesarean. There are no data, to our knowledge, on this topic. The aim of this study was to examine a range of contractile parameters in human myometrial tissue in vitro, and compare the results obtained between the following 3 groups: Women with no previous CD (CD=0); Women with 1 previous CD (CD=1); Women with greater than one CD (CD=>1). Myometrial biopsies were obtained at CD, performed at term, from n=74 women, with Institutional Ethical Review Board approval, Galway University Hospital. Myometrial strips were dissected into 8 uniform samples, and suspended for in vitro tissue bath analysis under physiological conditions, as previously described [1]. The following parameters of contractile performance for spontaneous contractions were measured: maximal amplitude (MAMP), mean contractile force (MCF), time to maximal amplitude, maximum rate of rise, frequency and occurrence of simple and complex (biphasic and multiphasic) contractions. Comparisons were made across the 3 groups as follows: CD=0 n=22; CD=1 n=37; CD=>1 n=15. Statistical analysis was performed using T-Test Assuming Unequal Variance. The results obtained for the different contractile parameters, for the 3 groups, are shown in Table 1. 592 tissue samples were analysed from 74 women. The only significant difference (Table 2) in contractile parameters found was in the frequency of contractions, with a lower frequency of contractions in the CD=1 group compared to CD=0 and CD=>1 groups (p=6.36E-06 and p=0.000135 respectively). These data indicate that there is no significant difference in the general biological characteristics of human uterine contractions in vitro, in women who have had one, or greater that one previous CD, in comparison to women who have had none. The only notable feature is that the frequency of contractions was greater in the sub-group of women who had one previous CD. These findings indicate that factors other than the functional contractility of uterine tissue, may be responsible for the increased CD rate observed among women undergoing VBAC.

Magnetically Bioprinted Human Myometrial 3D Cell Rings as A Model for Uterine Contractility.

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 bioprinted into rings in 384-well formats for throughput uterine contractility analysis. The bioprinted uterine rings from various cell origins and patients show different patterns of contractility and respond differently to clinically relevant uterine contractility inhibitors, indomethacin and nifedipine. We believe that the novel system will serve as a useful tool to evaluate the physiology of human parturition while enabling high-throughput testing of multiple agents and conditions.

Maternal body mass index and spontaneous contractility of human myometrium in pregnancy.

There is controversy as to whether maternal body mass index (BMI) influences the contractility of human myometrium in pregnancy. The aim of this study was to examine spontaneous contractile activity of human pregnant myometrium in vitro, with respect to maternal BMI. Myometrial tissue specimens were obtained at cesarean delivery from 74 women with BMI values ranging from 19 to 50.1 kg m-2. By recording in vitro from eight strips per donor (590 strips in total), several parameters of spontaneous contractile activity were monitored. The relationship between BMI and contractility was evaluated using linear regression analysis. There was a significant correlation between maximum amplitude (P=0.007) and mean contractile force (P=0.001) with increasing BMI. However, the time to onset of contractions (P=0.009), and time taken to reach maximal amplitude (P=0.020) also increased with increasing BMI. No significant correlation was observed with BMI for other parameters studied. The mean maximum amplitude value for spontaneous contractions was 37±1 mN, the mean contractile force for spontaneous contractions was 4.1±0.1 mN, the average time to the first spontaneous contraction was 11.3±0.6 min and the average frequency of contractions was 6.5±0.2 per hour. These results suggest that the time to onset of contractions is increased with increasing maternal BMI, but that the force developed is greater. In all other respects, human uterine contractility is unaffected by increasing BMI. These findings underline the complexity of regulation of uterine contractility in labor with elevated maternal BMI.

Paeoniflorin, a novel heat-shock protein inducing compound, and human myometrial contractility in vitro.

Heat shock proteins (HSPs) are synthesized in virtually all organisms in response to increases in temperature. They are associated with a relaxant effect on the human myometrium and are present in decreased concentration in the myometrium at the time of labor. Paeoniflorin is derived from Paeonia lactiflora and has been shown to induce the synthesis of HSPs in cultured mammalian cells. The purpose of the study was to evaluate the effect of paeoniflorin on human uterine contractility. Samples of human myometrium were taken at lower segment cesarean section. Dissected muscle strips were suspended under isometric conditions and exposed to cumulative additions of paeoniflorin in concentrations ranging from 1 nmol/L to 10 mol/L. Control experiments were simultaneously performed. Paeoniflorin was found to exert an inhibitory effect on spontaneous and agonist-induced contractions compared to control strips. The mean maximal inhibition values were: 42.21% ± 9.26 for spontaneous contractions (n = 6; P < 0.0001) and 47.84% ± 9.05 for oxytocin-induced contractions (n = 6; P < 0.0001). The HSP inducing compound, paeoniflorin, had a relaxant effect on human uterine contractility in vitro. These results reinforce the fact that HSPs may play a physiological role in the onset of labor and may also provide future targets for novel tocolytic treatments.

Structure-based lead discovery for protein kinase C zeta inhibitor design by exploiting kinase-inhibitor complex crystal structure data and potential therapeutics for preterm labour.

The protein kinase C (PKC) is a family of serine/threonine kinases with a broad range of cellular targets. Members of the PKC family participate at the diverse biological events involved in cellular proliferation, differentiation and survival. The PKC isoform zeta (PKCζ) is an atypical member that has recently been found to play an essential role in promoting human uterine contractility and thus been raised as a new target for treating preterm labour and other tocolytic diseases. In this study, an integrative protocol was described to graft hundreds of inhibitor ligands from their complex crystal structures with cognate kinases into the active pocket of PKCζ and, based on the modeled structures, to evaluate the binding strength of these inhibitors to the non-cognate PKCζ receptor by using a consensus scoring strategy. A total of 32 inhibitors with top score were compiled, and eight out of them were tested for inhibitory potency against PKCζ. Consequently, five compounds, i.e. CDK6 inhibitor fisetin, PIM1 inhibitor myricetin, CDK9 inhibitor flavopiridol and PknB inhibitor mitoxantrone as well as the promiscuous kinase inhibitor staurosporine showed high or moderate inhibitory activity on PKCζ, with IC50 values of 58±9, 1.7±0.4, 108±17, 280±47 and 0.019±0.004μM, respectively, while other three compounds, including two marketed drugs dasatinib and sunitinib as well as the Rho inhibitor fasudil, have not been detected to possess observable activity. Next, based on the modeled structure data we modified three flavonoid kinase inhibitors, i.e. fisetin, myricetin and flavopiridol, to generate a number of more potential molecular entities, two of which were found to have a moderately improved activity as compared to their parent compounds.

Leukotriene receptor antagonist as a novel tocolytic in an in vitro model of human uterine contractility

ObjectiveThis study analyzed the ability of montelukast, a cysteinyl-leukotrienes receptor antagonist and anti-inflammatory agent, to produce a consistent tocolytic effect alone or in combination with nifedipine, a calcium (Ca2+) channel blocker currently used in clinical practice. Study designUterine biopsies were obtained from consenting women undergoing elective cesarean sections at term (n=20). Myometrial microsomal fractions were analyzed by immunoblotting to quantify relative cysteinyl leukotrienes receptor 1 (CysLTR1) levels. Isometric tension measurements were performed in vitro on human myometrial strips (n=120) in isolated organ baths in order to establish concentration–response curves to montelukast and to quantify changes in Ca2+ sensitivity on β-escin permeabilized tissues. ResultsImmunodetection analysis revealed the presence of CysLTR1 receptor in uterine tissues, fetal membranes and placenta. A significant increase in area under the curve (AUC) was quantified following the addition of leukotriene D4 (LTD4) (0.01–0.3μM), an end-product of the lipoxygenase pathway. Conversely, addition of montelukast produced a significant tocolytic effect by decreasing the frequency and AUC (IC50=1μM). Moreover, addition of montelukast also resulted in a reduced Ca2+ sensitivity as compared to control tissues (EC50 values of 654 and 403nM; p=0.02 at pCa 6), while an additive effect was observed in combination with 0.1nM nifedipine (p=0.004). ConclusionThis original study demonstrates the potency of montelukast as a tocolytic agent in an in vitro human uterine model. Montelukast, in combination with nifedipine, could represent a therapeutic approach to reduce inflammation associated with prematurity while facilitating the inhibition of preterm labor.

743: Pharmacological blockade of anoctamin-1 on human pregnant uterine smooth muscle attenuates oxytocin induced muscle force and pacing frequency

Anoctamins are a group of calcium-activated chloride channels that play a role in the pacing of intestinal smooth muscle, and which can be identified in myometrial cells. The goal was to assess the ability of tannic acid, an anoctamin-1 antagonist, to suppress intact human uterine smooth muscle cell contractility

Anthrax toxin receptor 2 promotes human uterine smooth muscle cell viability, migration and contractility

Previously we demonstrated anthrax toxin receptor 2 knockout (Antxr2(-/-)) mice are fertile but fail to deliver their pups at term. This parturition defect is associated with overaccumulation of extracellular matrix proteins and decreased myometrial cell content in the uterus. Myometrial cell loss in Antxr2(-/-) uterine tissue prompted us to evaluate if ANTXR2 is essential for human uterine smooth muscle cell viability and function. We subjected human uterine smooth muscle cell to lentiviral-mediated knock down or retroviral-mediated overexpression of ANTXR2. Flow cytometry confirmed lentiviral-mediated knock down or retroviral-mediated overexpression in cell lines vs control. Cell behavior and function in control, lentiviral-mediated knock down and retroviral-mediated overexpression cells were evaluated for apoptosis via TUNEL assay, migration via Boyden chamber assay and with oxytocin-mediated collagen contraction assays. Matrix metalloproteinase activity was evaluated using gelatin zymography. Cell lines and samples were run in duplicate. Student t test was used for statistical analysis. ANTXR2 is expressed by human uterine smooth muscle cell. Human uterine smooth muscle cell-lentiviral-mediated knock down cells exhibited increased apoptosis (P < .05) and decreased migration (P < .05), although human uterine smooth muscle cell-retroviral-mediated overexpression cells exhibited no change in apoptosis (P = .91) and increased migration (P = .05) vs control. Human uterine smooth muscle cell-lentiviral-mediated knock down cells contracted significantly less than control, although human uterine smooth muscle cell-retroviral-mediated overexpression cells showed no difference in contractility vs control. Matrix metalloproteinase activity 2 activity appeared slightly decreased in human uterine smooth muscle cell-lentiviral-mediated knock down cells and increased in human uterine smooth muscle cell-retroviral-mediated overexpression cells vs control. ANTXR2 is expressed by human uterine smooth muscle cell and appears important for normal human uterine smooth muscle cell viability, migration and contractility. Further studies are needed to delineate if ANTXR2 is important for normal and abnormal labor patterns.

528: Leukotriene receptor antagonist as a novel tocolytic in an in vitro model of human uterine contractility for preventing preterm labor

twin pregnancies who delivered in New York City from 2003-2012. One cohort (n 532) was managed by a single maternal-fetal medicine practice and delivered at one large academic medical center. This cohort underwent routine CL screening every 2-3 weeks starting at 16 weeks and fFN screening every 2-3 weeks beginning at 22 weeks. The second cohort (n 456) were all twin pregnancies delivered at a second large academic center. The second cohort did not undergo routine CL and fFN screening and only had these tests done as clinically indicated. Outcomes measured include cerclage placement, PTB, spontaneous PTB (SPTB), and antenatal corticosteroid (ACS) exposure. RESULTS: Rates of cerclage placement, PTB, and SPTB were similar between the two groups (Table). However, routine screening using CL and fFN was associated with improved rates of ACS exposure in women who delivered 34 weeks and 34-36 6/7 weeks, without an increased ACS exposure in women who delivered at term. CONCLUSION: In twin pregnancies, routine CL and fFN screening does not reduce the risk of PTB or SPTB. However, the routine use of these tests significantly improves ACS exposure for women who deliver preterm without significantly increasing ACS exposure to women who deliver at term.

CRH Activation of Different Signaling Pathways Results in Differential Calcium Signaling in Human Pregnant Myometrium before and during Labor

Our previous study has demonstrated that CRH has differential effects on human uterine contractility before and after onset of labor. Intracellular Ca2+ concentration ([Ca2+]i) mobilization plays an important role in the control of uterine contraction. Our objective was to investigate the effects of CRH on [Ca2+]i homeostasis in laboring and nonlaboring myometrial cells and determine subsequent signaling involved in [Ca2+]i regulation by CRH. The myometrial tissues were obtained from pregnant women who were undergoing or not undergoing labor at term. [Ca2+]i was determined by Ca2+ imaging system using the fluorescent dye fura-2-acetoxymethyl ester. Western blot analysis, ELISA, and RIA were used to determine the signaling pathways induced by CRH. CRH induced Ca2+ transient in laboring cells, which was blocked by CRH receptor type 1 (CRHR1) antagonist antalarmin. CRHR1 knockdown impaired this effect of CRH. CRH activated Gi protein, decreased cAMP production, and induced phosphorylated phospholipase C-β3 and inositol-1,4,5-triphosphate production. Phospholipase C and inositol-1,4,5-triphosphate receptor inhibitors blocked the CRH-induced Ca2+ transient in laboring cells. CRH did not induce whereas antalarmin induced the Ca2+ transient in nonlaboring cells. Knockdown of CRHR1 impaired the effect of antalarmin. CRH acted on CRHR1 to activate Gs in nonlaboring cells. Forskolin blocked antalarmin-induced Ca2+ transient. CRH acts on CRHR1 to activate different signaling pathways before and after onset of labor, thereby resulting in differential calcium signaling in response to CRH. The signaling pathways of CRHR1 might serve as a target for the development of new therapeutic strategies for preterm birth.

Metformin and human uterine contractility

Metformin and human uterine contractility

The adipokine apelin and human uterine contractility

Obesity is an increasing problem in obstetric practice. Apelin, secreted by adipocytes, is present in increased serum concentrations in an obese state. Our group has previously highlighted that the adipokines leptin and ghrelin have a potential role in metabolic modulation of uterine contractility in obese women. The aim of this study was to evaluate the effects of apelin on human uterine contractility in vitro. Biopsies of human myometrium were obtained at elective cesarean section. Myometrial strips suspended under isometric conditions, undergoing spontaneous and oxytocin-induced contractions, were exposed to cumulative additions of apelin in the concentration range of 1 nmol/L to 1 μmol/L. Control experiments were performed simultaneously. Apelin exerted an inhibitory effect on spontaneous and oxytocin induced contractions in human myometrium. The mean maximal inhibition values were 36.8 ± 6.4% for spontaneous (n = 6; P = .002) and 30.4 ± 4.6% for oxytocin-induced contractions (n = 6; P < .0001). Apelin inhibits human uterine contractility in vitro, raising the possibility that such metabolic modulation may play a physiological role in obese parturients.

Relaxant effect of Levosimendan on human uterine contractility in vitro

Levosimendan, a compound that exerts effects on calcium sensitivity and intracellular free calcium, in addition to opening ATP-sensitive K-channels, is widely used in the treatment of heart failure. Because of its dual mechanism of action, we hypothesized that it would modulate human uterine contractility. Biopsies of human myometrium were obtained at elective cesarean section (n = 16). Dissected myometrial strips suspended under isometric conditions, undergoing spontaneous and oxytocin-induced contractions, were exposed to cumulative additions of levosimendan in the concentration range of 1 nmol/L to 100 mmol/L. In separate experiments, the effects of prior exposure to the K-ATP antagonist glibenclmide (100 mmol) on the effects of levosimendan on myometrial contractility were evaluated. Simultaneous controls were performed for all experiments. Levosimendan exerted an inhibitory effect on spontaneous and agonist induced contractions, when compared with control strips. The mean maximal inhibition (MMI) values were as follows: 45.34% +/- 5.92% for spontaneous contractions (n = 6; P < .05), and 41.88% +/- 5.40% for oxytocin-induced contractions (n = 6; P < .05). The inhibitory effect of levosimendan was significantly antagonized by glibenclamide, resulting in the mean maximal inhibition for levosimendan reduced to 19.04% +/- 3.61% for spontaneous contractions (n = 6; P < .05), and 16.53% +/- 4.08% for oxytocin induced contractions (n = 6; P < .05). Levosimendan exerted a potent relaxant effect on spontaneous and agonist-induced human uterine contractility in vitro. This effect was reduced in the presence of K-ATP blockade. Because of the putative role of levosimendan in inflammatory conditions, the findings here may have implications for its future use as therapy for preterm labor.

17 alpha-hydroxyprogesterone caproate vehicle, castor oil, enhances the contractile effect of oxytocin in human myometrium in pregnancy

The possibility exists that the vehicle for 17-alpha-hydroxyprogesterone caproate, castor oil, exerts an effect on human uterine contractility. The aim of this study was to evaluate its effects on contractility of myometrial preparations that were obtained during pregnancy. Myometrial strips were suspended under isometric conditions. Contractility was induced with oxytocin. Strips were incubated in castor oil or physiologic salt solution and suspended for a further oxytocin challenge. Contractile integrals were compared between both groups. Strips that were exposed to castor oil demonstrated increased contractile activity that was elicited by oxytocin (mean contractility value, 165.53%+/-17.03%; n=8; P=.004), compared with control strips (mean contractility value, 72.57%+/-7.48%; n=8; P=.003). There was a significant increase in contractile activity of the castor oil-exposed strips, compared with those that were exposed to physiologic salt solution (n=8; P<.001). Exposure of human myometrial preparations to castor oil results in enhanced oxytocin-induced contractility.

Effects of abnormal cannabidiol on oxytocin-induced myometrial contractility

The objective of this study was to investigate the effects of abnormal cannabidiol (abn-cbd) on oxytocin-induced myometrial contractility occurring during pregnancy. Isometric tension recordings were performed in isolated myometrial strips from biopsies obtained at elective cesarean section. The effects of cumulative doses of abn-cbd (10(-9)-10(-5) M) on oxytocin-induced myometrial contractions alone, and on those following pre-incubation with SR 144528, AM 251, methylene blue, and iberiotoxin were measured, and dose-response curves were constructed. The pD(2) (-log EC(50)) values and the maximal inhibitory (MMI) values that were achieved were compared for each tissue type. Abn-cbd exerted a potent relaxant effect on oxytocin-induced myometrial contractions in vitro. Pre-incubation with the guanylate cyclase inhibitor, methylene blue, and the BK(Ca) channel antagonist, iberiotoxin, significantly attenuated this effect (for pD(2), P<0.01; for MMI, P<0.01). Abn-cbd exerts a potent inhibitory effect on human uterine contractility. This effect is partially mediated through modulation of guanylate cyclase and activation of BK(Ca) channel activity. These findings have implications for physiologic regulation of myometrial quiescence.

486: Paeoniflorin, a novel heat shock protein inducing compound, and human uterine contractility

486: Paeoniflorin, a novel heat shock protein inducing compound, and human uterine contractility

214: The effect of metformin on human uterine contractility in vitro

Metformin is the most prescribed oral hypoglycaemic in the United States. In recent years metformin has been prescibed with increasing frequency for the treatment of gestational diabetes mellitus (GDM) as an alternative to subcutaneous insulin. It is known that metformin does cross the placenta however its effects on uterine function have been hitherto unexplored. The purpose of our study was to evaluate the effect of metformin on human uterine contractiolity in vitro.

Modulation of human uterine smooth muscle cell collagen contractility by thrombin, Y-27632, TNF alpha and indomethacin

BackgroundPreterm labour occurs in approximately 10% of pregnancies and is a major cause of infant morbidity and mortality. However, the pathways involved in regulating contractility in normal and preterm labour are not fully elucidated. Our aim was to utilise a human myometrial contractility model to investigate the effect of a number of uterine specific contractility agents in this system. Therefore, we investigated the contractile response of human primary uterine smooth muscle cells or immortalised myometrial smooth muscle cells cultured within collagen lattices, to known mediators of uterine contractility, which included thrombin, the ROCK-1 inhibitor Y-27632, tumour necrosis factor alpha (TNF alpha) and the non-steroidal anti-inflammatory indomethacin.MethodsCell contractility was calculated over time, with the collagen gel contraction assay, utilising human primary uterine smooth muscle cells (hUtSMCs) and immortalised myometrial smooth muscle cells (hTERT-HM): a decrease in collagen gel area equated to an increase in contractility. RNA was isolated from collagen embedded cells and gene expression changes were analysed by real time fluorescence reverse transcription polymerase chain reaction. Scanning electron and fluorescence microscopy were employed to observe cell morphology and cell collagen gel interactions. Statistical analysis was performed using ANOVA followed by Tukey's post hoc tests.ResultsTNF alpha increased collagen contractility in comparison to the un-stimulated collagen embedded hUtSMC cells, which was inhibited by indomethacin, while indomethacin alone significantly inhibited contraction. Thrombin augmented the contractility of uterine smooth muscle cell and hTERT-HM collagen gels, this effect was inhibited by the thrombin specific inhibitor, hirudin. Y-27632 decreased both basal and thrombin-induced collagen contractility in the hTERT-HM embedded gels. mRNA expression of the thrombin receptor, F2R was up-regulated in hUtSMCs isolated from collagen gel lattices, following thrombin-stimulated contractility.ConclusionTNF alpha and thrombin increased uterine smooth muscle cell collagen contractility while indomethacin had the opposite effect. Thrombin-induced collagen contractility resulted in F2R activation which may in part be mediated by the ROCK-1 pathway. This study established the in vitro human myometrial model as a viable method to assess the effects of a range of uterotonic or uterorelaxant agents on contractility, and also permits investigation of the complex regulatory pathways involved in mediating myometrial contractility at labour.

In Vitro Effects of Propofol on Gravid Human Myometrium

The aim of this study was to evaluate the direct effect of propofol (di-isopropyl phenol) on the contractile properties of gravid human uterine muscle. Six specimens of uterine muscle were obtained from term parturients undergoing elective lower segment caesarean section. Small strips (1 x 2 x 12 mm) of muscle were prepared and suspended in an organ bath containing oxygenated Kreb's solution at 36.5 degrees C. Following preparation, spontaneous regular contractions developed at a rate of one contraction every six to 10 minutes. Force of contraction was recorded continuously using an isometric tension transducer Following baseline measurements, propofol was introduced into the bath at concentrations corresponding to 2 microg/ml, 5 mcirog/ml and 8 mirog/ml. The specimens were also exposed to intralipid in concentrations equivalent to that found in the 8 microg/ml solution of propofol to determine whether this additive influenced uterine contractility. Contractility (defined as area under the tension/time curve) was decreased to 89 +/- 6.5% of control at 2 microg/ml, 53 +/- 4.3% at 5 microg/ml and 45 +/- 4.1% at 8 microg/ml. This decrease in contractility was statistically significant at concentrations >2 microg/ml. Intralipid did not significantly affect uterine contractility. The results of this study show that propofol decreases isolated human uterine muscle contractility in a dose-dependent manner