Fisiolog+¡a de Las Contracciones Uterinas

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Clin Perinatol 30 (2003) 665 – 676

The physiology of uterine contractions


Holger Maul, MD, MMSa, William L. Maner, BSca,
George R. Saade, MDa, Robert E. Garfield, PhDa,b,*
a
Division of Reproductive Sciences, Department of Obstetrics & Gynecology,
University of Texas Medical Branch, 301 University Blvd. Galveston, TX 77555, USA
b
Zentrum für Frauenheilkunde, Hannover Medical School (MHH), Hannover, Germany

Understanding the physiology of the uterus during term and preterm parturition
is important for developing methods to control uterine function and is essential to
solving clinical problems related to labor. To date, only inaccurate and subjective
methods have been used to assess gestational changes in uterine function. To
quantitatively evaluate the uterine activity, the authors in the past several years
developed noninvasive methods based on recording of uterine electrical signals
from the abdominal surface uterine electromyography (EMG), a method that
allows reliable and immediate assessment of uterine contractility. Studies in
animals and humans indicate that uterine performance can be successfully
monitored during pregnancy using EMG. EMG might be used to better define
management for a variety of conditions associated with labor. The potential
benefits of the proposed instrumentation and method include: reducing the rate
of preterm delivery, improving maternal and perinatal outcome, monitoring
treatment, decreasing cesarean section rate, and providing research methods to
understand uterine function.
Labor is the physiologic process by which a fetus is expelled from the uterus to
the outside world and is defined as regular uterine contractions accompanied by
cervical effacement and dilatation [1]. For normal labor at term, biochemical
changes in the cervical connective tissue usually precede uterine contractions and
cervix dilatation. Preterm labor, defined as labor before 37 weeks of gestation—the
most common obstetrical complication—occurs in about 20% of pregnant women.
In the United States alone, 10% of the four million neonates born each year are

The studies described in this review article were supported by NIH Grant 5 R01 HD37480. The
authors also acknowledge the support of the General Clinical Research Center (GCRC) at the
University of Texas Medical Branch, funded from Grant M01 RR00073 from the National Center for
Research Resources, NIH, USPHS.
* Corresponding author. Department of Obstetrics and Gynecology, The University of Texas
Medical Branch, 301 University Blvd. Galveston, TX 77555.
E-mail address: rgarfiel@utmb.edu (R.E. Garfield).

0095-5108/03/$ – see front matter D 2003 Elsevier Inc. All rights reserved.
doi:10.1016/S0095-5108(03)00105-2
666 H. Maul et al / Clin Perinatol 30 (2003) 665–676

premature [2,3]. At $1500 a day for neonatal intensive care, this constitutes a
national-health-care expenditure well over $5 billion [4]. In addition, preterm labor
accounts for 85% of infant mortality and 50% of the surviving infants’ neurologic
disorders. Current tocolytic therapy has not decreased the rate of preterm delivery.
It is argued that the failure of the current strategies to decrease the rate of preterm
labor may be because of the fact that, once preterm labor is diagnosed, any
therapeutic benefit is lost or temporary. Therefore, one of the keys to treating
preterm labor would be early detection or prediction.
Recently, the authors developed a noninvasive method for the objective
evaluation of the status of the uterus. It consists of recording EMG signals from
the abdominal surface. Because action potentials are responsible for contractility
of the uterus, recording of EMG activity can be used to assess the contractile
function of the uterus. This method has been validated in animals, and preliminary
studies in humans support its clinical use. EMG may supplement or replace the
methods used currently to assess uterine function (tocodynamometry, intrauterine
pressure catheter).

Diagnosis of labor
To date, labor remains a clinical diagnosis. While several methods (described
later) have been adopted to monitor labor, they are indirect or subjective and do not
provide accurate differentiation between true and false labor or knowledge of when
labor will occur. Presently, the most important key to preventing preterm labor has
been constant contact and care from health-care practitioners [5]. While some
methods can identify signals of ongoing labor, none of the methods offer objective
data that accurately predict labor. The methods range in complexity from simple
self-awareness of contractions to complex electronic pressure sensors. Table 1 lists
the current methods and their characteristics. The current state of the labor-
monitoring art can be summarized as follows: (1) current methods are indirect or
subjective; (2) the intrauterine-pressure catheter provides the best information, but
its use is limited by invasiveness and need for ruptured membranes; (3) the
currently available external – uterine-activity monitor (tocodynamometer or
‘‘toco’’) is uncomfortable and inaccurate; (4) no method has been reliable at
predicting preterm labor; (5) no method has lead to an effective treatment of
preterm labor.

Table 1
Current methods used in monitoring uterine function
Accuracy Invasive
Monitoring of contractions in combination Moderate No
with pelvic examination
Symptomatic self monitoring Low No
Intrauterine pressure monitor High Yes
External uterine monitor (tocodynamometer) Erratic No
H. Maul et al / Clin Perinatol 30 (2003) 665–676 667

Of the current methods, intrauterine pressure catheters perhaps provide the best
information concerning uterine contractions, but their invasiveness can increase the
risk of infection and insertion requires rupture of the membranes. Moreover,
intrauterine pressure catheters do not provide any information regarding cervical
function. Tocodynamometers are external pressure measurement devices, which
are used to detect changes in abdominal contour as an indirect indication of uterine
contractions. The primary advantage of a tocodynamometer is that it does not
require an invasive probe. This allows the device to be used for most pregnancies
without risk to the fetus or the mother. External toco monitoring devices are used in
over 90% of all hospital births in the United States. Physicians have been quick to
adopt these devices, because they supply uterine-contraction data with little risk.
However, these instruments have not changed treatments for preterm labor. Toco
devices have one major drawback: accuracy. Many different variables affect the
measurement of uterine contractions, such as instrument placement, amount of
subcutaneous fat, and uterine wall pressure. Additionally, the use of external
tocodynamometry is limited to obtaining the frequency of contractions and does
not include any direct or indirect measure of functional interest, such as strength or
efficiency of the contractions. Yet the advantage of a noninvasive method in
providing uterine contraction data has led to its widespread adoption, despite these
limitations. Home uterine activity monitoring (HUAM), which is based on external
tocodynamometer recordings, has been used to predict preterm labor [6– 8]. In a
recent study, however, HUAM was no better in lowering the frequency of preterm
birth than was weekly contact with a nurse [9].
Despite all the limitations summarized earlier in this discussion, the presence of
uterine contractions and cervical softening at 28 weeks’ gestation were the best
predictors of spontaneous preterm birth in a group of nulliparous women at risk for
preterm delivery [10]. The authors believe that the issue is not whether changes in
uterine activity precede labor, but rather finding the appropriate method to detect
these changes.

The myometrium

Electrical properties of the myometrium


The sequence of contraction and relaxation of the myometrium results from the
cyclic depolarization and repolarization of the muscle-cell membranes. The
spontaneous electrical discharges from the myometrium consist of intermittent
bursts of spike-like action potentials [11– 17]. Uterine volume (chronic stretch) and
ovarian hormones (principally estrogen) contribute to the change in action potential
shape, through their effects on the resting membrane potential [18 – 20]. A single
spike can initiate a contraction, but multiple, coordinated spikes are needed for
forceful and sustained contractions [13]. As in other excitable tissues, the action
potential in uterine smooth muscle results from voltage- and time-dependent
changes in membrane ionic permeability [21].
668 H. Maul et al / Clin Perinatol 30 (2003) 665–676

Fig. 1. EMG activity recorded directly from the uterus (top) and intrauterine pressure (bottom)
obtained from a pregnant rat during labor.

Studies of isolated myometrial tissues using microelectrodes or extracellular


electrodes demonstrate the temporal association between electrical events and
contractions [22 –35]. In all species studied, each contraction is accompanied by a
burst of action potentials (Fig. 1), which start slightly earlier than the contraction.
The frequency, amplitude, and duration of contractions are determined respectively
by the frequency of the action potentials within a burst, the duration of a burst, and
the total number of cells that are simultaneously active [13]. The frequency of the
action potentials within a burst first increases and then decreases. The burst stops
before the uterus relaxes [13]. The electrical and mechanical activities of the
myometrium have been recorded by many investigators [23 –31,36] with various
species of intact animals, including humans [32 – 35,37].
The authors’ studies to date, and those of other investigators [38 –42], provide
convincing evidence that uterine EMG activity can be accurately assessed from
abdominal surface measurements.

Changes in electrical properties of the myometrium during pregnancy and


labor
The authors and other investigators, have shown that myometrial cells are
coupled together electrically by gap junctions composed of connexin proteins
[43,44]. The grouping of connexins provides channels of low electrical resistance
between cells and thereby furnishes pathways for the efficient conduction of action
potentials. Throughout most of a pregnancy, and in all species studied, these cell-
to-cell channels or contacts are few, indicating poor coupling and decreased
electrical conductance. This condition favors quiescence of the muscle and the
maintenance of pregnancy. At term, however, the number of cell junctions
H. Maul et al / Clin Perinatol 30 (2003) 665–676 669

increases and they form an electrical syncytium required for effective contractions.
The presence of the contacts seems to be controlled by changing estrogen and
progesterone levels in the uterus [43]. As action potentials propagate over the
surface of a myometrial cell, the depolarization causes voltage-dependent Ca2 +
channels (VDCC) to open. When this occurs, Ca2 + enters the muscle cell, flowing
down its chemical gradient, to activate the myofilaments and evoke a contraction.
The authors recently demonstrated by RT-PCR that the expression of VDCC
subunits in the rat myometrium increases during both term and preterm labor [45].
This increased expression, which seems to be controlled by progesterone with-
drawal, may facilitate uterine contractility during labor by increasing the number of
cell-membrane portals for Ca2 + entry.

A model of labor—a preparatory stage


Progesterone seems to exert an overall control of uterine quiescence by: (1)
suppressing a number of genes in the myometrium that are essential for uterine
contractility (connexin 43, calcium channels, receptors, etc.); (2) up-regulating the
relaxation mechanisms, including the nitric oxide system [46,47]; and (3) sup-
pressing the release of proinflammatory cytokines, thereby reducing the production
of prostaglandins [48,49]. The results of experimental and clinical studies with
progesterone and its antagonists indicate that parturition is composed of two major
steps: a long conditioning (preparatory) phase, followed by a short secondary phase
(active labor) [42,44,46,50,51] (Fig. 2). Similar models have been proposed by
other investigators [52]. The conditioning step leading to the softening of the cervix
takes place during a different time frame from that of the uterus. In the
myometrium, this preparatory process involves changes in transduction mecha-
nisms and the synthesis of several new proteins, including connexins, ion channels,
and receptors for uterotonins. At the same time, there is a down-regulation of the
nitric oxide system that leads to withdrawal of uterine relaxation. The authors view

Fig. 2. Working model for the initiation of labor showing changes in the uterus (myometrium), cervix,
and fetal membranes. Major alterations occur in these tissues during a conditioning or preparatory step.
670 H. Maul et al / Clin Perinatol 30 (2003) 665–676

the initiation of the conditioning step as the start of parturition. The conditioning
phase can be induced with antiprogestins in all species studied thus far, including
primates [50]. At some point during the conditioning step, the process becomes
irreversible and leads to active labor and delivery. Once active labor has started,
delivery generally cannot be delayed in humans, because the changes that have
occurred in the preparatory phase are by this time well-established and thus not
reversible, at least usually not with currently available tocolytics. Active labor,
leading eventually to the delivery of the fetus and placenta, starts with the onset of
coordinated uterine contractions. In the authors’ opinion, the key to understanding
parturition and developing suitable treatment methods is the understanding of the
processes by which the myometrium undergoes these conditioning or conversion
stages (see Fig. 2). Unfortunately, the currently available methods, which are based
solely on monitoring contractions, do not detect whether a patient has entered the
conditioning step, because changes in these parameters may be independent of this
preparatory stage and may occur much later.

Electromyographic signals-recordings are representative of uterine


contractile activity

Studies in rats
The authors recently recorded uterine EMG activity directly and simultaneously
from the uterine and abdominal surfaces of pregnant rats, while also monitoring
intrauterine pressure [38,39]. Early in pregnancy, and until about day 18 of
gestation (usual length of gestation 21– 23 days), EMG bursts were irregular and
of low amplitude. There was also little or no correspondence between activity
recorded from the uterus and the abdominal surface. Increases in intrauterine
pressure activity were frequent, but still irregular and generally of low amplitude.
Later in gestation (day 21 to delivery) the EMG activity became more regular, and
the signals directly recorded from the uterus coincided well with those recorded
from the abdominal surface (Fig. 3). There was also a tendency for intrauterine

Fig. 3. Expanded views of EMG bursts from rats recorded simultaneously from uterine (Ut) and
abdominal (AS) surface, along with IUP, during term delivery (Data from Buhimschi C, Boyle MB,
Saade GR, Garfield RE. Uterine activity during pregnancy and labor assessed by simultaneous
recordings from the myometrium and abdominal surface in the rat. Am J Obstet Gynecol 1998;178:
811 – 22).
H. Maul et al / Clin Perinatol 30 (2003) 665–676 671

pressure waves to correspond in time with the EMG activity recorded from the
uterus, as well as from the abdominal surface. During term and preterm labor in
rats, EMG activity recorded from both the uterus and abdominal surface occurred
concurrently with changes in intrauterine pressure (see Fig. 3). At this stage, the
electromyographic signals and the intrauterine pressure waves were frequent
(about one contraction per minute) and of high amplitude.
The authors’ study demonstrated that abdominal surface recordings of uterine
electrical events are representative of the electrical activity of the uterus. This
conclusion is based on the following observations: (1) action potential bursts
obtained from the abdominal surface almost perfectly mirror bursts occurring in the
myometrium; (2) increases and decreases in electrical bursts at both sites accom-
pany similar changes in intrauterine pressure; (3) changes in activity during term
and preterm labor are detected simultaneously from both the uterus and the
abdominal surface; (4) either pharmacologic stimulation or inhibition results in
similar changes in recordings from both sites [40]; (5) cardiac action potentials do
not interfere with either uterine or abdominal recordings. These studies suggested
that EMG recordings could be used to determine when the uterus enters the
electrical state required for labor.
The authors also evaluated the EMG signals from the uterine and abdominal
surface by power density spectral and wavelet analysis [39]. These studies
indicated that several types of algorithms are useful in evaluating the EMG activity
recorded from the maternal abdominal surface. The authors also demonstrated
increases in all the following parameters during the gestational period leading to
labor: amplitude and power of bursts, high-frequency content of action potential
waveforms, rate of burst production, and duration of bursts [39]. The increase in
energy of the electrical activity and in the high-frequency content of the action
potentials are the result of the changes that occur in the electrical properties of the
myometrium during term and preterm labor, and that are aimed at increasing
current flow (and contractile force) in the myometrial smooth muscle. These
changes seem to occur during late gestation, with the maximal increase occurring
during labor. These data provide convincing evidence that EMG activity can be
accurately recorded from the abdominal surface of pregnant rats. In addition,
analysis of transabdominally-recorded rat-uterine electrical activity allows for the
monitoring of a number of important parameters and is not limited, as is the case
with external tocodynamometry, to frequency of contractions.

Studies of humans
The authors also recently evaluated the possibility that human uterine electrical
events (EMG signals) could be recorded and characterized from the abdominal
surface during pregnancy [39]. The estimated gestational ages of the patients
ranged from 20 to 42 weeks. Gravidas included: those at term but not in labor, those
in active labor (at term and preterm), those who were postpartum, and those
followed longitudinally during pregnancy. Uterine electrical activity was recorded
using two sets of bipolar electrodes placed on the abdominal surface. In some
672 H. Maul et al / Clin Perinatol 30 (2003) 665–676

patients the intrauterine pressure was also measured with a saline-filled catheter
inserted into the uterine cavity. The uterine EMG signals were analyzed in the 0.3 to
50 Hz frequency range and digitized at 200 samples per second. Over 100 patients
were recorded, and evidence of uterine electrical activity was observed in every
case. Power density spectral analysis was performed on some patients using a fast
Fourier transformation of the electrical activity, to assess and characterize the
evolution of uterine electrical activity during pregnancy.
The results of this study showed that there was minimal uterine electrical
activity, consisting of infrequent and low amplitude EMG bursts, throughout most
of pregnancy (Fig. 4). When bursts occurred before the onset of labor, they often
corresponded to periods of perception of contractility by the patient. During term
and preterm labor, bursts of EMG activity were frequent, of large amplitude, and
correlated with the large changes in the intrauterine pressure and pain sensation.
Spectral analysis of the electrical events within bursts recorded during active labor
demonstrated a significantly higher peak frequency compared with before labor. In
addition, electrical activity at different periods of gestation showed a dramatic
increase in the peaks of power levels within the bursts (about three- to four-fold)
during term and preterm labor compared with the power level of electrical activity
recorded early in gestation.
The authors conclude that recording of uterine EMG from the abdominal surface
could be a reliable method to follow the evolution of uterine contractility during
human pregnancy. Analysis of EMG activity might be used to characterize and
evaluate uterine contractions during term and preterm labor. This noninvasive tech-
nology could prove to be useful in the management of labor and its complications.

Fig. 4. EMG activity as recorded from the abdominal surface of pregnant women at 27 weeks
nonlabor, (A) and during term labor (B, C). Note the correspondence between EMG bursts and pain
(arrows, B) and intrauterine pressure IUP (C) during labor. (D) Shows expanded and enlarged view of
a single burst obtained from a nonlabor patient (top) and a patient in labor (bottom) (Data from
Buhimschi C, Boyle MB, Garfield RE. Electrical activity of the human uterus during pregnancy as
recorded from the abdominal surface. Obstet Gynecol 1997;90:102 – 11).
Table 2
Potential clinical use and benefits of abdominal electromyography (EMG)
Preterm Cervical Induction Augmentation Failure
Antepartum Early labor contractions incompetence of labor of labor to progress Tocolysis

H. Maul et al / Clin Perinatol 30 (2003) 665–676


EMG + + + + + + + +
Clinical use Predict preterm Differentiate Determine Rule out the Predict success More objective More objective Predict success
delivery between false need for presence of of induction and accurate and accurate of tocolysis
and true labor tocolysis subclinical uterine More objective analysis of analysis of More objective
electrical activity and accurate uterine activity uterine activity and accurate
analysis of Better way to Determine if analysis of
uterine activity monitor and abnormal uterine uterine activity
adjust oxytocin activity is Improved method
infusion the cause to monitor and
adjust tocolytic
therapy
Potential Prevent preterm Prevent Prevent Better define Prevent Decrease numbers Decrease numbers Prevent
benefits delivery and unnecessary unnecessary use candidates for unnecessary of cesarean sec- of cesarean sec- complications
improve perinatal admissions of tocolytics and post-cerclage prolonged tions due to tions due to from tocolytics
outcome decrease cost tocolysis inductions inappropriate use inappropriate Decrease time
Better of oxytocin use of oxytocin on tocolytics
understanding
of etiologies

673
674 H. Maul et al / Clin Perinatol 30 (2003) 665–676

The authors’ results suggest that parameters such as the percentage of time that
the uterus is electrically active and the power density analysis could indicate how
close a patient is to preterm or term labor. In humans, this method of analysis may
detect whether the stage of uterine preparedness for labor has or has not yet been
achieved. With the aid of EMG recording, monitoring of labor induction or
augmentation may become more objective and accurate. Oxytocin might be started
or increased earlier if needed or the adequacy of uterine contractions might be
ascertained and cesarean section performed sooner than if the health care providers
were relying on external tocodynamometry or had to wait for intrauterine pressure
recording. The authors’ studies offer a possible algorithm that could bring an
improvement in the clinical diagnosis and treatment. It is obvious that more studies
are needed before this technology is ready for clinical use in human subjects, but
these initial data suggest that it has great promise.

Potential clinical applications of uterine electromyographic signals


The authors preliminary data regarding abdominal recordings of uterine EMG
activity suggest that it could prove to be extremely useful for a variety of obstetrical
indications and problems (Table 2) [53,54]. The potential benefits from the use of
such methodology might include the reduction in preterm delivery rate and
improved perinatal outcome, the identification of efficacious treatment regimens,
and a decrease in cesarean-section rate. In addition, this method could be used in
research to define mechanisms that regulate normal and abnormal function of the
uterus and ways to control them pharmacologically.

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