Frequency Of Myometrial Contractions Research Articles

Effect of magnesium sulfate on oxytocin-induced contractility in human myometrium: an in vitro study.

The purpose of this study was to determine the contractile patterns induced by oxytocin in myometrium exposed to magnesium sulfate (MgSO4). We hypothesized that MgSO4 pretreatment would reduce oxytocin-induced myometrial contractions in both oxytocin-naïve and oxytocin-desensitized myometrium. In this prospective in vitro study, myometrial samples were obtained from 26 women undergoing elective Cesarean deliveries. Samples were divided into six groups. Four groups were apportioned to no pretreatment (control group), oxytocin 10-5 M pretreatment (desensitization group), MgSO4 3.5 mM pretreatment, and MgSO4 3.5 mM + oxytocin 10-5M pretreatment. This was followed by dose-response testing to oxytocin 10-10 to 10-5M in all four groups. Two additional groups included MgSO4 3.5 mM pretreatment and MgSO4 3.5 mM + oxytocin 10-5 M pretreatment, followed by dose-response testing to oxytocin along with MgSO4 3.5 mM. The outcomes were motility index (MI), as defined by the amplitude (g) × frequency of myometrial contractions (c) over ten minutes, and area under the curve (AUC). In oxytocin-naïve myometrium, the mean (standard error [SE]) MI was not affected by MgSO4 pretreatment [3.31 (0.20) √g⋅c/10 min] as compared with control (P = 0.88), even when MgSO4 was continued during dose-response testing [2.50 (0.19) √g⋅c/10 min; P = 0.41]. In the oxytocin-desensitized model, mean (SE) MI was not affected by MgSO4 pretreatment [2.60 (0.21) √g⋅c/10 min; P = 0.68], but when MgSO4 was continued during the dose-response period, the MI was significantly reduced compared with control [1.89 (0.13) √g⋅c/10 min; P < 0.001]. The results for AUC were similar to MI, except for a significant reduction in oxytocin-naïve myometrium when MgSO4 was continued during dose-response testing (P = 0.02). Magnesium sulfate pretreatment does not impair oxytocin-induced myometrial contractility in oxytocin-naïve or desensitized myometrium unless it is continued during oxytocin dose-response testing. These results suggest that its tocolytic effect is likely dependent on an extracellular mechanism. The study was registered with ClinicalTrials.gov, number NCT02647268.

Investigating the effects of the Rho-kinase enzyme inhibitors AS1892802 and fasudil hydrochloride on the contractions of isolated pregnant rat myometrium

ObjectivesRho-kinases (ROCKs), are one of the dynamic structures of the actin cytoskeleton and they mediate different biological processes, including regulation of calcium sensitivity of smooth muscle contraction. The activation of Rho A/ROCK system is thought to be effective on the termination time of the pregnancy process. The aim of this study, was to investigate in vitro effects of the ROCK enzyme inhibitors, clinically available fasudil hydrochloride, and a new promising inhibitor AS1892802, on the contractions of isolated pregnant rat myometrium. Study designTerm pregnant Wistar albino rats (n=12), weighing 200–220g, were used in this study. Myometrial tissues obtained from rats were dissected into four full-thickness longitudinal muscle strips and then myometrial tension was recorded isometrically. The inhibitory effects of cumulative concentrations of AS1892802 and of fasudil hydrochloride in the presence and absence of ODQ (guanylate cyclase inhibitor), l-NAME (nitric oxide synthase inhibitor) and l-NNA (endothelial nitric oxide synthase inhibitor) on oxytocin-induced myometrial contractions were measured, and values for −log10EC50 (pD2) and mean maximal inhibition (Emax) were compared. ResultsBoth ROCK inhibitors, AS1892802 and fasudil hydrochloride starting from the concentrations of 10−6M reached statistical significance on contraction amplitude and frequency of myometrial strips (p<0.05). The inhibition of the amplitude and frequency of myometrial contractions was antagonized with ODQ (10−5M; only amplitude), l-NAME (3×10−5M) and l-NNA (10−5M) (p<0.05). ConclusionThese results suggest that fasudil hydrochloride and AS1892802 may contribute to the development of new tocolytic drugs. We conclude that AS1892802 and fasudil hydrochloride perform this inhibitory effect partially through ROCK inhibition and the NO/cGMP pathway.

Orai1 protein expression and the role of calcium release-activated calcium channels in the contraction of human term-pregnant and non-pregnant myometrium.

This experimental in vitro study examined differences in the expression and activity of calcium release-activated calcium (CRAC) channels of human term-pregnant and non-pregnant myometrium. The tissue samples were obtained from term-pregnant myometrium in labor of women undergoing cesarean section and from non-pregnant myometrium of women undergoing total hysterectomy due to uterine myoma. The expression of Orai1 protein, a pore-forming subunit of CRAC channels, in human myometrium was examined using immunohistochemistry. CRAC channel involvement in the amplitude and frequency of myometrial contractions was evaluated in vitro using a tissue bath method with a CRAC ion channel blocker 3-fluropyridine-4-carboxylic acid (FPCA). Decreased Orai1 expression was observed in human term-pregnant laboring myometrium compared with non-pregnant myometrium. However, the initial oxytocin-induced contraction of myometrium was significantly suppressed at different doses of FPCA in both non-pregnant human isolated myometrium and non-pregnant myometrium. The frequency of contractions was the most significantly reduced at the lowest dose of FPCA in non-pregnant myometrium and remained suppressed at all doses of FPCA in term-pregnant myometrium. Salbutamol was shown as more effective in suppression of amplitude in term-pregnant isolated myometrium. Our results provide the first information about the changes in the Orai1 protein expression and activity of human myometrial CRAC channels in term-pregnant laboring myometrium.

Outcomes of gestation length in relation to farrowing performance in sows and daily weight gain and metabolic profiles in piglets

The objective of this study was to evaluate uterine activity at farrowing in sows with different gestation lengths (GL), and its effect on the metabolic profile, blood gases and daily weight gain of neonate piglets. The experiment covered a period of 25 weeks and involved 200 Yorkshire-Landrace sows. The animals were assigned to four groups of 50 sows each and distributed according to GL, as follows: GL1: 107–109 days; GL2: 110–113 days; GL3: 114–116 days; GL4: 117–119 days. The productive indicators of the sows were recorded, as were the survival outcomes of the neonatal pigs. Fetal cardiac frequency and both intensity and frequency of myometrial contractions were monitored using a Corometrics Fetal monitor. The blood gases, electrolytes and glucose levels of the neonates were obtained by means of an automatic blood gas and electrolyte analyser. The GL groups GL1 and GL2 had more prolonged births (&gt;226.26 ± 4.95 min) regardless of litter size (P &lt; 0.05). Of the four groups, GL1 presented the longest duration (P &lt; 0.05) of the expulsion phase (P &lt; 0.05), the highest number of uterine contractions (P &lt; 0.05), and the highest and lowest number of intra-partum deaths (P &lt; 0.05) and live births, respectively. The live birth piglets in this group had both the lowest birthweights (P &lt; 0.05) and the highest incidences of hypercapnia, hyperlactatemia and hypercalcaemia (P &lt; 0.05), which later resulted in lower rates of daily weight gain (P &lt; 0.05). In conclusion, premature births increase the number of intra-partum deaths and result in lower birthweights, the presence of apnoea, and severe metabolic alterations in piglets.

Participation of BKCa2+ and KATP potassium ion channels in the contractility of human term pregnant myometrium in in vitro conditions

The aim of this study was to assess the participation of ligand-sensitive potassium large conductance calcium-activated ion channels (BK(Ca2+) ) and adenosine triphosphate (ATP)-sensitive potassium ion channels (K(ATP) ) using its openers (NS1619 and pinacidil) in the contractility of human term pregnant myometrium in in vitro conditions. Human myometrium tissue samples were collected from term pregnant laboring women who had to undergo cesarean section. The contractility of myometrium was induced by the application of oxytocin into the organ bath. Myometrial strips were incubated with the opener of BK(Ca2+) potassium ion channels NS1619 and its antagonist tetraethylammonium or with the opener of K(ATP) potassium ion channels pinacidil and its antagonist glibenclamide. K(ATP) potassium ion channel's opener pinacidil significantly decreased amplitude of myometrial contractions (P < 0.05) as well as frequency of myometrial contractions (P < 0.05) provoked by oxytocin in human term pregnant myometrium in in vitro conditions. The inhibition of the human myometrial contractions of pinacidil was significantly antagonized by its specific antagonist glibenclamide (P < 0.05). BK(Ca2+) potassium ion channel's opener NS1619 did not significantly affect the contractile activity of human term pregnant myometrium induced by the application of oxytocin in in vitro conditions. In our experimental study we found that the participation of BK(Ca2+) and K(ATP) potassium ion channels in the contractility of human term pregnant myometrium in labor is probably different.

Clostridium botulinum Toxin A Inhibits Contractility in Pregnant Human Myometrium In Vitro

Studies were undertaken to evaluate the effect of Botulinum neurotoxin type-A (BoNTA) preparation on oxytocin-induced contractions of pregnant human myometrium in vitro. Human myometrial tissue was exposed to increasing concentrations (1-50 000 U/mL) of BoNT/A. Isometric contractions were measured using a force displacement transducer. The cumulative effect of BoNT/A on myometrial activity (time to half relaxation [TTR50], frequency, and amplitude) was evaluated. The frequency of myometrial contractions was depressed by 40% from baseline (P < .05) and relaxation time was increased by 30% (P < .05) from baseline within a narrow range of concentrations. There was no significant difference in amplitude. The observed effects were rapidly reversed after complete wash out of the tissue. BoNT/A or its analogues with more specific tissue affinity may be of value as future agents for prevention of unwanted uterine contractile activity associated with preterm labor and fetal surgery.

Interactive effect of sevoflurane with isradipine or indomethacin on spontaneous contractile activity of isolated pregnant rat myometrium

Volatile anesthetics, calcium antagonists and non-steroidal anti-inflammatory drugs inhibit contractile activity of myometrial smooth muscle. The aim of this study was to investigate the interactive effect of sevoflurane with isradipine or indomethacin on spontaneous contractile activity of myometrial strips isolated from pregnant rats. The myometrial strips were excised from rats (250-300 g) at 19-21 days of gestation and mounted in tissue baths for recording of isometric tension. Sevoflurane (0.5 to 3 MAC) inhibited the amplitude and frequency of spontaneous myometrial contractions in a concentration-dependent manner (P<0.05). Sevoflurane responses were repeated in the presence of isradipine (a dihydropyridine-type calcium channel blocker) and indomethacin (a non-selective cyclooxygenase (COX) inhibitor). Pretreatment with isradipine (10(-6) M) or indomethacin (10(-7) M), concentrations that themselves had no effect on spontaneous contractility, significantly increased the inhibitor responses to sevoflurane on amplitude and frequency of myometrial contractions, beginning at 1 MAC (P<0.05). Blockade of calcium channels in myometrial smooth muscle may increase the inhibitor effect of sevoflurane. Further work is needed to determine the cellular mechanism(s) of this interaction.

Clostridium botulinum toxin inhibits myometrial activity in vitro: Possible application on the prevention of preterm labor after fetal surgery

Background/Purpose: The current study aimed to analyze the effects of Clostridium botulinum toxin (Botox) on pregnant myometrium activity in vitro. Methods: Strips of myometrium were obtained from pregnant Wistar rats on gestational day 13 through 15 and placed under controlled conditions within tissue baths containing DeJalon solution. Muscular activity, including amplitude and frequency of contractions, was recorded by a force transducer connected to a polygraph. After stable baseline values were recorded, different concentrations of Botox were added to the tissue baths. Myometrial activity data points for each drug concentration were entered as mean percentual variations of the baseline. A total of 26 uterine samples from 13 animals were studied. Statistical analysis was by single-factor analysis of variance (ANOVA) with P <.05 considered significant. Results: Except for a narrow concentration range, when the effects were nonmonotonic, both amplitude and frequency of myometrial contractions were significantly depressed (P <.05) and eventually totally abolished at most concentrations studied, albeit in a potentially biphasic pattern. Those effects could be reversed by a complete washout of the tissue bath. Conclusions: Within appropriate concentrations, Botox consistently inhibits or completely arrests myometrial activity in potentially reversible fashion. This agent may prove valuable in premature labor prevention after fetal surgery. J Pediatr Surg 38:511-513. Copyright 2003, Elsevier Science (USA). All rights reserved.

Chloride channel blockers 5-nitro-2-(3-phenylpropylamino) benzoic acid and anthracene-9-carboxylic acid inhibit contractions of pregnant rat myometrium in vitro.

We compared in vitro relaxant effect of chloride channel modulators, such as 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) and anthracene-9-carboxylate (9-AC), and beta(2)-adrenergic agonists, such as ritodrine, in pregnant rat myometrium. Isolated myometrial strips were obtained from eight pregnant rats, and the strips were mounted in organ baths for recording isometric tension. The effects of 10(-8)-10(-4) M ritodrine, 10(-6)-3 x 10(-4) M NPPB, and 10(-6)-10(-3) M 9-AC on spontaneous contractions were recorded. Ritodrine (10(-8)-10(-5) M) completely inhibited the amplitude and frequency of spontaneous contractions in myometrial strips isolated from pregnant rats in a concentration-dependent manner, but the relaxant effect of ritodrine at 10(-4) M concentration resulted in tachyphylaxis. The chloride channel blocker NPPB (10(-6)-3 x 10(-4) M) and the chloride transport inhibitor 9-AC (10(-5)-10(-3) M) decreased the amplitude of spontaneous myometrial contractions in a concentration-dependent manner; the maximum inhibition produced by the highest tested concentration of each drug was 43.8% and 42.1% of the original degree of spontaneous contractions, respectively. The frequency of myometrial contractions was significantly inhibited by NPPB and 9-AC beginning with the concentration of 10(-4) M. NPPB and 9-AC appear to be effective relaxants of pregnant rat myometrium. These effects of NPPB and 9-AC might be therapeutically advantageous in clinical management of preterm labor.

Antitachyphylactic Effects of Progesterone and Oxytocin on Term Human Myometrial Contractile Activity In Vitro

To determine whether progesterone causes any changes in the action of oxytocin on the contractile activity of term human myometrium in vitro. Myometrial biopsies from 13 term pregnant women undergoing cesarean delivery were immediately immersed in Hepes buffer or buffer containing 5 micrograms/mL progesterone. In the laboratory under a stereomicroscope, the specimens were dissected into 1 x 7.5-mm muscle strips. These were mounted into six tissue baths and superfused with Hepes buffer and buffer containing 5 micrograms/mL progesterone, 5 micrograms/mL progesterone plus 10 microU/mL oxytocin, 5 micrograms/mL progesterone plus 100 microU/mL oxytocin, 10 microU/mL oxytocin, and 100 microU/mL oxytocin. Isometric tension was recorded constantly for at least 3 hours. The frequency of myometrial contractions and tonus increased by superfusion with progesterone, progesterone plus oxytocin, and oxytocin alone compared to buffer. In addition, a gradual decrease in frequency was observed after 60 minutes of contractions with oxytocin alone, whereas progesterone plus oxytocin had no such decrease. The activity area of contractions was greater with 10 microU/mL oxytocin and decreased with progesterone, progesterone plus both concentrations of oxytocin, and 100 microU/mL oxytocin alone, compared to buffer. Progesterone stimulated the frequency of contractions and tonus of strips from the lower uterine segment of term human myometrium. A lasting increase in the frequency of contractions was observed with superfusion of progesterone plus oxytocin, suggesting that progesterone counteracted the reaction of tachyphylaxis to oxytocin.

Effect of food withdrawal on arterial blood glucose and plasma 13,14-dihydro-15-keto-prostaglandin F 2α concentrations and nocturnal myometrial electromyographic activity in the pregnant rhesus monkey in the last third of gestation: A model for preterm labor?

Pregnant rhesus monkeys were studied between 109 and 149 days of gestation. Food withdrawal for 48 hours (with free access to water) was accompanied by a decrease in maternal whole blood glucose concentration and an increased maternal arterial plasma 13,14-dihydro-15-keto-prostaglandin F2 alpha concentration. On successive nights of the 48-hour period of food withdrawal, there was an increase in the frequency of myometrial contractions as recorded by uterine electromyogram. In the period after food was returned, blood glucose, arterial 13,14-dihydro-15-keto-prostaglandin F2 alpha concentration, and contraction frequency returned to baseline. Because food withdrawal results in the appearance of the nocturnal contraction pattern seen at term, we suggest that this experimental paradigm may be used as a model for preterm labor.