Spontaneous Myometrial Contractions Research Articles

Dual effect of nifedipine on pregnant human myometrium contractility: Implication of TRPC1.

Nifedipine, an L‐type voltage‐gated Ca2+ channel (L‐VGCC) blocker, is one of the most used tocolytics to treat preterm labor. In clinical practice, nifedipine efficiently decreases uterine contractions, but its efficacy is limited over time, and repeated or maintained nifedipine‐based tocolysis appears to be ineffective in preventing preterm birth. We aimed to understand why nifedipine has short‐lasting efficiency for the inhibition of uterine contractions. We used ex vivo term pregnant human myometrial strips treated with cumulative doses of nifedipine. We observed that nifedipine inhibited spontaneous myometrial contractions in tissues with high and regular spontaneous contractions. By contrast, nifedipine appeared to increase contractions in tissues with low and/or irregular spontaneous contractions. To investigate the molecular mechanisms activated by nifedipine in myometrial cells, we used the pregnant human myometrial cell line PHM1‐41 that does not express L‐VGCC. The in vitro measurement of intracellular Ca2+ showed that high doses of nifedipine induced an important intracellular Ca2+ entry in myometrial cells. The inhibition or downregulation of the genes encoding for store‐operated Ca2+ entry channels from the Orai and transient receptor potential‐canonical (TRPC) families in PHM1‐41 cells highlighted the implication of TRPC1 in nifedipine‐induced Ca2+ entry. In addition, the use of 2‐APB in combination with nifedipine on human myometrial strips tends to confirm that the pro‐contractile effect induced by nifedipine on myometrial tissues may involve the activation of TRPC channels.

Anti-inflammatory and utero-relaxant effect of α-bisabolol on the pregnant human uterus.

The aim of this study was to evaluate the in vitro anti-inflammatory and utero-relaxant effect of α-bisabolol on the pregnant human myometrium. Samples from the pregnant human myometrium were used in functional tests to evaluate the inhibitory effect of α-bisabolol (560, 860, 1,200 and 1,860 µM) on spontaneous myometrial contractions. The intracellular cyclic adenosine monophosphate (cAMP) levels generated in response to α-bisabolol in human myometrial homogenates were measured by ELISA. The anti-inflammatory effect of α-bisabolol was determined through the measurement of two pro-inflammatory cytokines, tumor necrosis factor-α (TNFα) and interleukin (IL)-1β, and the anti-inflammatory cytokine IL-10, in pregnant human myometrial explants stimulated with lipopolysaccharide (LPS). Forskolin was used as a positive control to evaluate the cAMP and cytokine levels. α-Bisabolol was found to induce a significant inhibition of spontaneous myometrial contractions at the highest concentration level (p<0.05). α-Bisabolol caused a concentration-dependent decrease in myometrial cAMP levels (p<0.05) and a concentration-dependent decrease in LPS-induced TNFα and IL-1β production, while IL-10 production did not increase significantly (p>0.05). The anti-inflammatory and utero-relaxant effects induced by α-bisabolol were not associated with an increase in cAMP levels in pregnant human myometrial samples. These properties place α-bisabolol as a potentially safe and effective adjuvant agent in cases of preterm birth, an area of pharmacological treatment that requires urgent improvement.

A comparison of the effects of lindane and FeCl3/ADP on spontaneous contractions in isolated rat or human term myometrium

Oxidative stress affects the contractile behavior of smooth muscle resulting in complications during labor. Toxicants such as lindane and ferric chloride (FeCl3)/adenosine diphosphate (ADP) cause oxidative stress and have previously been shown to inhibit smooth muscle contraction. In this study we examined the effects of the oxygen species scavengers, ascorbic acid and N-acetylcysteine on lindane and FeCl3/ADP’s inhibition of spontaneous myometrial contractions in rat and human myometrium. Lindane and FeCl3/ADP gave rise to concentration-dependent reductions in rat (EC50 11.8×10−6M and 0.9×10−3M) and human myometrial contractions (EC50 16.3×10−6M and 1.1×10−3M, respectively). Pre-treatment with N-acetylcysteine significantly increased the EC50 for the effects of lindane on motility index of human tissue and reduced the maximum inhibitory effect of FeCl3/ADP on contractions in both rat and human myometrium. Ascorbic acid reduced the effects of FeCl3/ADP in rat tissue only. In conclusion pre-treatment with specific antioxidants may protect both rat and human myometrium from the inhibitory effects of lindane and FeCl3/ADP.

Effect of reproductive ageing on pregnant mouse uterus and cervix.

Key points Older pregnant women have a greater risk of operative delivery, still birth and post‐term induction.This suggests that maternal age can influence the timing of birth and processes of parturition.We have found that increasing maternal age in C57BL/6J mice is associated with prolongation of gestation and length of labour.Older pregnant mice also had delayed progesterone withdrawal and impaired myometrial function.Uterine ageing and labour dysfunction should be investigated further in older primigravid women. Advanced maternal age (≥35 years) is associated with increased rates of operative delivery, stillbirth and post‐term labour induction. The physiological causes remain uncertain, although impaired myometrial function has been implicated. To investigate the hypothesis that maternal age directly influences successful parturition, we assessed the timing of birth and fetal outcome in pregnant C57BL/6J mice at 3 months (young) and 5 months (intermediate) vs. 8 months (older) of age using infrared video recording. Serum progesterone profiles, myometrium and cervix function, and mitochondrial electron transport chain complex enzymatic activities were also examined. Older pregnant mice had a longer mean gestation and labour duration (P < 0.001), as well as reduced litter size (P < 0.01) vs. 3‐month‐old mice. Older mice did not exhibit the same decline in serum progesterone concentrations as younger mice. Cervical tissues from older mice were more distensible than younger mice (P < 0.05). Oxytocin receptor and connexin‐43 mRNA expression were reduced in the myometrium from 8‐month‐old vs. 3‐month‐old mice (P < 0.05 and P < 0.01 respectively) in tandem with more frequent but shorter duration spontaneous myometrial contractions (P < 0.05) and an attenuated contractile response to oxytocin. Myometrial mitochondrial copy number was reduced in older mice, although there were no age‐induced changes to the enzymatic activities of the mitochondrial electron transport chain complexes. In conclusion, 8‐month‐old mice provide a useful model of reproductive ageing. The present study has identified potential causes of labour dysfunction amenable to investigation in older primigravid women.

The combination tocolytic effect of magnesium sulfate and an oxytocin receptor antagonist in myometrium from singleton and twin pregnancies

Preterm birth at <37 weeks of gestation is the most common and costly complication of pregnancy and remains the leading cause of neonatal morbidity, death, and reduced achievement in surviving infants. Magnesium sulfate is 1 class of tocolytics for threatened preterm labor; however, its clinical efficacy has been questioned. Twin pregnancies are at increased risk of preterm delivery compared with singleton gestations, which suggests that there is twin-specific risk to preterm delivery in twins. The prevention strategies that are applied to singleton pregnancies, however, have not been shown to be effective in twin pregnancies. The purpose of this study was to compare the relaxant effect of magnesium sulfate on spontaneous and oxytocin-augmented contractions of human myometrium from singleton and twin pregnancies and to examine whether the effect of oxytocin on magnesium sulfate's potency could be reversed with the use of the oxytocin receptor antagonist, atosiban. Myometrium was obtained at the time of prelabor cesarean section (36-40 weeks of gestation) from women with singleton (n=23) or twin (n=12) pregnancy. Isometric tension recordings were made on myometrial strips that were mounted in organ baths that were superfused with physiologic saline solution. Strips were exposed to rising concentrations of magnesium sulfate, and the effect on spontaneous contractions or stimulated with oxytocin (0.5 nmol/L) and in the presence or absence of atosiban (100 nmol/L) was recorded. The contractile characteristics after each application of magnesium sulfate, which included amplitude of contraction and activity integral, were measured. Concentration-response curves were fitted with the use of nonlinear regression and comparison of the negative logarithm of the 50% reduction in activity values. Magnesium sulfate exerted an equal concentration-dependent inhibitory effect on spontaneous myometrial contractions from both singleton and twin myometrium (P>.05). The application of oxytocin produced a significant rightward shift in the concentration-response curves (P<.0001), but no differences were found between pregnancy groups (P>.05). The addition of atosiban shifted concentration-response curves significantly back to the left for amplitude of contraction and activity integral in singletons (P<.0001). However, only activity integral was significantly reversed in twins (P<.01). Magnesium sulfate is equipotent in suppressing contractions in singleton and twin myometrium. Oxytocin (0.5 nmol/L) significantly reduces the tocolytic potency of magnesium sulfate, which may explain, in part, magnesium sulfate's poor efficacy invivo; however, this can be reversed partially by the use of an oxytocin receptor antagonist. Combination tocolysis that involves oxytocin receptor antagonists requires further investigation.

Regulation of myometrial contraction by ATP-sensitive potassium (KATP) channel via activation of SUR2B and Kir 6.2 in mouse.

ATP-sensitive potassium (KATP) channels are well characterized in cardiac, pancreatic and many other muscle cells. In the present study, functional expression of the KATP channel was examined in non-pregnant murine longitudinal myometrium. Isometric contraction measurements and Western blot were used. KATP channel openers (KCOs), such as pinacidil, cromakalim, diazoxide and nicorandil, inhibited spontaneous myometrial contractions in a reversible and glibenclamide-sensitive manner. KCOs inhibited oxytocin (OXT)- and prostaglandin F2α (PGF2α)-induced phasic contractions in a glibenclamide-sensitive manner. SUR2B and Kir6.2 were detected by Western blot, whereas SUR1, SUR2A and Kir6.1 were not. These results show that pinacidl, cromakalim, diazoxide and nicorandil-sensitive KATP channels exist in murine myometrium, which are composed of SUR2B and Kir6.2. Based on the modulatory effects of the KATP channel on spontaneous contraction, OXT- and PGF2α-induced contractions, KATP channels seem to play an essential role in murine myometrial motility via activation of SUR2B and Kir6.2.

Gebe ratlarda isradipinin uterus kontraksiyonları üzerine inhibitör etkileri

Objective: To investigate the effects of isradipine, which is a calcium channel blocker, on late pregnant rats’ myometrium under in vitro conditions. Methods: Stripes were obtained from the myometriums of pregnant rats which were decapitated on the 18 days of gestation. The effects of isradipine on myometrium were investigated in four groups and four cumulative doses: 1 ng/ml, 10 ng/ml, 0.1 μg/ml, 1 μg/ml. Group 1: spontaneous myometrial contractions, Group II: myometrial contractions induced by oxytocin, Group III: myometrial contractions induced by prostaglandin, Group IV: myometrial contractions induced by oxytocin in calcium-free medium. Wilcoxon signed ranks test was used for the statistical analysis and p<0.05 was considered statistically significant. Results: Group 1: compared to the control group, 10 ng/mL and 0.1 μg/mL isradipine decreased the amplitude of uterine contractions. Group II: 0.1 μg/mL isradipine decreased the frequency of contractions (p=0.02). Isradipine decreased the amplitudes of contractions in the doses of 10 ng/mL and 0.1 μg/mL (p=0.02 for each dose). Group III: 0.1 μg/mL isradipine decreased the frequency of contractions (p=0.02). Isradipine decreased the amplitudes of contractions in the doses of 10 ng/mL and 0.1 μg/mL (p=0.02 for each dose). One μg/mL isradipine completely removed all spontaneous and induced contractions. Group IV: when compared to mediums with calcium, both amplitudes and frequencies of the contractions were found lower in this group (p<0.001). Isradipine was only used in the dose of 1 μg/mL and it completely removed all contractions.

Effect of NS11021, a novel BKCA channel opener, on non-pregnant and pregnant mouse myometrial contractility

BackgroundIt has been hypothesised that down-regulation of the potassium BKCa channel function at term is involved in myometrial activation at labour onset. However, there are conflicting reports on the contribution...

The contribution of Kv7 channels to pregnant mouse and human myometrial contractility

Premature birth accounts for approximately 75% of neonatal mortality and morbidity in the developed world. Despite this, methods for identifying and treating women at risk of preterm labour are limited and many women still present in preterm labour requiring tocolytic therapy to suppress uterine contractility. The aim of this study was to assess the utility of Kv7 channel activators as potential uterine smooth muscle (myometrium) relaxants in tissues from pregnant mice and women. Myometrium was obtained from early and late pregnant mice and from lipopolysaccharide (LPS)-injected mice (day 15 of gestation; model of infection in pregnancy). Human myometrium was obtained at the time of Caesarean section from women at term (38–41 weeks). RT-PCR/qRT-PCR detected KCNQ and KCNE expression in mouse and human myometrium. In mice, there was a global suppression of all KCNQ isoforms, except KCNQ3, in early pregnancy (n= 6, P < 0.001 versus late pregnant); expression subsequently increased in late pregnancy (n= 6). KCNE isoforms were also gestationally regulated (P < 0.05). KCNQ and KCNE isoform expression was slightly down-regulated in myometrium from LPS-treated-mice versus controls (P < 0.05, n= 3–4). XE991 (10 μM, Kv7 inhibitor) significantly increased spontaneous myometrial contractions in vitro in both human and mouse myometrial tissues (P < 0.05) and retigabine/flupirtine (20 μM, Kv7 channel activators) caused profound myometrial relaxation (P < 0.05). In summary, Kv7 activators suppressed myometrial contraction and KCNQ gene expression was sustained throughout gestation, particularly at term. Consequently, activation of the encoded channels represents a novel mechanism for treatment of preterm labour.

Women’s health—what’s new worldwide

Women’s health—what’s new worldwide

Expression and function of Kv7 channels in murine myometrium throughout oestrous cycle

This study represents an extensive characterisation of the expression and functional impact of KCNQ and KCNE accessory subunits in a murine uterus using a combination of quantitative reverse transcription polymerase chain reaction, Western blot analysis, patch clamp electrophysiology and isometric tension recording. The use of uterine tissue throughout the oestrous cycle provided a physiological model with which to assess hormonal regulation of these genes. Messenger ribonucleic acid for all KCNQ genes were detected throughout the oestrous cycle with the KCNQ1 message predominant. KCNE isoforms were detected at each stage of the cycle. KCNE4 was the most abundant (p < 0.0001), and KCNQ1, KCNQ5 and KCNE1 were up-regulated in metestrous (p < 0.0001). The K(v)7 channel inhibitor XE991 reduced outward K(+) currents and significantly increased spontaneous myometrial contractions (p < 0.05), whereas retigabine (K(v)7 activator) significantly relaxed uterine tissues (p < 0.001). These data are the first to characterise KCNQ and KCNE gene expression in a cell type outside of neurons and the cardiovascular system.

THG113.31, a specific PGF2alpha receptor antagonist, induces human myometrial relaxation and BKCa channel activation

BackgroundPGF2alpha exerts a significant contractile effect on myometrium and is central to human labour. THG113.31, a specific non-competitive PGF2alpha receptor (FP) antagonist, exerts an inhibitory effect on myometrial contractility. The BKCa channel is ubiquitously encountered in human uterine tissue and plays a significant role in modulating myometrial cell membrane potential and excitability. The objective of this study was to investigate potential BKCa channel involvement in the response of human myometrium to THG113.31.MethodsSingle and whole-cell electrophysiological BKCa channel recordings from freshly dispersed myocytes, were investigated in the presence and absence of THG113.31. Functional studies investigated the effects of THG113.31 on isolated spontaneous myometrial contractions, in the presence and absence of the BKCa channel blocker, iberiotoxin.ResultsSingle channel recordings identified the BKCa channel as a target of THG113.31. THG113.31 significantly increased the open state probability of these channels [control 0.023+/-0.006; 10 microM THG113.31 0.087+/-0.012 (P = 0.009); and 50 microM THG113.31 0.1356+/-0.018 (P = 0.001)]. In addition, THG113.31 increased whole-cell BKCa currents over a range of membrane potentials, and this effect was reversed by 100 nanoM IbTX. Isometric tension studies demonstrated that THG113.31 exerted a significant concentration-dependent relaxant effect on human myometrial tissue and pre-incubation of strips with IbTX abolished this effect on spontaneously occurring contractions.ConclusionThese data suggests that activation of the BKCa channel may contribute, at least partially, to the uterorelaxant effect of THG113.31.

The role of phospholipase Cγ1 tyrosine phosphorylation during phasic myometrial contractions

Phospholipase Cgamma1 (PLCgamma1) is expressed in myometrium and is activated by tyrosine phosphorylation. These studies sought to determine the association between PLCgamma1 tyrosine phosphorylation and spontaneous uterine contractions. In vitro contraction studies were performed with spontaneously contracting rat uterine strips along with strips that were treated with potassium bisperoxo(1,10 phenanthroline)oxovanadate (bpV(phen), a protein tyrosine phosphatase inhibitor. Additional studies were performed with phenylarsine oxide (a PLCgamma inhibitor) and other inhibitors. Western blots were performed to determine the phosphotyrosine PLCgamma1 levels. Spontaneous contractile activity and tyrosine phosphorylation of PLCgamma1 (but not PLCgamma2) were increased significantly in response to bpV(phen); in contrast, oxytocin and thrombin produced comparable contractile activity but did not alter phosphotyrosine-PLCgamma1. Phenylarsine oxide and neomycin significantly decrease bpV(phen)-stimulated contractions and PLCgamma1 tyrosine phosphorylation; other inhibitors only suppressed contractions. These studies support the hypothesis that spontaneous myometrial contractions are associated with tyrosine phosphorylation of PLCgamma1; both of which are further enhanced by the inhibition of protein tyrosine phosphatase activity.

Magnesium ion inhibits spontaneous and induced contractions of isolated uterine muscle

Aim. Magnesium sulfate, mainly used in obstetrics to treat eclamptic convulsions, is currently questioned as to its clinical tocolytic effect. We aimed to study the relaxant action (if any) of magnesium sulfate on in vitro pregnant and non-pregnant myometrium.Methods. Myometrial strips, harvested from five pregnant women (35–39 gestational weeks) during Cesarean procedures indicated for dystocia or scared uterus and five non-pregnant women during hysterectomy or myomectomy for benign conditions, were placed in a Krebs–Henseleit solution organ bath and the isometric force was registered. We assessed the effect of Mg2+ (magnesium sulfate) at different concentrations (0.50–10 mM) on spontaneous and oxytocin-induced (1 μM) myometrial contractility.Results. Mg2+ temporarily reduced spontaneous myometrial contractions in a dose-dependent manner, with efficient regimens at 2.0–2.5 mM, and arrested contractility completely at 3 mM. Oxytocin-induced contractions were reduced by 30–40% at 8 mM and decreased further at 9–10 mM. Induced contractions were reduced, in a dose-dependent and time-dependent manner (maximum effect at 20 min), at higher Mg2+ concentrations and with non-significant proportional differences between pregnant and non-pregnant myometrium.Conclusions. The present in vitro study suggests a possible benefit of Mg2+ in the inhibition of spontaneous myometrial contractility, but not of uterine-induced hyperactivity.

Anti-inflammatory and relaxatory effects of prostaglandin E2 in myometrial smooth muscle

The onset of human labour is complex and involves multiple mediators, prostaglandins, cytokines and chemokines. However, whilst prostaglandins are routinely used for labour induction and inhibitors of prostaglandin synthesis are used to prevent pre-term labour, these practices are not invariably successful, and the rationale for their use is equivocal. As COX-2 and prostaglandin E(2) (PGE(2)) production is increased towards term, we have investigated the effect of PGE(2) and other cAMP-elevating agents on events associated with labour induction. Time-dependent increases in granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-8 (IL-8) release were observed following treatment of primary human myometrial smooth muscle (HMSM) cells with IL-1beta, via mechanisms that required de novo transcription and translation. Prior treatment with PGE(2) (1 microM) produced 86 and 80% decreases in GM-CSF and IL-8 release, respectively. Similarly, the cAMP analogue, 8-bromo-cAMP (8Br-cAMP) and the phosphodiesterase-4 (PDE(4)) inhibitor, rolipram, also repressed GM-CSF and IL-8 release. In addition, PGE(2), 8Br-cAMP, rolipram and salbutamol all had a dose-dependent inhibitory effect on spontaneous myometrial contractions in vitro. In this study, PGE(2) reduced the release of factors associated with cervical ripening and attenuated force development in myometrial smooth muscle, raising the possibility that in myometrium, PGE(2) may act to down-regulate some of the processes that contribute to the onset of human labour and may be beneficial in helping to maintain pregnancy towards term.

Comparing the relaxing effects of desflurane and sevoflurane on oxytocin-induced contractions of isolated myometrium in both pregnant and nonpregnant rats

In this study, the effects of 2 volatile anesthetics, desflurane and sevoflurane, on oxytocin-induced contractions of isolated myometrium in pregnant and nonpregnant rats were compared. Twenty pregnant and 20 nonpregnant Wistar albino rats were studied at 19 to 20 days' gestation (term, 22 days). A total of 40 myometrial strips were obtained from pregnant and nonpregnant rats, and each of these was randomly assigned to 1 of 4 groups (n=10, each group). After spontaneous myometrial contractions were induced in the De Jalon solution, the effects of 0.5, 1, and 2 minimum alveolar anesthetic concentrations (MAC) of desflurane or sevoflurane, in the absence and presence of oxytocin (2 x 10(-9) M), were investigated. Oxytocin significantly increased the amplitude and duration of spontaneous contractions in longitudinal myometrial strips (P<.05), but not the frequency. Both agents (except for 0.5 MAC in the nonpregnant group) inhibited the duration, amplitude, and frequency of induced contractions in a dose-dependent manner. The inhibitory potencies of desflurane and sevoflurane were similar. It was found that isolated strips of pregnant rat myometrium were more sensitive to the inhibitory effects of both agents than were the nonpregnant rat myometrial strips.

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.

YC-1, a Nitric Oxide-Independent Activator of Soluble Guanylate Cyclase, Inhibits the Spontaneous Contractions of Isolated Pregnant Rat Myometrium

The aim of this study was to investigate the effect of YC-1 (3-(5′-hydroxymethyl-2′-furyl)-1-benzyl indazole) on spontaneous contractions and levels of cyclic GMP (cGMP) of myometrial strips isolated from pregnant rats. It is a nitric oxide-independent soluble guanylate cyclase activator. Myometrial strips were obtained from eight pregnant Wistar albino rats and were mounted in organ baths for the recording of isometric tensions. We evaluated the effect of increasing concentrations of YC-1 on spontaneous myometrial contractions and on contractions of myometrial smooth muscle pretreated with methylene blue (10-5M), tetraethylammonium chloride (TEA) (3 × 10-4M), and glibenclamide (10-6M). YC-1 (10-9–3 × 10-5M) concentration-dependently decreased the amplitude and frequency of spontaneous contractions of myometrial strips. The inhibition of the amplitude and frequency of spontaneous contractions by YC-1 were antagonized with methylene blue (10-5M) and TEA (3 × 10-4M), but they were not changed by glibenclamide (10-6M); however, the antagonistic effect of methylene blue was significantly more than that of TEA (P<0.05). We also evaluated the effect of YC-1 on the levels of cGMP in myometrial strips obtained from pregnant rat uterine horns. YC-1-stimulated myometrial strips showed an excessive elevation in myometrial cGMP that declined slowly during the subsequent washout period. These results show that YC-1 decreases spontaneous contractile activity of myometrial strips isolated from pregnant rat and causes elevation of myometrial cGMP levels in vivo. This effect of YC-1 is significantly reduced by the methylene blue and TEA, suggesting the activation of soluble guanylate cyclase and Ca2+-sensitive K+ channels as the mechanisms of action.

Role of Src family kinases during tyrosine phosphorylation of phospholipase C-γ1 during phasic myometrial contractions

The intracellular signaling events during spontaneous myometrial contractions are yet to be defined. Previous reports have suggested that activation of PLC-γ1 in response to tyrosine phosphorylation plays an important role. These studies sought to characterize the Src kinase(s) involved in PLC-γ1 activation.

The direct depressant effects of desflurane and sevoflurane on spontaneous contractions of isolated gravid rat myometrium

Our purpose was to investigate the direct depressant effects of desflurane and sevoflurane at 0.5, 1 and 2 minimum alveolar concentrations (MAC) on spontaneous contractions of isolated gravid rat myometrium. Ten gravid, albino Wistar rats, weighing 240–310 g and at 19-20 days’ gestation were used. Sixty myometrial strips were obtained from 10 rats, and randomly assigned into six groups of 10. After obtaining spontaneous myometrial contractions in de Jalon solution for 45 min, 0.5, 1 or 2 MAC of desflurane or sevoflurane were continuously bubbled in the bath for 15 min and myometrial contractions evaluated during the last 10 min. Desflurane 0.5 MAC did not affect duration or amplitude of spontaneous contractions, but frequency was significantly decreased ( P<0.05). Duration, amplitude and frequency were all significantly decreased by desflurane 1 and 2 MAC ( P<0.05). Sevoflurane did not affect duration, amplitude or frequency at 0.5 MAC, but amplitude and frequency were significantly decreased at 1 MAC and all were significantly decreased at 2 MAC ( P<0.05). The frequency of contractions was decreased 21.2% with 1 MAC desflurane versus 17.1% with 1 MAC sevoflurane. The amplitude and frequency of contractions were decreased 48.2% and 48.7% with 2 MAC desflurane versus 58.9% and 49.3% with 2 MAC sevoflurane, respectively. We suggest that due to tocolytic activity, desflurane and sevoflurane can be useful in non-obstetric surgery during pregnancy.