Identification of uterine pacemaker regions at the myometrial-placental interface in the rat.

KEY POINTS: Coordinated contraction of the uterine smooth muscle is essential to parturition. Histologically and physiologically defined pacemaker structures have not been identified in uterine smooth muscle. Here we report combined electrophysiological and histological evidence of zones associated with pacemaker activity in the rat myometrium. Our method relies crucially on the integration of histological and electrophysiological data in an in silico three-dimensional reconstruction of the rat myometrium at 10 µm resolution. We find that myometrial/placental pacemaking zones are closely related with placental sites and the area of disruptive myometrial remodelling surrounding such sites. If analogues of the myometrial/placental pacemaking zone are present in the human, defining their histology and physiology will be important steps towards treatment of pre-term birth, pre-eclampsia, and postpartum haemorrhage. ABSTRACT: Coordinated uterine contractions are essential for delivering viable offspring in mammals. In contrast to other visceral smooth muscles, it is not known where excitation within the uterus is initiated, and no defined pacemaking region has hitherto been identified. Using multi-electrode array recordings and high-resolution computational reconstruction of the three-dimensional micro-structure of late pregnant rat uterus, we demonstrate that electrical potentials are initiated in distinct structures within the placental bed of individual implantation sites. These previously unidentified structures represent modified smooth muscle bundles that are derived from bridges between the longitudinal and circular layers. Coordinated implantation and encapsulation by invading trophoblast give rise to isolated placental/myometrial interface bundles that directly connect to the overlying longitudinal smooth muscle layer. Taken together, these observations imply that the anatomical structure of the uterus, combined with site-specific implantation, gives rise to emergent patterns of electrical activity that drive effective contractility during parturition.

A computational method for three-dimensional reconstruction of the microarchitecture of myometrial smooth muscle from histological sections.

BACKGROUND: The fibrous structure of the myometrium has previously been characterised at high resolutions in small tissue samples (< 100 mm3) and at low resolutions (∼500 µm per voxel edge) in whole-organ reconstructions. However, no high-resolution visualisation of the myometrium at the organ level has previously been attained. METHODS AND RESULTS: We have developed a technique to reconstruct the whole myometrium from serial histological slides, at a resolution of approximately 50 µm per voxel edge. Reconstructions of samples taken from human and rat uteri are presented here, along with histological verification of the reconstructions and detailed investigation of the fibrous structure of these uteri, using a range of tools specifically developed for this analysis. These reconstruction techniques enable the high-resolution rendering of global structure previously observed at lower resolution. Moreover, structures observed previously in small portions of the myometrium can be observed in the context of the whole organ. The reconstructions are in direct correspondence with the original histological slides, which allows the inspection of the anatomical context of any features identified in the three-dimensional reconstructions. CONCLUSIONS AND SIGNIFICANCE: The methods presented here have been used to generate a faithful representation of myometrial smooth muscle at a resolution of ∼50 µm per voxel edge. Characterisation of the smooth muscle structure of the myometrium by means of this technique revealed a detailed view of previously identified global structures in addition to a global view of the microarchitecture. A suite of visualisation tools allows researchers to interrogate the histological microarchitecture. These methods will be applicable to other smooth muscle tissues to analyse fibrous microarchitecture.

The location of pacemakers in the uteri of pregnant guinea pigs and rats.

The pregnant uterus is a smooth muscle organ whose pattern of contraction is dictated by the propagation of electrical impulses. Such electrical activity may originate from one or more pacemakers, but the location of these sites has not yet been determined. To detect the location of the pacemaker in the gravid uterus, two approaches were used: 1) determine the site from where the contraction started using isolated uteri from the pregnant guinea pig, and videotape their contractions; and 2) record, in isolated uteri from pregnant term rats, with 240 extracellular electrodes simultaneously, and determine where the electrical bursts started. In both the contractile and electrophysiological experiments, there was not a single, specific pacemaker area. However, most contractions (guinea pig 87%) and bursts (rat 76%) started close to the mesometrial border (mean 2.7 ± 4.0 mm SD in guinea pigs and 1.3 ± 1.4 mm in rats). In addition, in the rat, most sites of initiations were located closer to the ovarial end of the horn (mean distance from the ovarial end 6.0 ± 6.2 mm SD), whereas such an orientation was not seen in the guinea pig. In both guinea pig and rat uteri at term, there is not one specific pacemaker area. Rather, contractile and electrical activity may arise from any site, with the majority starting close to the mesometrial border. Furthermore, in the rat, most activities started at the ovarial end of the horn. This may suggest a slightly different pattern of contraction in both species.

Recent progress in gastric arrhythmia: pathophysiology, clinical significance and future horizons.

Gastric arrhythmia continues to be of uncertain diagnostic and therapeutic significance. However, recent progress has been substantial, with technical advances, theoretical insights and experimental discoveries offering new translational opportunities. The discoveries that interstitial cells of Cajal (ICC) generate slow waves and that ICC defects are associated with dysmotility have reinvigorated gastric arrhythmia research. Increasing evidence now suggests that ICC depletion and damage, network disruption and channelopathies may lead to aberrant slow wave initiation and conduction. Histological and high-resolution (HR) electrical mapping studies have now redefined the human 'gastric conduction system', providing an improved baseline for arrhythmia research. The application of HR mapping to arrhythmia has also generated important new insights into the spatiotemporal dynamics of arrhythmia onset and maintenance, resulting in the emergence of new provisional classification schemes. Meanwhile, the strong associations between gastric functional disorders and electrogastrography (EGG) abnormalities (e.g. in gastroparesis, unexplained nausea and vomiting and functional dyspepsia) continue to motivate deeper inquiries into the nature and causes of gastrointestinal arrhythmias. In future, technical progress in EGG methods, new HR mapping devices and software, wireless slow wave acquisition systems and improved gastric pacing devices may achieve validated applications in clinical practice. Neurohormonal factors in arrhythmogenesis also continue to be elucidated and a deepening understanding of these mechanisms may open opportunities for drug design for treating arrhythmias. However, for all translational goals, it remains to be seen whether arrhythmia can be corrected in a way that meaningfully improves organ function and symptoms in patients.

The electrical activities of the uterus during pregnancy.

In contrast to the current state of knowledge of cardiac and of gastrointestinal electrophysiology, our current knowledge of the physiology of the uterus during pregnancy is still very rudimentary. Despite seminal work performed in the past decades, there are still significant areas that we know little about. In this review, some of these areas are explored. For example, although many studies have tried to find the site of the uterus pacemaker, such a site has not yet been found and its mechanism and location remain, to date, a mystery. Similarly, there is much confusion as to the mechanism of propagation of the electrical impulse. Although the existence of gap junctions, connecting neighboring myometrial cells to each other, have been known since 1977, alternative or additional mechanisms are being suggested such as the potential existence of a network of interstitial cells, similar to the one that is functioning in the gut, or the involvement of stretch receptors to synchronize activity and contraction. In recent years, high-resolution studies have been introduced enabling detailed analysis of the location and spatial patterns of propagation. This work is being developed at the in-vitro level in isolated tissues, in the whole organ and in several animal species. Most recently, a surge in new technology enabling high fidelity and high resolution recording from the human uterus through the abdominal wall are being explored which could ultimately lead to new diagnostic tools and a clearer understanding of the physiology of pregnancies and (premature) labor.

Abnormal initiation and conduction of slow-wave activity in gastroparesis, defined by high-resolution electrical mapping.

BACKGROUND & AIMS: Interstitial cells of Cajal (ICC) generate slow waves. Disrupted ICC networks and gastric dysrhythmias are each associated with gastroparesis. However, there are no data on the initiation and propagation of slow waves in gastroparesis because research tools have lacked spatial resolution. We applied high-resolution electrical mapping to quantify and classify gastroparesis slow-wave abnormalities in spatiotemporal detail. METHODS: Serosal high-resolution mapping was performed using flexible arrays (256 electrodes; 36 cm(2)) at stimulator implantation in 12 patients with diabetic or idiopathic gastroparesis. Data were analyzed by isochronal mapping, velocity and amplitude field mapping, and propagation animation. ICC numbers were determined from gastric biopsy specimens. RESULTS: Mean ICC counts were reduced in patients with gastroparesis (2.3 vs 5.4 bodies/field; P < .001). Slow-wave abnormalities were detected by high-resolution mapping in 11 of 12 patients. Several new patterns were observed and classified as abnormal initiation (10/12; stable ectopic pacemakers or diffuse focal events; median, 3.3 cycles/min; range, 2.1-5.7 cycles/min) or abnormal conduction (7/10; reduced velocities or conduction blocks; median, 2.9 cycles/min; range, 2.1-3.6 cycles/min). Circumferential conduction emerged during aberrant initiation or incomplete block and was associated with velocity elevation (7.3 vs 2.9 mm s(-1); P = .002) and increased amplitudes beyond a low base value (415 vs 170 µV; P = .002). CONCLUSIONS: High-resolution mapping revealed new categories of abnormal human slow-wave activity. Abnormalities of slow-wave initiation and conduction occur in gastroparesis, often at normal frequency, which could be missed by tests that lack spatial resolution. Irregular initiation, aberrant conduction, and low amplitude activity could contribute to the pathogenesis of gastroparesis.

Functional reentry and circus movement arrhythmias in the small intestine of normal and diabetic rats.

In a few recent studies, the presence of arrhythmias based on reentry and circus movement of the slow wave have been shown to occur in normal and diseased stomachs. To date, however, reentry has not been demonstrated before in any other part of the gastrointestinal system. No animals had to be killed for this study. Use was made of materials obtained during the course of another study in which 11 rats were treated with streptozotocin and housed with age-matched controls. After 3 and 7 mo, segments of duodenum, jejunum, and ileum were isolated and positioned in a tissue bath. Slow wave propagation was recorded with 121 extracellular electrodes. After the experiment, the propagation of the slow waves was reconstructed. In 10 of a total of 66 intestinal segments (15%), a circus movement of the slow wave was detected. These reentries were seen in control (n = 2) as well as in 3-mo (n = 2) and 7-mo (n = 6) diabetic rats. Local conduction velocities and beat-to-beat intervals during the reentries were measured (0.42 ± 0.15 and 3.03 ± 0.67 cm/s, respectively) leading to a wavelength of 1.3 ± 0.5 cm and a circuit diameter of 4.1 ± 1.5 mm. This is the first demonstration of a reentrant arrhythmia in the small intestine of control and diabetic rats. Calculations of the size of the circuits indicate that they are small enough to fit inside the intestinal wall. Extrapolation based on measured velocities and rates indicate that reentrant arrhythmias are also possible in the distal small intestine of larger animals including humans.

Slow wave propagation and plasticity of interstitial cells of Cajal in the small intestine of diabetic rats.

The number of myenteric interstitial cells of Cajal (ICC-MY), responsible for the generation and propagation of the slow wave in the small intestine, has been shown to decrease in diabetes, suggesting impairment of slow-wave (SW) propagation and related motility. To date, however, this expected decrease in SW propagation has neither been recorded nor analysed. Eleven rats were treated with streptozotocin and housed in pairs with 11 age-matched control animals. After 3 or 7 months, segments of duodenum, jejunum and ileum were isolated and divided into two parts. One part was processed for immediate freezing, cryosectioning and immunoprobing using anti-c-Kit antibody to quantify ICC-MY. The second part was superfused in a tissue bath, and SW propagation was recorded with 121 extracellular electrodes. In addition, a cellular automaton was developed to study the effects of increasing the number of inactive cells on overall propagation. The number of ICC-MY was significantly reduced after 3 months of diabetes, but rebounded to control levels after 7 months of diabetes. Slow-wave frequencies, velocities and extracellular amplitudes were unchanged at any stage of diabetes. The cellular automaton showed that SW velocity was not linearly related to the number of inactive cells. The depletion of ICC-MY is not as severe as is often assumed and in fact may rebound after some time. In addition, at least in the streptozotocin model, the initial reduction in ICC-MY is not enough to affect SW propagation. Diabetic intestinal dysfunction may therefore be more affected by impairments of other systems, such as the enteric system or the muscle cells.

Toward a concept of stretch coupling in smooth muscle: a thesis by Lars Thuneberg on contractile activity in neonatal interstitial cells of Cajal.

The hypothesis was put forward by Thuneberg that rhythmically contracting interstitial cells of Cajal (ICC) were sensing stretch of the musculature and that this information was transmitted to smooth muscle cells via peg and socket contacts. The present study provides the evidence for the contractile nature of ICC as perceived by Thuneberg. The contractile activity is shown by video frame subtraction and by tracking areas of interest in sequential video frames. Thuneberg used neonatal ICC in culture maintained between two coverslips thereby allowing growth factors to quickly reach optimal concentrations. Contractions of ICC were seen to precede smooth muscle contractions. In addition, strong contractions were observed solely in branches of ICC. It is hoped that this communication will stimulate discussion about the contractile nature of ICC and that this phenomenon will eventually find its place amongst the physiological properties of the ICC networks of the gut musculature.

Origin and propagation of human gastric slow-wave activity defined by high-resolution mapping.

Slow waves coordinate gastric motility, and abnormal slow-wave activity is thought to contribute to motility disorders. The current understanding of normal human gastric slow-wave activity is based on extrapolation from data derived from sparse electrode recordings and is therefore potentially incomplete. This study employed high-resolution (HR) mapping to reevaluate human gastric slow-wave activity. HR mapping was performed in 12 patients with normal stomachs undergoing upper abdominal surgery, using flexible printed circuit board (PCB) arrays (interelectrode distance 7.6 mm). Up to six PCBs (192 electrodes; 93 cm(2)) were used simultaneously. Slow-wave activity was characterized by spatiotemporal mapping, and regional frequencies, amplitudes, and velocities were defined and compared. Slow-wave activity in the pacemaker region (mid to upper corpus, greater curvature) was of greater amplitude (mean 0.57 mV) and higher velocity (8.0 mm/s) than the corpus (0.25 mV, 3.0 mm/s) (P < 0.001) and displayed isotropic propagation. A marked transition to higher amplitude and velocity activity occurred in the antrum (0.52 mV, 5.9 mm/s) (P < 0.001). Multiple (3-4) wavefronts were found to propagate simultaneously in the organoaxial direction. Frequencies were consistent between regions (2.83 +/- 0.35 cycles per min). HR mapping has provided a more complete understanding of normal human gastric slow-wave activity. The pacemaker region is associated with high-amplitude, high-velocity activity, and multiple wavefronts propagate simultaneously. These data provide a baseline for future HR mapping studies in disease states and will inform noninvasive diagnostic strategies.

High-resolution entrainment mapping of gastric pacing: a new analytical tool.

Gastric pacing has been investigated as a potential treatment for gastroparesis. New pacing protocols are required to improve symptom and motility outcomes; however, research progress has been constrained by a limited understanding of the effects of electrical stimulation on slow-wave activity. This study introduces high-resolution (HR) "entrainment mapping" for the analysis of gastric pacing and presents four demonstrations. Gastric pacing was initiated in a porcine model (typical amplitude 4 mA, pulse width 400 ms, period 17 s). Entrainment mapping was performed using flexible multielectrode arrays (

A novel laparoscopic device for measuring gastrointestinal slow-wave activity.

BACKGROUND: A periodic electrical activity, termed "slow waves", coordinates gastrointestinal contractions. Slow-wave dysrhythmias are thought to contribute to dysmotility syndromes such as postoperative gastroparesis, but the clinical significance of these dysrhythmias remains poorly defined. Electrogastrography (EGG) has been unable to characterize dsyrhythmic activity reliably, and the most accurate method for evaluating slow waves is to record directly from the surface of the target organ. This study presents a novel laparoscopic device for recording serosal slow-wave activity, together with its validation. METHODS: The novel device consists of a shaft (diameter, 4 mm; length, 300 mm) and a flexible connecting cable. It contains four individual electrodes and is fully shielded. Validation was performed by comparing slow-wave recordings from the laparoscopic device with those from a standard electrode platform in an open-abdomen porcine model. An intraoperative human trial of the device also was performed by recording activity from the gastric antrum of a patient undergoing a laparoscopic cholecystectomy. RESULTS: Slow-wave amplitudes were similar between the laparoscopic device and the standard recording platform (mean 0.38 ± 0.03 mV vs range 0.36-0.38 ± 0.03 mV) (p = 0.94). The signal-to-noise ratio (SNR) also was similar between the two types of electrodes (13.7 dB vs 12.6 dB). High-quality antral slow-wave recordings were achieved in the intraoperative human trial (amplitude, 0.41 ± 0.04 mV; SNR, 12.6 dB), and an activation map was constructed showing normal aboral slow-wave propagation at a velocity of 6.3 ± 0.9 mm/s. CONCLUSIONS: The novel laparoscopic device achieves high-quality serosal slow-wave recordings. It is easily deployable and atraumatic. It is anticipated that this device will aid in the clinical investigation of normal and dsyrhythmic slow-wave activity. In particular, it offers new potential for investigating the effect of surgical procedures on slow-wave activity.

Origin and propagation of the slow wave in the canine stomach: the outlines of a gastric conduction system.

Slow waves are known to originate orally in the stomach and to propagate toward the antrum, but the exact location of the pacemaker and the precise pattern of propagation have not yet been studied. Using assemblies of 240 extracellular electrodes, simultaneous recordings of electrical activity were made on the fundus, corpus, and antrum in open abdominal anesthetized dogs. The signals were analyzed off-line, pathways of slow wave propagation were reconstructed, and slow wave velocities and amplitudes were measured. The gastric pacemaker is located in the upper part of the fundus, along the greater curvature. Extracellularly recorded slow waves in the pacemaker area exhibited large amplitudes (1.8 +/- 1.0 mV) and rapid velocities (1.5 +/- 0.9 cm/s), whereas propagation in the remainder of the fundus and in the corpus was slow (0.5 +/- 0.2 cm/s) with low-amplitude waveforms (0.8 +/- 0.5 mV). In the antrum, slow wave propagation was fast (1.5 +/- 0.6 cm/s) with large amplitude deflections (2.0 +/- 1.3 mV). Two areas were identified where slow waves did not propagate, the first in the oral medial fundus and the second distal in the antrum. Finally, recordings from the entire ventral surface revealed the presence of three to five simultaneously propagating slow waves. High resolution mapping of the origin and propagation of the slow wave in the canine stomach revealed areas of high amplitude and rapid velocity, areas with fractionated low amplitude and low velocity, and areas with no propagation; all these components together constitute the elements of a gastric conduction system.

Gut peristalsis is governed by a multitude of cooperating mechanisms.

Peristaltic motor activity of the gut is an essential activity to sustain life. In each gut organ, a multitude of overlapping mechanisms has developed to acquire the ability of coordinated contractile activity under a variety of circumstances and in response to a variety of stimuli. The presence of several simultaneously operating control systems is a challenge for investigators who focus on the role of one particular control activity since it is often not possible to decipher which control systems are operating or dominant in a particular situation. A crucial advantage of multiple control systems is that gut motility control can withstand injury to one or more of its components. Our efforts to increase understanding of control mechanism are not helped by recent attempts to eliminate proven control systems such as interstitial cells of Cajal (ICC) as pacemaker cells, or intrinsic sensory neurons, nor does it help to view peristalsis as a simple reflex. This review focuses on the role of ICC as slow-wave pacemaker cells and places ICC into the context of other control mechanisms, including control systems intrinsic to smooth muscle cells. It also addresses some areas of controversy related to the origin and propagation of pacemaker activity. The urge to simplify may have its roots in the wish to see the gut as a consequence of a single perfect design experiment whereas in reality the control mechanisms of the gut are the messy result of adaptive changes over millions of years that have created complementary and overlapping control systems. All these systems together reliably perform the task of moving and mixing gut content to provide us with essential nutrients.

Focal activities and re-entrant propagations as mechanisms of gastric tachyarrhythmias.

BACKGROUND & AIMS: Gastric arrhythmias occur in humans and experimental animals either spontaneously or induced by drugs or diseases. However, there is no information regarding the origin or the propagation patterns of the slow waves that underlie such arrhythmias. METHODS: To elucidate this, simultaneous recordings were made on the antrum and the distal corpus during tachygastrias in open abdominal anesthetized dogs using a 240 extracellular electrode assembly. After the recordings, the signals were analyzed, and the origin and path of slow wave propagations were reconstructed. RESULTS: Several types of arrhythmias could be distinguished, including (1) premature slow waves (25% of the arrhythmias), (2) single aberrant slow waves (4%), (3) bursts (18%), (4) regular tachygastria (11%), and (5) irregular tachygastria (10%). During regular tachygastria, rapid, regular slow waves emerged from the distal antrum or the greater curvature, whereas, during irregular tachygastria, numerous variations occurred in the direction of propagation, conduction blocks, focal activity, and re-entry. In 12 cases, the arrhythmia was initiated in the recorded area. In each case, after a normal propagating slow wave, a local premature slow wave occurred in the antrum. These premature slow waves propagated in various directions, often describing a single or a double loop that re-entered several times, thereby initiating additional slow waves. CONCLUSIONS: Gastric arrhythmias resemble those in the heart and share many common features such as focal origin, re-entry, circular propagation, conduction blocks, and fibrillation-like behavior.

Mapping slow waves and spikes in chronically instrumented conscious dogs: automated on-line electrogram analysis.

Myoelectric recordings from the gastrointestinal (GI) tract in conscious animals have been limited in duration and site. Recently, we have implanted 24 electrodes and obtained electrograms from these sites simultaneously (200 Hz sampling rate; 1.1 MB/min data stream). An automated electrogram analysis was developed to process this large amount of data. Myoelectrical recordings from the GI tract often consist of slow wave deflections followed by one or more action potentials (=spike deflections) in the same traces. To analyze these signals, a first module separates the signal into one containing only slow waves and a second one containing only spikes. The timings of these waveforms were then detected, in real time, for all 24 electrograms, in a separate slow wave detection module and a separate spike-detection module. Basic statistics such as timing and amplitudes and the number of spikes per slow wave were performed and displayed on-line. In summary, with this online analysis, it is possible to study for long periods of time and under various experimental conditions major components of gastrointestinal motility.

Simulation and analysis of spatio-temporal maps of gastrointestinal motility.

BACKGROUND: Spatio-temporal (ST) maps provide a method for visualizing a temporally evolving and spatially varying field, which can also be used in the analysis of gastrointestinal motility. However, it is not always clear what the underlying contractions are that are represented in ST maps and whether some types of contractions are poorly represented or possibly not at all. METHODS: To analyze the translation from stationary or propagating rhythmic contractions of the intestine to ST maps, a simulation program was used to represent different patterns of intestinal contraction and to construct their corresponding ST maps. A number of different types of contractions were simulated and their ST maps analyzed. RESULTS: Circular strong contractions were well represented in ST maps as well as their frequency and velocity. Longitudinal contractions were not detected at all. Combinations of circular and longitudinal contractions were, to a limited extent detectable at a point in space and time. The method also enabled the construction of specific ST-patterns to mimic real-life ST maps and the analysis of the corresponding contraction patterns. CONCLUSION: Spatio-temporal simulations provide a method to understand, teach and analyze ST maps. This approach could be useful to determine characteristics of contractions under a variety of circumstances.

Origin and propagation of individual slow waves along the intact feline small intestine.

The pattern of propagation of slow waves in the small intestine is not clear. Specifically, it is not known whether propagation is determined by a single dominant ICC-MP (Interstitial cells of Cajal located in the Myenteric Plexus) pacemaker unit or whether there are multiple active pacemakers. To determine this pattern of propagation, waveforms were recorded simultaneously from 240 electrodes distributed along the whole length of the intact isolated feline small intestine. After the experiments, the propagation patterns of successive individual slow waves were analysed. In the intact small intestine, there was only a single slow wave pacemaker unit active, and this was located at or 6-10 cm from the pyloric junction. From this site, slow waves propagated in the aboral direction at gradually decreasing velocities. The majority of slow waves (73%) reached the ileocaecal junction while the remaining waves were blocked. Ligation of the intestine at one to four locations led to: (a) decrease in the distal frequencies; (b) disappearance of distal propagation blocks; (c) increase in velocities; (d) emergence of multiple and unstable pacemaker sites; and (e) propagation from these sites in the aboral and oral directions. In conclusion, in the quiescent feline small intestine a single pacemaker unit dominates the organ, with occasional propagation blocks of the slow waves, thereby producing the well-known frequency gradient.

Patterns of electrical propagation in the intact pregnant guinea pig uterus.

Previous studies have reported on propagation of individual spikes in isolated segments of the pregnant uterus, but there is no information on patterns of spike propagation in the intact organ. There is also no information on propagation of myometrial burst. The aim of this study was to record, at high resolution, patterns of propagation of electrical activities in the pregnant uterus. Sixteen timed-pregnant guinea pigs were euthanized at term, and their uteruses isolated. Fetuses were removed and replaced by an equal amount of Tyrode. A 240-electrode array was positioned at various locations along the organ, all signals were recorded simultaneously, and the electrical propagations were reconstructed. In the intact pregnant uterus at term, spikes propagated with high velocity in longitudinal (6.8 +/- 2.4 cm/s) and slower velocity in circular direction (2.8 +/- 1.0 cm/s; P < 0.01). Direction of propagation and frequency of activity were highly variable but showed similar patterns at the ovary or cervical end and along the anterior, posterior, and antimesometrial borders. Along mesometrium, spike propagation was sparse and fractionated. Migration of burst (0.6 +/- 0.4 cm/s) was significantly much slower than that of individual spikes (P < 0.001). Initial burst activity was located at variable locations along the ovarial end of the antimesometrial border, while the latest excitation occurred at the cervical end (1.2 +/- 0.9 min). In conclusion, high resolution electrical mapping of the intact pregnant uterus reveals fundamental properties in spatial and temporal patterns of spike and burst propagation that determine the contraction of the organ.