Métodos de indução do trabalho de parto / Methods of induction of labour

Os métodos de indução do parto podem ser divididos em estímulos naturais, estímulos exógenos diretos ou mecânicos e estímulos exógenos indiretos ou farmacológicos, cada qual apresenta suas particularidades nas indicações e contraindicações. O objetivo deste artigo foi realizar uma revisão da literatura consultando Medline/Pubmed e a Biblioteca Cochrane para avaliar a eficácia e segurança na utilização dos principais métodos de indução do trabalho de parto. Apurou-se não haver método ideal de indução do trabalho de parto. Os estímulos naturais e os métodos alternativos carecem de maiores estudos para incentivo de seu uso rotineiro. As prostaglandinas, em destaque o misoprostol, está indicada no Índice de Bishop desfavorável e a ocitocina em condições cervicais favoráveis. Os avanços no campo da biologia molecular tem corroborado que o método ideal deve atuar em sincronismo com a contratilidade uterina e a maturação cervical.(AU)

Methods of labor induction can be classified as natural stimuli, direct exogenous stimuli or mechanical and indirect exogenous stimuli or pharmacological. Which one has its peculiarities in relation to indications and contraindications. The objective of this article was to assess the efficacy and safety of the main methods of induction of labor trough the analysis of the medical literature in Medline/Pubmed and the Cochrane Library to. No ideal method of inducing labor was found. Further studies are required to encourage natural stimuli and alternative methods more often. According to Bishop scores, prostaglandins, (especially misoprostol) are unfavorable and oxytocin in case of favorable cervical environment. Advances in the field of molecular biology have confirmed that the ideal method should work simultaneously with uterine contraction and cervical ripening.(AU)

Oxytocic effects of the aqueous leaf extract of costuslucanusianus - family costaceae on isolated non-pregnant rat uterus

Costus lucanusianus J. Braun [Costaceae] is a climbing herb, found mainly in the Niger Delta region of Nigeria. This plant is locally used in situations of pains, inflammation, dysmenorrhoea and in pyrexia. The purpose of this study was to investigate this claim with view to validating scientifically the ethno-medicinal usage. The aqueous extract was subjected to pharmacological testing in vitro on a piece of isolated rat uterus previously pretreated with 1 mg/kg stilbestrol for 24 h. The dose response curves of oxytocin and that of the extract were first obtained. The effects of antagonists like atropine [1 mg] and salbutamol [2 micro g] on the dose response curve of the extract were also investigated. Possible synergy was investigated via co-administration of the extract and oxytocin. Finally the proximate analysis of the extract was investigated. The aqueous extract of C. lucanusianus and oxytocin both produced a dose dependent contraction of the uterus. An effect of 0.63 +/- 0.06 g force of uterine contraction produced by 12.5 mg of the extract was increased to 1.37 +/- 0.09 g when 200 mg of the extract was administered. Oxytocin at 0.16 i.u was observed to produce a similar force of contraction with 200 mg of the aqueous extract. Synergy was established as co administration of the extract at 200 mg and oxytocin at 0.08 i.u, produced higher contractile effect, significantly higher [p<0.05] than when either the extract [200mg] or oxytocin [0.08 i.u] was administered alone. Both atropine and salbutamol significantly [p<0.0001] inhibited the contractile effect produced by the extract. The inhibitory effect showed by atropine on the contractile effect of the extract seems to suggest the involvement of muscarinic receptors. The proximate analysis carried out in this study is used to establish the identity of the crude drug sample. A moisture content of 10.047% was obtained. The total ash is a measure of the non-volatile inorganic constituents remaining after ashing. The values of 3.42% were obtained

Preterm labour; comparison of efficacy of glyceryl trinitrate patch with salbutamol for prolonging gestation for more than 48 hours, 7 days and upto 37 weeks of gestation

To compare the efficacy of Glyecryl trinitrate patch for prolonging gestation for more than 48 hours, 7 days or up to 37 weeks of gestation with Salbutamol in preterm labour. Compartive descriptive study. Fatima Memorial Hospital Lahore. Dec 2003 to Jan 2005. The study was carried out on 60 pregnant patients admitted in hospital with the symptoms and signs of preterm labour. The results were statistically analyzed using SPSS version 8.0. Two groups [Transdermal Glyceryl Trinitrate group and Salbutamol] comprising 30 patients each were made. In Glyceryl Trinitrate group, transdermal patch was applied and in Salbutamol group, Intravenous infusion titrated according to frequency, duration and intensity of uterine contractions. All the patients in each group were evaluated for prolongation of gestation for 48 hours till 37th week of gestation. The mean prolongation of pregnancy was 26 days in GTN group and 32 days in Salbutamol group. The decrease in frequency of uterine contractions by 67.51 +/- 7.74% in first 48 hours of applying transdermal Glyceryl Trinitrate patch and by 80.14 +/- 8.43% in Salbutamol group which was statistically significant. Trinitrate appears to be a safe, well tolerated and non-invasive but less effectives method of suppressing uterine contraction in preterm labour as compared to Salbutamol

Effect of changes in nitric level oxide on myometrial contractility in pregnant and non-pregnant rats

Nitric oxide [NO] has been recognized as a molecule that shares in regulation of the reproductive system physiology. The present study aimed to investigate the effects of NO excess and NO deficiency on spontaneous myometrial contractions and on myometrial responsiveness to oxytocin as well, in both non-pregnant and late pregnant rats. Female adult rats were divided into two main groups: estrogen-primed non-pregnant model and time-mated late pregnant model. Rats in each model were divided into three groups: a control group, L-arginine-treated group and L-NAME-treated group. Myometrial strips taken from the different groups were suspended in organ bath containing Krebs' solution, gassed with 95% O2 and 5% CO2 for recording of isometric contractions. Spontaneous uterine motility was recorded, followed by oxytocin addition for recording of myometrial responsiveness to this hormone. Serum nitrate level was determined in all rats. L-arginine supplementation caused a significant increase in serum nitrate levels in both rat models, accompanied by decreased spontaneous myometrial contractility and attenuation of the stimulatory effect of oxytocin in both non-pregnant and pregnant rats, compared to the control values. The predominating effect in the non-pregnant model was on the average force, and in the pregnant model on the frequency of contraction. Following treatment with L-NAME. serum nitrate was significantly decreased, yet the spontaneous myometrial contractility and its responsiveness to oxytocin were non-significantly changed in both non-pregnant and pregnant rats, compared to the control group. The NO donor L-arginine has proved to have an inhibitory effect on both spontaneous and oxytocin-induced myometrial contractions, when administered in vivo, in both non-pregnant and late pregnant states, establishing the importance of the L-arginine/NO system as a uterine smooth muscle relaxant. L-arginine could, therefore, provide a useful therapeutic measure for conditions with pathological uterine contractility, like dysmenorrhea or preterm labor, taking into consideration that increased NO attenuates myometrial responsiveness to oxytocin

Antispasmodic effects of Pycnocycla spinosa seed and aerial part extracts on rat ileum and uterus smooth muscle contractions

Hydroalcoholic extract of Pycnocycla spinosa has a relaxant effect on ileum and inhibits castor oil induced diarrhoea in mice. However, effects of P. spinosa seed extracts on ileum and uterus hasn't been investigated. The aim of this study was to investigate effect of P. spinosa seed and extracts of the aerial part on rat ileum and uterus smooth muscle contraction. A 70% ethanol extract of seed and aerial parts of P. spinosa was prepared by a percolation method. Uterine horns or ileum were dissected from non-pregnant female Wistar rats [200-230g] and cut into longitudinal strips and mounted for isotonic recording under Ig tension in Tyrode's solution. Effects of the extracts were examined on tonic contractions induced by KC1 [80mM] on both tissues and on phasic spasm induced by oxytocin [0.002iu/ml] on the uterus. The aerial part extract inhibited rat ileum contractions induced by 80mM KC1 [IC[50] = 42 +/- 3.4 micro g/ml] in a concentration dependent manner and it also inhibited rat uterus contraction induced by 80 mM KC1. However, its inhibitory effects were observed with higher concentration of the extract [IC5o = 420+90 micro g/ml] and at concentration of 1.28mg/ml of the extract in the bath the response was 19+7%. The aerial part extract [40-640 micro g/ml] also reduced the evoked phasic response of uterus by oxytocin [IC[50] = 71 +/- 17.3 micro g/ml]. The seed extract reduced the uterus response to oxytocin in a concentration-dependent manner, and inhibited tissue response completely at 160 micro g/ml [IC[50] = 27 +/- 4 micro g/ml]. From this study it was concluded that the seed extract of P. spinosa have similar inhibitory properties on rat isolated uterus and ileum contractions, while the extract of the aerial part of P. spinosa is more selective inhibitor of ileum contraction, and at higher concentrations it also inhibits uterus spasm

uterine relaxant effect of curcumin in rats ; An in vitro study

Addition of curcumin in concentrations of 1.4 x 10-5 M, 2.8 x 10-5 M and 5.6 x 10-5 M to the organ bath, resulted in significant inhibitions in the normal uterine contractions of non-pregnant rats in the diestrus stage. The recorded decline in the frequency of uterine contractions were 32%, 47% and 67%, while the inhibitions were 50%, 67% and 76% for the amplitude respectively. The reductions in area under the curve [AUC] of contractions were 67%, 71% and 86% for the added concentrations. Pretreatment with curcumin revealed inhibitory effects on the uterine response to oxytocin [10-11M] amounting to 77%, 78% and 72% in AUC with respect to that obtained post-addition of oxytocin alone. These results indicate that the tocolytic potential of curcumin may involve oxytocin receptor-dependent pathway

Comparative study of misoprostol vs dinoprostone for induction of labour.

Various methods of induction of labour may be associated with risk and complications. Therefore, this study has been undertaken to compare the safety and efficacy of intra-vaginal misoprostol (PGE1 analogue) with intra-cervical dinoprostone (PGE2) in progress and induction of labour, the maternal side effects and the foetal outcome. 40 pregnant women aged between 16-35 years with indication of induction of labour participated in the study. Twenty patients (control) were administered 0.5 mg dinoprostone intra-cervically, 12 hourly while 20 patients (study group) were given misoprostol 100 microg, 4 hourly, intravaginally. The mean induction of labour initiation interval was 2.08 +/- 1.46 hours in study group and 2.21 +/- 1.20 hours in dinoprostone group. The Induction delivery interval was 6.92 +/- 4.01 hours in misoprostol group and 12.54 +/- 7.73 in dinoprostone group, whereas vaginal route of delivery was 95% in misoprostol group and 85% in dinoprostone group. Average dosages required were 1.55 +/- 1.02 in misoprostol group and 1.30 +/- 0.46 in dinoprostone group. All these result were statistically significant. Very few maternal side effects were reported in study group. There was no significant difference in foetal out come in either group. Therefore, it can be concluded that misoprostol is easy to administer and is cheap, effective, safe and convenient drug for induction of labour.

Influence of time at which oxytocin is administered during labor on uterine activity and perinatal death in pigs

Oxytocin is extensively used to induce or augment uterine contractions, especially to facilitate the third stage of labor in humans. Administration of oxytocin to parturient sows reduces duration of labor whereas mortality of the offspring may remain unchanged. This study aimed to evaluate whether time of administration of oxytocin during parturition may alter the uterine response and fetal outcomes. Two hundred parturient sows were randomly assigned to intramuscularly receive either saline solution (control group) or oxytocin 0.083 IU/kg immediately after the delivery of the 1st, 4th or 8th piglet (groups O-1, 0-4 and 0-8, respectively). Uterine effects and fetal outcomes were registered in all groups. The duration of labor was 20-40 min shorter (P < 0.0001) and time interval between babies was reduced by 3-5 min (P < 0.0001) in the three groups receiving oxytocin. The duration and intensity of contractions, meconium-stained piglets and intrapartum deaths decreased as time at which oxytocin administered during labor was increased. In group 0-8, we observed approximately 70 percent less meconium-stained piglets and intrapartum deaths than in the control group. In conclusion, oxytocin administered at early phases of parturition to sows may increase duration and intensity of uterine contractions as well as adverse fetal outcomes.

Ion channels: new targets for the next generation of tocolytics agents.

Ion channels are interesting molecules since they mediate not only uterine contraction but also uterine relaxation. We have examined the expression, function, and correlation between the large conductance calcium-activated potassium (BKCa) channel, beta2 adrenoceptor (AR), and long-lasting (L) type calcium (Ca2+) channel. These are the main channels and receptor that are involved in the uterine contraction/ relaxation process. Our evidence has shown that BKCa channel is closely correlated with beta2 AR in mediating uterine relaxation. Both proteins are situated in close proximity on the plasma membrane of human myometrium and are downregulated approximately 50% after the onset of labor. Interestingly, L type Ca2+ channel, which involves in the contraction pathway, seems to be in the same compartmentation as BKCa channel/ beta2 AR macromolecular complex. Further studies are now being conducted to identify the signaling complex components that could potentially be a target for new tocolytic agents.

Hypothyroid state reduces calcium channel function in 18-day pregnant rat uterus.

Hypothyroidism significantly reduced the mean amplitude and increased the mean frequency of spontaneous rhythmic contractions in 18 day pregnant rat uterus. Nifedipine (10(-12)-10(-9) M) and diltiazem (10(-10)-10(-6) M) caused concentration related inhibition of the myogenic responses of the uterine strips obtained from both pregnant and hypothyroid state. However, nifedipine was less potent (IC50:2.11 x 10(-11) M) in pregnant hypothyroid state as compared to pregnant control (IC50: 3.1 x 10(-12) M). Similarly, diltiazem was less potent (IC50: 3.72 x 10(-9) M) in inhibiting the uterine spontaneous contractions in hypothyroid than in pregnant rat uterus (IC50:5.37 x 10(-10) M). A similar decrease in the sensitivity to nifedipine and diltiazem for reversal of K+ (100 mM)-induced tonic contraction and K(+)-stimulated 45Ca2+ influx was observed with these calcium channel antagonists in uterus obtained from hypothyroid pregnant rats compared to the controls. Nifedipine-sensitive influx of 45Ca(2+)-stimulated either by K+ (100 mM) or by Bay K8644 (1,4-dihydro-2,6-methyl-5-nitro-4-[2'-(trifluromethyl)phenyl]-3-pyridine carboxylic acid methyl ester) (10(-9) M) was significantly less in uterine strips from hypothyroid rats compared to controls. The results suggest that the inhibition of uterine rhythmic contractions may be attributable to a reduction in rat myometrial Ca2+ channel function in the hypothyroid state.

Effects of calcium channel blocker, mibefradil, and potassium channel opener, pinacidil, on the contractile response of mid-pregnant goat myometrium.

The present study was undertaken to investigate the in vitro influence of mibefradil, a calcium channel blocker, and pinacidil, a potassium channel opener, on pregnant goat myometrial spontaneous rhythmic contractility and contractions induced with the agonist, oxytocin. Longitudinal strips from the distal region of uterus, collected from goats at midgestation, were mounted in an organ bath for recording isometric contractions. Mibefradil (10(-8)-10(-4) M) or pinacidil (10(-10)-10(-4) M), added cumulatively to the bath at an increment of 1 log unit, caused concentration-dependent inhibition of the spontaneous rhythmic contractions of isolated uterine strips. The rhythmic contraction was, respectively, abolished at 100 and 10 microM concentrations of mibefradil and pinacidil. In a concentration-dependent manner, mibefradil (1 and 10 microM) antagonized the contractions elicited with oxytocin (10(-5)-10(-2) IU). Pretreatment of uterine strips with glibenclamide (10 microM), a selective KATP channel blocker, caused a rightward shift of the concentration-response curve of pinacidil with a concomitant decrease in its pD2 value. Pinacidil (0.3, 1 and 3 microM), in a concentration-related manner, antagonized the oxytocin (10(-5)-10(-2) IU)-induced contractile response. The inhibition of spontaneous rhythmic contractions and antagonism of oxytocin-induced contraction by mibefradil in the pregnant goat myometrium may be related to the antagonism of voltage-dependent Ca2+ channels, while by pinacidil suggests that KATP channel could be a therapeutic target for tocolysis.

Effect of Anthum graveolens fruit extract on rat uterus contractions

Dill [Anethum graveolens] from Umbelliferae is used traditionally to treat convulsions and increasing milk production. Also, in Darab [Fars Province] and Yazd dill fruit is used traditionally to prevent abortion. Its antimicrobial, antihyperlipidaemic, anti-hypercholesteroaemic effects and reducing gastric acid secretion have been reported. The aim of the present study was to investigate the effects of dill fruit hydroalcoholic [DFHE] extract on virgin rat uterus contractions induced by KCI [60mM] and oxytocin [10 mU/ml]. Macerated method was used for extract preparation. Virgin Sprague Dawley female rats were pretreated with an injection of estradiol valerate [5mg/kg, s.c.] 24 hours prior to experiment. Rats were killed and uteri were dissected and mounted in an isolated organ bath containing De Jalon solutions [29°C] bubbled by oxygen. Contractile responses were recorded isometrically under 1g initial tension. The DFHE [0.5, 1, 2, 4 and 8 mg/ml] relaxed both KC1- and oxytocin-induced contractions dosedependently [p<0.0001]. However, the spasmolytic effect of extract on oxytocin-induced contractions was more potent. In Ca[2+] -free, rich K+ [120mM] De Jalon solution, cumulative adding of calcium [0.15, 0.3, 0.6, 1.2 and 2.4 mM], increased contractions dose dependently [p<0.0001]. DFHE [4 mg/ml] shifted this dose-response curve to the right [p<0.05]. In Ca[2+] free solution, oxytocin induced strong contractions if calcium [0.3 mM] was added to the bath. However, DFHE [8 mg/ml] reduced calcium-induced contraction [p<0.001]. The spasmolytic effect of DFHE was reversible. The spasmolytic effect of DFHE [4 mg/ml] was affected neither by propranolol [1micro M] nor by L-NAME [100 micro M]. These results suggest that the relaxatory effect of DFHE on KCI and oxytocin-induced uterus contractions is due, at least in part, to blockade voltage dependent calcium channels and partly by disturbing in releasing calcium from intracellular pool indirectly. In addition, the beta-adrenoceptors and NO are not involved in this inhibitory effect of DFHE. Our results may also support the traditionally usage of dill fruit for preventing abortion

Evaluation of tocolytic efficacy of selective beta2 adrenoceptor agonists on buffalo uterus.

Present study was conducted on prostaglandin F2alpha (PGF2alpha), oxytocin, (OT), potassium chloride (KCI) and barium chloride (BaCl2) pre-contracted perimetrial uterine strips of dioestrus and pregnant buffaloes to evaluate the tocolytic efficacy of selective beta2 adrenoceptor agonists-albuterol (salbutamol) and terbutaline. Cumulative concentration-response curves of both the beta2 adrenoceptor agonists were constructed and the mean effective concentration (EC50) values determined and compared statistically. Based on the comparative EC50 values in relaxing the pre-contracted uterine strips with different spasmogens, the rank order potency of albuterol was found to be--PGF2alpha > BaCl2 > OT > KCl on uterine strips from dioestrus animals, while OT> BaCl2> PGF2alpha >KCl on the uterine strips of pregnant buffaloes. The rank order potency of terbutaline on uterine strips from dioestrus stage animals was- BaCl2 > OT > KCl > PGF2alpha, while BaCl2 > PGF2alpha > KCl > OT on uterine tissues of pregnant animals. Thus, irrespective of the state of uterus, whether gravid or non-gravid, KCl-depolarized uterine tissues required comparatively higher concentrations of albuterol or terbutaline to produce tocolytic effect. High concentrations of K+ in biophase may have interfered with the beta2 adrenoceptor agonists-induced outward K+ current and hyperpolarization. From the results of present study, it was evident that selective beta2 adrenergic agonists had good tocolytic efficacy on the uterus of buffaloes. Further, indirectly the possibility of existence and activation of K(Ca) channels by selective beta2 adrenoceptor agonists in mediating tocolysis of buffalo myometrium can not be ruled out, however, detailed studies using specific K(Ca) channel blockers are required for characterizing the nature of such channels in buffalo uterus.

Tocolytic Effect of Morphine via Increased Metabolic Clearance of Oxytocin in the Baboon

Morphine is known to inhibit nocturnal uterine contractions in several animal models, and oxytocin is known to be a primary causative factor of uterine contractions. The purpose of the present study was to determine the tocolytic effect of morphine in relation to the pharmacokinetics of oxytocin, after a bolus injection of oxytocin. The metabolism of oxytocin was investigated during the third trimester in baboons. Four animals were placed on a tether system with venous and arterial access, including continuous uterine monitoring. Plasma oxytocin levels were determined by radioimmunoassay after extraction with petroleum ether/acetone. Morphine consistently increased the metabolic clearance rate of oxytocin in all four animals (p < 0.05) and this was in accordance with suppressed uterine contractions. We conclude that morphine could be used as an inhibitor of nocturnal uterine contractions, and that this is caused by the morphine induced increased metabolic clearance rate of oxytocin.

Role of Ca2+ on uterine force stimulated by a glycoside from the root of Dalbergia saxatilis.

Uterine muscle contraction is dependent on external Ca2+ and Ca2+ release from cytoplasmic storage sites. In this study, the mechanism of Ca2+ mobilization in uterine muscle cells by glycoside, dalsaxini, isolated from the root of D. Saxatilis was investigated in the rat. Uterine muscle contractility stimulated by dalsaxin was concentration dependent (ED50 0.13 mg/ml) and was significantly attenuated (85%; P < 0.01) in Ca(2+)-free physiological solution and in solutions containing verapamil (0.06-0.48 mumol). The small transient contraction observed in Ca(2+)-free medium was further suppressed by caffeine (2 mmol) and completely abolished in solutions containing Lanthanum chloride [(La3+), 2 mmol]. Contractions stimulated by the glycoside were unaffected by amiloride (50-83 mumol) in Ca(2+)-free and Ca(2+)-containing media. Dalsaxin also altered the pattern of uterine contraction stimulated by high potassium depolarization from fast-phasic to a sustained but transient plateau. It is concluded that dalsaxin causes uterine muscle contraction by mobilizing external Ca2+ through predominantly a voltage-dependent Ca2+ channel.

Adrenergic influence of uterine muscle contractions stimulated by a glycoside from the root of Dalbergia saxatilis.

The mechanism of uterine muscle contraction stimulated by a triterpenoid glycoside (dalsaxin) isolated from the root of D. saxatilis was investigated by in vitro methods in the rat. Dalsaxin caused a dose-related increase in uterine muscle contraction. The contraction was single and transient and was abolished by moderate doses of isoprenaline (1.80 nmol-0.40 mumol) and salbutamol (0.13-25 mumol). Adrenaline (9.10 nmol) also caused a reversible decrease (92.6%; P < 0.01) in myometrial contraction stimulated by this glycoside (0.24 mg/ml). Uterine muscle responses to dalsaxin (0.24 mg/ml) were enhanced by the beta-adrenergic receptor antagonist, propranolol, in a dose related manner. Atipamezole (1.50 ng/ml) but not prazosin (7.72 nmol-15.60 nmol) substantially reduced (80%; P < 0.01) myometrial contractions induced by this uterine spasmogen. The results suggest that dalsaxin enhances uterine muscle contraction by stimulating post junctional alpha 2-adrenergic receptors, presumably by inhibiting plasma membrane adenylate cyclase system and its associated increase in intracellular cAMP content.

Involvement of K+ channels in the relaxant responses to various agonists in estrogen primed rat uterus.

The present investigation was undertaken to study the effects of K+ channel openers in the relaxant responses to various agonists in estrogen primed rat uterus. Adrenaline and isoprenaline produced a dose-dependent relaxation in the estrogen primed rat uterus. The relaxant responses were found to be significantly potentiated when the preparations were exposed to PSS devoid of calcium. The responses to isoprenaline were found to be greater in the preparations depolarized with 40 mM KCl instead of 80 mM KCl. KCl failed to produce any contractile effect in the presence of D-600. Further, the addition of D-600 completely relaxed the KCl depolarized rat uterus. Pinacidil and cromakalim failed to relax 80 mM KCl depolarized rat uterus. However, they produced dose-dependent relaxation in the preparations depolarized with 40 mM KCl. The relaxant responses to pinacidil and cromakalim were competitively blocked by procaine. However, they were not altered by either propranolol or cimetidine. The relaxant responses to isoprenaline and histamine were found to be potentiated by pinacidil and cromakalim. These results indicate that in rat uterus in addition to adenylate cyclase c-AMP, potassium channels are also involved in the relaxant responses to isoprenaline and histamine.

effect of thiola, piroxicam and diltiazem on the uterine contratility of gamma-irraidated rats

Accidental radfiation exposure raises concern for functional modifications in the uterine physiology. In the current work, total body gamma-irradiation [0.7, 1.4 and 2.1 Gy] of non-pregnant adult female albino rats increased significantly the frequency and amplitude of uterine contractions in-vivo. Administration of Thiola [a sulghydryl containing agent] in doses of 100 or 250 mg/kg, pre-irradiation, or Piroxicam [a potent prostaglandin inhibitor] in a dose of 2 mg/kg, pre- or post-irradiation failed to normalize the changes induced by gamma-irradiation. However, administration of Diltiazem [a Ca+2 channel blocker, 8 mg/kg] pre- or post-irradiation caused significant decrease in the frequency of uterine contractions [21% and 24% respectively] as well as the amplitude of contractions [62% and 39 respectively] in comparison to the uterotonic pattern of gamma-irradiation alone. The results indicate a promising tocolytic activity of Diltiazem against the uterotonic effect of gamma-radiation

The effect of spironolactone on the rat uterus.

Our experimental study showed that in a dose related manner SP has successful inhibitory effect on the rat uterine horn, and also on the smooth muscle organs; ileum and trachea. We guess that SP can be used in well regulated dosed with least side effects to arrest preterm labor on human being in the future. Up to date there is no manuscript about contraction inhibitory effect of SP on the uterus. We hope this study will be of scientific help.