Review and Study of Uterine Bioelectrical Waveforms and Vector Analysis to Identify Electrical and Mechanosensitive Transduction Control Mechanisms During Labor in Pregnant Patients.

The bioelectrical signals that produce uterine contractions during parturition are not completely understood. The objectives are as follows: (1) to review the literature and information concerning uterine biopotential waveforms generated by the uterus, known to produce contractions, and evaluate mechanotransduction in pregnant patients using electromyographic (EMG) recording methods and (2) to study a new approach, uterine vector analysis, commonly used for the heart: vectorcardiography analysis. The patients used in this study were as follows: (1) patients at term not in labor (n = 3); (2) patients during the 1st stage of labor at cervical dilations from 2 to 10 cm (n = 30); and (3) patients in the 2nd stage of labor and during delivery (n = 3). We used DC-coupled electrodes and PowerLab hardware (model no. PL2604, ADInstruments, Castle Hill, Australia), with software (LabChart, ADInstruments) for storage and analysis of biopotentials. Uterine and abdominal EMG recordings were made from the surface of each patient using 3 electrode pairs with 1 pair (+ and -, with a 31-cm spacing distance) placed in the right/left position (X position) and with 1 pair placed in an up/down position (Y position, also 31 cm apart) and with the third pair at the front/back (Z position). Using signals from the three X, Y, and Z electrodes, slow (0.03 to 0.1 Hz, high amplitude) and fast wave (0.3 to 1 Hz, low amplitude) biopotentials were recorded. The amplitudes of the slow waves and fast waves were significantly higher during the 2nd stage of labor compared to the 1st stage (respectively, p = 9.54 × e-3 and p = 3.94 × e-7). When 2 channels were used, for example, the X vs. Y, for 2-D vector analysis or 3 channels, X vs. Y vs. Z, for 3-D analysis, are plotted against each other on their axes, this produces a vector electromyometriogram (EMMG) that shows no directionality for fast waves and a downward direction for slow waves. Similarly, during the 2nd stage of labor during abdominal contractions ("pushing"), the slow and fast waves were enlarged. Manual applied pressure was used to evoke bioelectrical activity to examine the mechanosensitivity of the uterus. Conclusions: (1) Phasic contractility of the uterus is a product of slow waves and groups of fast waves (bursts of spikes) to produce myometrial contractile responses. (2) 2-D and 3-D uterine vector analyses (uterine vector electromyometriogram) demonstrate no directionality of small fast waves while the larger slow waves represent the downward direction of biopotentials towards the cervical opening. (3) Myometrial cell action event excitability and subsequent contractility likely amplify slow wave activity input and uterine muscle contractility via mechanotransduction systems. (4) Models illustrate the possible relationships of slow to fast waves and the association of a mechanotransduction system and pacemaker activity as observed for slow waves and pacemakers in gastrointestinal muscle. (5) The interaction of these systems is thought to regulate uterine contractility. (6) This study suggests a potential indicator of delivery time. Such vector approaches might help us predict the progress of gestation and better estimate the timing of delivery, gestational pathologies reflected in bioelectric events, and perhaps the potential for premature delivery drug and mechanical interventions.

Use of Non-invasive Uterine Electromyography in the Diagnosis of Preterm Labour.

Predictive values of methods currently used in the clinics to diagnose preterm labour are low. This leads to missed opportunities to improve neonatal outcomes and, on the other hand, to unnecessary hospitalizations and treatments. In addition, research of new and potentially more effective preterm labour treatments is hindered by the inability to include only patients in true preterm labour into studies. Uterine electromyography (EMG) detects changes in cell excitability and coupling required for labour and has higher predictive values for preterm delivery than currently available methods. This methodology could also provide a better means to evaluate various therapeutic interventions for preterm labour. Our manuscript presents a review of uterine EMG studies examining the potential clinical value that this technology possesses over what is available to physicians currently. We also evaluated the impact that uterine EMG could have on investigation of preterm labour treatments by calculating sample sizes for studies using EMG vs. current methods to enrol women. Besides helping clinicians to make safer and more cost-effective decisions when managing patients with preterm contractions, implementation of uterine EMG for diagnosis of preterm labour would also greatly reduce sample sizes required for studies of treatments.

Actions of progestins for the inhibition of cervical ripening and uterine contractions to prevent preterm birth.

The importance of progesterone (P4) for maintenance of pregnancy, its role in cervical ripening and uterine contractions is at least partly established and therefore, not surprisingly, the basis for the concept to use P4 as a treatment for preterm birth. Due to the complexity of the condition of preterm birth there are still questions concerning the optimal population that might benefit, timing of treatment, dosage, vehicle and route of administration. Recently vaginal P4 and intramuscular 17-alpha-hydroxyprogesterone caproate (17P) have been used to prevent preterm birth in patients with a high risk for early delivery. The aim of this study was to assess cervical changes throughout pregnancy in rats and the timing of term and preterm delivery after various progestin treatments given by different routes and vehicles in hope of identifying better treatment regimens. This paper presents results that suggest that there are better routes of treatment than the vaginal route (e.g. topical), that the vehicle used in many of the clinical studies (Replens®) is not appropriate due to a low release of the steroid and consequently low uptake of P4, and that inhibition of birth is primarily due to inhibition of uterine contractility that can be achieved by supplementation of P4 but not with 17P.

Use of progesterone and progestin analogs for inhibition of preterm birth and other uterine contractility disorders.

In this paper we focus on preterm birth as a uterine contractility disorder caused by hypercontractility of the -myometrium. We describe changes in uterine function during term and preterm labor and delivery. We also examine the usefulness of measurement of uterine electromyographic (EMG) activity, noninvasively monitored from the -abdominal surface of pregnant patients. The use of progesterone treatment for preterm birth is discussed and we conclude that present therapies with progesterone could be improved by changing the route of administration. -Finally we show the results of recent studies that show that progesterone injections completely inhibit uterine EMG activity when given several days to hours before normal delivery. These studies illustrate how progesterone suppresses labor at term or preterm, probably through repression of genes which control excitability and conduction of electrical activity. However, direct profusion of soluble progesterone into the uterine cavity has little immediate inhibitory action and this may demonstrate that progesterone has no direct, nongenomic effects, at least in the rat model used. Further studies are required to determine the effects of progesterone on human uterine EMG activity and whether progesterone treatments will prevent preterm birth.

Inhibitory effects of electrical stimulation on delivery in pregnant rats.

OBJECTIVE: To study the efficacy of uterine electrical stimulation (ES) with various parameters in delaying delivery in term- and preterm-laboring animals. STUDY DESIGN: Catheters and electrodes, as well as ES electrodes, were sutured onto the uterine horn in day-15 pregnant rats. ES with various durations/frequencies (five sets of parameters) was tested from gestation day 21 to determine its effects on uterine contractility. The best set of ES parameters was applied in term (day 21) and preterm (day 18-labor induced) animals to determine the effects of ES on delivery. RESULTS: (1) Significant reduction in uterine contractions (0.54+/-0.11 vs. 0.86+/-0.08 contractions per minute, P<0.001) was noted with ES of only one of the five sets of parameters (set #5 with pulse train of 10s on and 10s off, 28ms pulse width, frequency of 30Hz and amplitude of 4mA); (2) ES with parameter set 5 delayed delivery by 12.5h (P=0.01) and reduced area under the curve of intrauterine pressure in mmHgs (311+/-147.21 vs. 848.75+/-350.38, P<0.05) and AUC-electromyographic activity is area under rectified (i.e. absolute value) uterine EMG trace in mVs (145.25+/-93.1 vs. 410+/-182.46, P<0.05) in the term rats; and (3) similar effects were noted with ES in preterm rats with a delay in delivery by 28h (P<0.001), and a decrease in IUP-AUC (intrauterine pressure-area under curve) (101.5+/-55.45 vs. 551+/-269.06, P=0.017) and EMG-AUC (64.25+/-43.63 vs. 172.5+/-62.91, P=0.03). CONCLUSION: ES of the uterus with appropriate parameters inhibits uterine contractions and delays delivery in both term and preterm rats.

Progesterone, but not luteal estrogen, is required for the establishment of pregnancy in the new world monkey Cebus apella.

The aim of this study was to examine the requirement of luteal progesterone or luteal estrogen for the establishment of pregnancy in the Cebus monkey and to test in a primate species the synergism between RU 486 and letrozole (LTZ) found in rodents for inhibiting implantation. Exposure of target tissues to either hormone was suppressed during the mid-luteal phase of mating cycles by subcutaneous administration of the antiprogestin (RU 486), the aromatase inhibitor LTZ or the antiestrogen (ICI 182780) on days 4-7 of the luteal phase. Administration of 0.1 or 0.5 mg/kg of LTZ on days 5-7 of the luteal phase caused a profound drop in the levels of E(2) in all animals, whereas administration of ICI 182780 0.2 mg/kg on days 4-6 of the luteal phase had the opposite effect. The pregnancy rate in vehicle treated cycles of the same females was (58.3%). Treatment with RU 486, 0.8 mg/kg/day on days 5-7 of the luteal phase-induced endometrial bleeding in 3/5 mated females none of which became pregnant, whereas pregnancy was confirmed in one of the two animals that did not bled. Treatment with RU 486, 0.4 mg/kg/day alone or with LTZ on days 5-7 or ICI 182780 alone, on days 4-6 of the luteal phase failed to induce bleeding, allowing the establishment of pregnancy in 50.0-66.6% of the animals in these groups. We conclude that in Cebus monkeys, progesterone but not luteal estradiol is required for the establishment of pregnancy and that RU 486 and LTZ do not exhibit in this species the synergism found in rodents.

Nursing and nursing education in Iraq: challenges and opportunities.

BACKGROUND: There has been extensive damage to nursing education and training in Iraq over the last two decades through three international wars, counterinsurgency struggles in the north and south, 13 years of economic sanctions, dictatorship and foreign occupation. Fortunately, there is wide agreement that nursing is a key area for further attention. Many nursing leaders have emigrated and the numbers of nurses working in professional roles in Iraq declined sharply after 1990. ISSUES: The number of nurses per population has always been low in Iraq, and fell off precipitously after foreign workers left. There is less than one nursing staff of any kind for physician today. Few of the nursing staff are qualified to what would be minimal standards of professional practice in many countries. There is a strong educational base for nursing education in three Iraqi universities, but it relates little to other schools or hospitals. Military nurses, now being integrated into the public system of hospital care, are considered to have far more technical skill levels than non-military nurses. ACTIONS: Iraq needs a new generation of well trained nurses to develop primary care and health education activities. Programmes in nursing administration and community health nursing need to be developed. The World Health Organization has supported the development of training centres and short courses for nursing leaders. The former six levels of entry to nursing practice have been streamlined to three. Nursing salaries since the 2003 invasion have been greatly increased. These are good beginnings, and much more remains to be done to restore nursing in Iraq.

Effect of nitric oxide on contractions of uterine and cervical tissues from pregnant rats.

Our objective was to evaluate the role of the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) pathway in rat uterine and cervical contractility at mid- and late gestation. Rings of uterus and cervix from Sprague Dawley rats on day 14 of pregnancy (mid-) and day 21 of pregnancy (late) were equilibrated at 2 g passive tension in organ chambers filled with Krebs-Henseleit solution and bubbled with 5% CO2 in air (37 degrees C, pH approximately 7.4). Rings were treated with an inhibitor of outward potassium current, tetraethylammonium, to activate phasic contractions, and the concentration-response relationships to diethylamine/NO and 8-bromo-cGMP (8-br-cGMP) were assessed. Baseline spontaneous activity was significantly higher at term gestation in both uterine and cervical rings compared with mid-gestation. Spontaneous contractile activity was not apparent in cervical rings from rats in mid-gestation, but was persistent after treatment with tetraethylammonium. Oxyhemoglobin did not affect NO-induced inhibition of activation by tetraethylammonium contractile activity in either cervical or uterine tissues in mid- or late gestation. The 8-br-cGMP concentration-dependently inhibited tetraethylammonium-activated contractions that were more pronounced in uterine tissues compared with cervical tissues in both mid- and late gestation. We concluded that activation of the NO-cGMP pathway inhibits both uterine and cervical smooth muscle contractility. Both tissues demonstrated refractoriness to NO at term.

Non-invasive transabdominal uterine electromyography correlates with the strength of intrauterine pressure and is predictive of labor and delivery.

OBJECTIVE: The study was conducted to investigate whether the strength of uterine contractions monitored invasively by intrauterine pressure catheter could be determined from transabdominal electromyography (EMG) and to estimate whether EMG is a better predictor of true labor compared to tocodynamometry (TOCO). STUDY DESIGN: Uterine EMG was recorded from the abdominal surface in laboring patients simultaneously monitored with an intrauterine pressure catheter (n = 13) or TOCO (n = 24). Three to five contractions per patient and corresponding electrical bursts were randomly selected and analyzed (integral of intrauterine pressure; integral, frequency, amplitude of contraction curve on TOCO; burst energy for EMG). The Mann-Whitney test, Spearman correlation and receiver operator characteristics (ROC) analysis were used as appropriate (significance was assumed at a value of p < 0.05). RESULTS: EMG correlated strongly with intrauterine pressure (r = 0.764; p = 0.002). EMG burst energy levels were significantly higher in patients who delivered within 48 h compared to those who delivered later (median [25%/75%]: 96,640 [26,520-322,240] vs. 2960 [1560-10,240]; p < 0.001), whereas none of the TOCO parameters were different. In addition, burst energy levels were highly predictive of delivery within 48 h (AUC = 0.9531; p < 0.0001). CONCLUSION: EMG measurements correlated strongly with the strength of contractions and therefore may be a valuable alternative to invasive measurement of intrauterine pressure. Unlike TOCO, transabdominal uterine EMG can be used reliably to predict labor and delivery.

Expression of inducible nitric oxide synthase messenger RNA, but not guanylate cyclase messenger RNA, depends on gestational age in rat myometrium.

We studied the expression of inducible nitric oxide (NO) synthase (iNOS) and soluble guanylate cyclase (sGC) mRNAs in pregnant rat myometrium. Expression of iNOS and sGC alpha1, beta1 and beta2 mRNA was analyzed in non-pregnant and pregnant (days 10, 14, 17 and 21) Wistar rats by reverse transcription-polymerase chain reaction. Expression of iNOS mRNA increased during pregnancy but decreased on day 21 of gestation. Expression of GC alpha1 mRNA was greater than GC beta1 mRNA at all time points. Expression of uterine GC alpha1 and GC beta1 mRNA did not change significantly during pregnancy and did not differ significantly from non-pregnant levels. The values of sGC beta2 mRNA were below the limit of detection. In conclusion, the expression of iNOS mRNA increased during pregnancy in the myometrium and decreased at term, while the expression of sGC mRNA was not affected by pregnancy. Thus, it is the changes in NO production, rather than changes in its target, that are responsible for uterine quiescence during pregnancy and initiation of labor.

Nitric oxide and its role during pregnancy: from ovulation to delivery.

Nitric oxide (NO) is a major paracrine mediator and important regulatory agent in various female reproductive processes, such as ovulation, implantation, pregnancy maintenance, labor and delivery. Ovulation: Circulating NO-products are increased during follicle development and decreased right after ovulation. INOS-inhibition results in a 50% reduction of ovulation, an effect completely reversed by an NO. Endometrium/Implantation: NO also regulates endometrial functions such as endometrial receptivity, implantation and menstruation. NO-donors may be useful for promoting fertility, while NO-inhibitors might be used for contraception. Uterine contractility: Throughout gestation myometrial NO-production is upregulated thus contributing to achieve uterine quiescence. Close to term, NO-production decreases promoting effective contractions resulting in labor. Clinical trials have demonstrated that NO-donors are effective tocolytics. Cervical ripening: In contrast to the myometrium, NO-production in the cervix is low during gestation and becomes upregulated once pregnancy advances to term. NO-donors are effective and safe cervical ripening agents. This finding from animal studies has been confirmed by several clinical trials. Vasoreactivity: In blood vessels, NO is a potent vasodilator and platelet-aggregation-inhibitor. Lack of NO during gestation was related to the development of pregnancy-induced hypertension and preeclampsia. In conclusion, NO-donors and NOS-inhibitors may provide novel, effective, safe, and inexpensive drugs to regulate and steer various functions in female reproductive life. The benefits reach from contraception to preventing possibly lethal pregnancy complications such as preeclampsia. Introducing NO-donors as tocolytics and cervical ripening agents may contribute to a reduction of fetal and maternal perinatal morbidity and mortality.

Effects of L-type Ca(2+)-channel blockade, K(+)(ATP)-channel opening and nitric oxide on human uterine contractility in relation to gestational age and labour.

Relative uterine inactivity during pregnancy changes to vigorous rhythmic contractility during labour. We hypothesized that mechanisms involved in the regulation of uterine quiescence and contractility differ between term and preterm myometrium and in labour and non-labour states. Myometrial strips, prepared from biopsies taken at Caesarean section from labouring and non-labouring women preterm and at term, were mounted in organ chambers for isometric tension recording. Oxytocin (10(-9) mol/l) was added to maintain stable contractions, and effects of various inhibitors of uterine contractility were studied. The inhibitory effects of L-type Ca(2+)-channel blocker nifedipine and ATP-sensitive K(+)-channel opener pinacidil were greater in myometrium from the non-labour versus the labour group, both preterm and at term. In addition, pinacidil's effect was greater at term compared with preterm in the non-labour group. Mg(2+) and the nitric oxide donor sodium nitroprusside significantly inhibited contractility in all groups without significant differences with regard to labour or gestational age. Decreased inhibition of human uterine contractility by L-type Ca(2+)-channel blockers and K(+)(ATP)-channel openers in preterm and term labour may reflect changes in expression and activity of these channels. Effects of nitric oxide and Mg(2+) are not affected by gestational age or labour.

Uterine electromyography and light-induced fluorescence in the management of term and preterm labor.

OBJECTIVE: Understanding the physiology of the uterus and cervix during term and preterm parturition is crucial for developing methods to control their function and is essential to solving clinical problems related to labor. To date, only crude, inaccurate, and subjective methods are used to assess changes in uterine and cervical function in pregnancy. METHODS: In the past several years, we have developed noninvasive methods to quantitatively evaluate the uterus and cervix based on recording of uterine electrical signals from the abdominal surface (uterine electromyography) and measurement of light-induced fluorescence (LIF) of cervical collagen (Collascope), respectively. Both methods are rapid and allow immediate assessment of uterine contractility and cervical ripening. RESULTS: Studies in animals and humans indicated that uterine and cervical performance can be monitored successfully during pregnancy using those approaches and that these techniques can be used during labor to better define management in a variety of conditions associated with labor. CONCLUSION: The potential benefits of the proposed instrumentation and methods include reducing the rate of preterm delivery, improving maternal and perinatal outcome, monitoring treatment, decreasing cesarean rate and providing research methods to understand uterine and cervical function.

Gender differences in contractile and relaxing responses of aortic rings from lipopolysaccharide-treated rats.

Aortic rings from male and female Sprague-Dawley rats were placed in organ chambers filled with Krebs solution, and the isometric tension was recorded. There were no gender differences in responses to potassium chloride or phenylephrine in either intact or endothelium-denuded rings from control animals. Treatment with 10 mg/kg of lipopolysaccharide (LPS) attenuated the contractile response to potassium chloride in intact, but not in endothelium-denuded rings, and suppressed the phenylephrine contractions in rings both with and without endothelium from male and female rats. Endothelium-dependent and--independent relaxation by acetylcholine and the nitric oxide donor diethylamine/NO, respectively, did not depend on gender and were equally suppressed by LPS treatment. Treatment with LPS accentuated the effects of oxyhemoglobin in rings with and without endothelium and this was significantly larger in rings from females compared to males. Thus, gender differences were present in the effect of LPS on vascular responses. LPS induced a greater inhibition of depolarization by potassium chloride, but not receptor-activated contractions, in aortic rings from female verus male rats.

Calcitonin gene-related peptide dilates the pregnant rat uterine vascular bed via guanylate cyclase, ATP- and Ca-sensitive potassium channels and gap junctions.

We studied the mechanism of calcitonin gene-related peptide (CGRP)-induced vasorelaxation in isolated uterine vascular beds of pregnant rats. The vascular beds were perfused in situ with Krebs buffer containing dextran and indomethacin, an inhibitor of cyclooxygenase. Baseline perfusion pressure was maintained with norepinephrine. When applied as a bolus, CGRP caused a decreased perfusion pressure in uterine vascular beds that was dose-dependent and equal in both mid-pregnant and late-pregnant rats. The non-selective inhibitor of nitric oxide synthase (NOS), Nomega-nitro-L-arginine methyl ester (L-NAME), did not significantly affect CGRP-induced vasodilatation in vascular beds of either group. CGRP-induced vasodilatation was not influenced by preincubation with the inhibitors of adenylate cyclase (SQ 22536 or MDL 12330A), but was significantly attenuated by the selective inhibitor of soluble guanylate cyclase (ODQ). The vasorelaxant effect of CGRP was not significantly influenced by the inhibitor of voltage-gated potassium (KV) channels (4-aminopyridin), but was significantly attenuated by an inhibitor of calcium-regulated potassium (KCa) channels (tetraethylammonium) and by an inhibitor of adenosine triphosphate-sensitive potassium (KATP) channels (glibenclamide). The gap junction uncoupling agent (carbenoxolone) also significantly attenuated the CGRP-induced decrease in perfusion pressure. We conclude that vasorelaxation induced by CGRP in the pregnant rat uterine vascular bed is not dependent on endothelial nitric oxide. In the uterine circulation of late-pregnant rats, the CGRP effect involves activation of soluble guanylate cyclase, but not adenylate cyclase, and does involve KCa and KATP channels and gap junctions.

The effects of cervical application of inhibitors of inducible nitric oxide synthase, cyclooxygenase-1, and cyclooxygenase-2 on delivery in rats.

OBJECTIVE: To investigate the effect of cervical application of nonselective and selective inhibitors of nitric oxide synthases--N-nitro-L-arginine methyl ester, L-N-iminoethyl-lysine, and aminoguanidine--as well as inhibitors of cyclooxygenases--indomethacin, and nimesulide--on timing of delivery and fetal death and disease in pregnant rats. STUDY DESIGN: In a series of experimental protocols, timed-pregnant Sprague-Dawley rats (length of pregnancy, 22 days) were randomly allocated to daily cervical applications of (1) 0.04 mg (n = 6), 0.4 mg (n = 6), 4 mg (n = 6), or 40 mg (n = 6) L-N-iminoethyl-lysine or vehicle (n = 12) on days 19 to 22 of pregnancy; (2) 50 mg aminoguanidine (n = 6), 150 mg aminoguanidine (n = 6), or vehicle (n = 10) on days 19 to 22 of pregnancy; (3) 3 mg indomethacin (n = 6) or vehicle (n = 6) on days 19 to 22 of pregnancy; (4) 12.5 mg/kg nimesulide (n = 8), 25 mg/kg nimesulide (n = 8), 50 mg/kg nimesulide (n = 12), or vehicle (n = 12) on days 19 to 22 of pregnancy and 50 mg/kg nimesulide (n = 23) or vehicle (n = 23) on days 14 to 22 of pregnancy; (5) 50 mg/kg nimesulide (n = 10), 50 mg aminoguanidine plus 50 mg/kg nimesulide (n = 10), 50 mg aminoguanidine (n = 10), or vehicle (n = 10) on days 14 to 22 of pregnancy. The following variables were evaluated: proportion of animals that were delivered on day 23, time to delivery of the first pup (midnight on day 22 was considered to be 0 hour), number of stillborn pups, and average pup weight of each litter. RESULTS: Unlike L-N-iminoethyl-lysine, aminoguanidine, and indomethacin, 50 mg/kg nimesulide applied on the cervix daily for 8 days significantly increased the proportion of animals that were delivered on day 23 (18 of 23 versus 7 of 23; P =.003) and the time to delivery of the first pup by a mean of 10.8 hours (P <.001). Shorter treatment with nimesulide for 4 days increased only the time to delivery of the first pup at the 25-mg/kg dosage (P =.008). Simultaneous application of aminoguanidine and nimesulide significantly (P =.008) prolonged pregnancy to a degree similar to nimesulide alone. The experiment with N-nitro-L-arginine methyl ester was aborted because of severe maternal side effects. Unlike pups in the L-N-iminoethyl-lysine, aminoguanidine, and nimesulide groups, significantly more pups in the indomethacin group died in utero compared with the control group (36.1% versus 3.1%; P <.001), and the surviving pups had lower birth weights (P <.001). CONCLUSIONS: In an animal model, nimesulide was effective in delaying the onset of labor, was well tolerated during pregnancy, and affected cervical ripening directly independent of progesterone withdrawal. Conversely, cervical application of nitric oxide synthase and nonselective cyclooxygenase inhibitors do not extend the duration of pregnancy in the dosages studied, and some are associated with significant adverse effects in the mothers and fetuses.

Methods and devices for the management of term and preterm labor.

In this review, we outline studies showing that the uterus (myometrium) and cervix pass through a conditioning step in preparation for labor. This step is not easily identifiable with present methods designed to assess the uterus or cervix. In the uterus, this seemingly irreversible step consists of changes in the electrical properties that make muscle more excitable and responsive and produce forceful contractions. In the cervix, the step consists of softening of the connective tissue components. Progesterone and nitric oxide appear to have important roles in these processes. The progress of labor can be assessed noninvasively using electromyographic (EMG) signals from the uterus (the driving force for contractility) recorded from the abdominal surface. Uterine EMG bursts detected in this manner characterize uterine contractile events during human and animal pregnancy. A low uterine EMG activity, measured transabdominally throughout most of pregnancy, rises dramatically during labor. EMG activity also increases substantially during preterm labor in humans and rats and may be predictive of preterm labor. A quantitative method for assessing the cervix is also described. A collascope estimates cervical collagen content from a fluorescent signal generated when collagen crosslinks are illuminated with an excitation light of about 340 nm. The system has proved useful in rats and humans at various stages of pregnancy and indicates that cervical softening occurs progressively in the last one-third of pregnancy. In rats, collascope readings correlate with resistance measurements made in the isolated cervix, which may help to assess cervical function during pregnancy and indicate controls and treatments.

The role of endothelium-derived hyperpolarizing factor in the regulation of the uterine circulation in pregnant rats.

OBJECTIVE: The purpose of this study was to determine whether endothelium-derived hyperpolarizing factor regulates rat uterine circulation in pregnant rats. STUDY DESIGN: Intact isolated uterine vascular beds from late pregnant rats were perfused in situ with Krebs buffer that contained dextran, indomethacin, N-nitro-L-arginine methyl ester, and phenylephrine. Endothelium-derived hyperpolarizing factor-induced decreases in perfusion pressure in response to acetylcholine were analyzed. RESULTS: The decrease in perfusion pressure induced by endothelium-derived hyperpolarizing factor was significantly attenuated by 4-aminopyridine and was abolished by a combination of 4-aminopyridine and tetraethylammonium. Endothelium-derived hyperpolarizing factor-induced decrease in perfusion pressure was abolished by potassium chloride and attenuated by miconazole, but not linoleyl hydroxamic acid. Endothelium-derived hyperpolarizing factor-induced decrease in perfusion pressure persisted after perfusion with solutions that contained 2 inhibitors of nitric oxide synthase and a scavenger of nitric oxide. Nitric oxide exerted negative feedback on the endothelium-derived hyperpolarizing factor effects. CONCLUSION: In the pregnant rat uterine vascular beds, endothelium-derived hyperpolarizing factor release is activated by a delayed rectifier type of voltage-sensitive potassium channel. Endothelium-derived hyperpolarizing factor does not seem to be related to nitric oxide or to products of lipoxygenase or cytochrome p450 mono-oxygenase pathways of arachidonic acid metabolism.