Normal and abnormal electrical propagation in the small intestine.

As in other muscular organs, small intestinal motility is determined to a large degree by the electrical activities that occur in the smooth muscle layers of the small intestine. In recent decades, the interstitial cells of Cajal, located in the myenteric plexus, have been shown to be responsible for the generation and propagation of the electrical impulse: the slow wave. It was also known that the slow waves as such do not cause contraction, but that the action potentials ('spikes') that are generated by the slow waves are responsible for the contractions. Recording from large number of extracellular electrodes simultaneously is one method to determine origin and pattern of propagation of these electrical signals. This review reports the characteristics of slow wave propagation through the intestinal tube, the occurrence of propagation blocks along its length, which explains the well-known decrease in frequency, and the specific propagation pattern of the spikes that follow the slow waves. But the value of high-resolution mapping is highest in discovering and analysing mechanisms of arrhythmias in the gut. Most recently, circus movements (also called 're-entries') have been described in the small intestine in several species. Moreover, several types of re-entries have now been described, some similar to what may occur in the heart, such as functional re-entries, but others more unique to the small intestine, such as circumferential re-entry. These findings seem to suggest the possibilities of hitherto unknown pathologies that may be present in the small intestine.

Arrhythmias in the gut.

In recent years, it has become possible to record, from a large number of extracellular electrodes, the electrical activities of smooth muscle organs. These recordings, after proper processing and analysis, may reveal origin and propagation of normal and abnormal electrical activities in these organs. Several publications have appeared in the past 5 years describing origin and propagation of slow waves in the stomach of experimental animals and in humans. Furthermore, publications are now starting to appear that describe pathophysiological patterns of propagation and these studies provide us with novel concepts regarding potential mechanisms of arrhythmias in the gut, crucial information if we are ever going to successfully treat patients suffering from such arrhythmias. In this issue of Neurogastroenterology & Motility, Angeli et al. have mapped the slow wave propagation in the porcine small intestine and discovered two types of reentry; functional reentry and circumferential reentry. Next to the descriptions of arrhythmias in the stomach, the fact that reentrant arrhythmias may also occur in the small intestine further extends this new emerging field of gastrointestinal (GI) arrhythmias. In this viewpoint, the relevance of these arrhythmias is further discussed and a few ideas for future research in this field, not necessarily constrained to the GI system, proposed.

Rapid high-amplitude circumferential slow wave propagation during normal gastric pacemaking and dysrhythmias.

BACKGROUND: Gastric slow waves propagate aborally as rings of excitation. Circumferential propagation does not normally occur, except at the pacemaker region. We hypothesized that (i) the unexplained high-velocity, high-amplitude activity associated with the pacemaker region is a consequence of circumferential propagation; (ii) rapid, high-amplitude circumferential propagation emerges during gastric dysrhythmias; (iii) the driving network conductance might switch between interstitial cells of Cajal myenteric plexus (ICC-MP) and circular interstitial cells of Cajal intramuscular (ICC-IM) during circumferential propagation; and (iv) extracellular amplitudes and velocities are correlated. METHODS: An experimental-theoretical study was performed. High-resolution gastric mapping was performed in pigs during normal activation, pacing, and dysrhythmia. Activation profiles, velocities, and amplitudes were quantified. ICC pathways were theoretically evaluated in a bidomain model. Extracellular potentials were modeled as a function of membrane potentials. KEY RESULTS: High-velocity, high-amplitude activation was only recorded in the pacemaker region when circumferential conduction occurred. Circumferential propagation accompanied dysrhythmia in 8/8 experiments was faster than longitudinal propagation (8.9 vs 6.9 mm s(-1) ; P = 0.004) and of higher amplitude (739 vs 528 µV; P = 0.007). Simulations predicted that ICC-MP could be the driving network during longitudinal propagation, whereas during ectopic pacemaking, ICC-IM could outpace and activate ICC-MP in the circumferential axis. Experimental and modeling data demonstrated a linear relationship between velocities and amplitudes (P < 0.001). CONCLUSIONS & INFERENCES: The high-velocity and high-amplitude profile of the normal pacemaker region is due to localized circumferential propagation. Rapid circumferential propagation also emerges during a range of gastric dysrhythmias, elevating extracellular amplitudes and organizing transverse wavefronts. One possible explanation for these findings is bidirectional coupling between ICC-MP and circular ICC-IM networks.

High-resolution spatial analysis of slow wave initiation and conduction in porcine gastric dysrhythmia.

BACKGROUND: The significance of gastric dysrhythmias remains uncertain. Progress requires a better understanding of dysrhythmic behaviors, including the slow wave patterns that accompany or promote them. The aim of this study was to use high-resolution spatiotemporal mapping to characterize and quantify the initiation and conduction of porcine gastric dysrhythmias. METHODS: High-resolution mapping was performed on healthy fasted weaner pigs under general anesthesia. Recordings were made from the gastric serosa using flexible arrays (160-192 electrodes; 7.6mm spacing). Dysrhythmias were observed to occur in 14 of 97 individual recordings (from 8 of 16 pigs), and these events were characterized, quantified and classified using isochronal mapping and animation. KEY RESULTS: All observed dysrhythmias originated in the corpus and fundus. The range of dysrhythmias included incomplete conduction block (n=3 pigs; 3.9±0.5cpm; normal range: 3.2±0.2cpm) complete conduction block (n=3; 3.7±0.4cpm), escape rhythm (n=5; 2.0±0.3cpm), competing ectopic pacemakers (n=5, 3.7±0.1cpm) and functional re-entry (n=3, 4.1±0.4cpm). Incomplete conduction block was observed to self-perpetuate due to retrograde propagation of wave fragments. Functional re-entry occurred in the corpus around a line of unidirectional block. 'Double potentials' were observed in electrograms at sites of re-entry and at wave collisions. CONCLUSIONS & INFERENCES: Intraoperative multi-electrode mapping of fasted weaner healthy pigs detected dysrhythmias in 15% of recordings (from 50% of animals), including patterns not previously reported. The techniques and findings described here offer new opportunities to understand the nature of human gastric dysrhythmias.

Origin, propagation and regional characteristics of porcine gastric slow wave activity determined by high-resolution mapping.

BACKGROUND: The pig is a popular model for gastric electrophysiology studies. However, its normal baseline gastric activity has not been well characterized. High-resolution (HR) mapping has recently enabled an accurate description of human and canine gastric slow wave activity, and was employed here to define porcine gastric slow wave activity. METHODS: Fasted pigs underwent HR mapping following anesthesia and laparotomy. Flexible printed-circuit-board arrays were used (160-192 electrodes; spacing 7.62 mm). Anterior and posterior surfaces were mapped simultaneously. Activation times, velocities, amplitudes and frequencies were calculated, and regional differences evaluated. KEY RESULTS: Mean slow wave frequency was 3.22 ± 0.23 cpm. Slow waves propagated isotropically from the pacemaker site (greater curvature, mid-fundus). Pacemaker activity was of higher velocity (13.3 ± 1.0 mm s(-1)) and greater amplitude (1.3 ± 0.2 mV) than distal fundal activity (9.0 ± 0.6 mm s(-1), 0.9 ± 0.1 mV; P < 0.05). Velocities and amplitudes were similar in the distal fundus, proximal corpus (8.4 ± 0.8 mm s(-1), 1.0 ± 0.1 mV), distal corpus (8.3 ± 0.8 mm s(-1), 0.9 ± 0.2 mV) and antrum (6.8 ± 0.6 mm s(-1), 1.1 ± 0.2 mV). Activity was continuous across the anterior and posterior gastric surfaces. CONCLUSIONS & INFERENCES: This study has quantified normal porcine gastric slow wave activity at HR during anesthesia and laparotomy. The pacemaker region was associated with high-amplitude, high-velocity slow wave activity compared to the activity in the rest of the stomach. The increase in distal antral slow wave velocity and amplitude previously described in canines and humans is not observed in the pig. Investigators should be aware of these inter-species differences.

Mapping slow waves and spikes in chronically instrumented conscious dogs: implantation techniques and recordings.

Myoelectric recordings from the intestines in conscious animals have been limited to a few electrode sites with relatively large inter-electrode distances. The aim of this project was to increase the number of recording sites to allow high-resolution reconstruction of the propagation of myoelectrical signals. Sets of six unipolar electrodes, positioned in a 3x2 array, were constructed. A silver ring close to each set served as the reference electrodes. Inter-electrode distances varied from 4 to 8 mm. Electrode sets, to a maximum of 4, were implanted in various configurations allowing recording from 24 sites simultaneously. Four sets of 6 electrodes each were implanted successfully in 11 female Beagles. Implantation sites evaluated were the upper small intestine (n=10), the lower small intestine (n=4) and the stomach (n=3). The implants remained functional for 7.2 months (median; range 1.4-27.3 months). Recorded signals showed slow waves at regular intervals and spike potentials. In addition, when the sets were positioned close together, it was possible to re-construct the propagation of individual slow waves, to determine their direction of propagation and to calculate their propagation velocity. No signs or symptoms of interference with normal GI-function were observed in the tested animals. With this approach, it is possible to implant 24 extracellular electrodes on the serosal surface of the intestines without interfering with its normal physiology. This approach makes it possible to study the electrical activities of the GI system at high resolution in vivo in the conscious animal.

Electrical activity in the rectum of anaesthetized dogs.

There is limited data available on the electrical activity of the rectum. An in vivo canine model was developed to record 240 extracellular electrograms simultaneously from the serosal surface of the rectum thereby enabling an off-line reconstruction of the behaviour of the electrical signals. Serosal rectal electrical activity is characterized by brief bursts of action potentials (=spikes) with a frequency of 22 cycles min(-1). High-resolution mapping of these signals revealed predominant propagation of these spikes in the longitudinal direction, originating from any site and conducted for a limited time and length before stopping spontaneously, thereby describing a patch of activity. The dimension of the patches in the longitudinal direction was significantly longer than the transversal width (13.6 vs 2.4 mm; P < 0.001). Spike propagation could occur in the aboral (46% of cases), in the oral (34%) or in both directions (20%). A bolus of betanechol (i.v., 0.5 mg kg(-1)) increased the frequency of the spikes without affecting size, shape or orientation of the patches. As in other parts of the gastrointestinal system, individual spike propagation in the rectum is limited to small areas or patches. The contractile activity of the organ could possibly reflect this underlying pattern of electrical behaviour.

Spatiotemporal electrical and motility mapping of distension-induced propagating oscillations in the murine small intestine.

Since the development of knockout animals, the mouse has become an important model to study gastrointestinal motility. However, little information is available on the electrical and contractile activities induced by distension in the murine small intestine. Spatiotemporal electrical mapping and mechanical recordings were made from isolated intestinal segments from different regions of the murine small intestine during distension. The electrical activity was recorded with 16 extracellular electrodes while motility was assessed simultaneously by tracking the border movements with a digital camera. Distension induced propagating oscillatory contractions in isolated intestinal segments. These propagating contractions were dictated by the underlying propagating slow wave with superimposed spikes. The frequencies, velocities, and direction of the propagating oscillations strongly correlated with the frequencies (r = 0.86), velocities (r = 0.84), and direction (r = 1) of the electrical slow waves. N(omega)-nitro-L-arginine methyl ester decreased the maximal diameter of the segment and reduced the peak contraction amplitude of the propagating oscillatory contractions, whereas atropine and verapamil blocked the propagating oscillations. Tetrodotoxin had little effect on the maximal diameter and peak contraction amplitude. In conclusion, distension in the murine small intestine does not initiate peristaltic reflexes but induces a propagating oscillatory motor pattern that is determined by propagating slow waves with superimposed spikes. These spikes are cholinergic and calcium dependent.

Spatial determination of successive spikes in the isolated cat duodenum.

In seven isolated segments of the feline duodenum, the timings of all spikes and the locations of all spike patches that occurred after 12-16 successive slow waves were analysed. Simultaneous recordings were performed during 1-min periods using 240 extracellular electrodes (24 x 10 array; interelectrode distance 2 mm) positioned onto the serosal surface. In all seven preparations, spikes always occurred during the first half of the slow wave cycle. From preparation to preparation, and within 1-min periods in each preparation, there was limited variation in the spike-spike intervals, in the times between the spikes and the preceding slow wave and in the number of spikes at each electrode site. In contrast, the number of electrode sites that recorded spikes and the number of spike patches both showed great variability between preparations and sometimes within a single preparation. In addition, the location of spikes and spike patches was not random but was significantly concentrated in certain areas, often located along the anti-mesenteric border, while other sites showed little or no spike activity. In conclusion, spikes and spike patches tend to occur significantly in some areas and not in others. This spatial heterogeneity will play a role in intestinal motility.

Anisotropic propagation in the small intestine.

Abstract Measuring propagation anisotropy may help in determining the tissue layers involved in the propagation of electrical impulses in the intestine. We used 240 extracellular electrograms recorded from the isolated feline duodenum. The conduction velocities of slow waves and of individual spikes were measured from their site of origin into all directions. Both slow waves and spikes propagate anisotropically in the small intestine but in different directions and to a different degree. Slow waves propagated anisotropically faster in the circumferential (1.7 +/- 0.8 cm s(-1)) than in the axial direction (1.3 +/- 0.5 cm s(-1); P < 0.001). Spikes, on the other hand, propagated faster in the longitudinal direction (7.8 +/- 4.5 cm s(-1)) than in the circumferential direction (3.3 +/- 4.3 cm s(-1); P < 0.001). Furthermore, the average conduction velocity of spikes (6.3 +/- 4.5 cm s(-1)) was significantly higher than that of slow waves (1.5 +/- 1.1 cm s(-1); P < 0.001). The anisotropic propagation of spikes supports the argument that these propagate in the longitudinal muscle layer. The anisotropic propagation of slow waves may be the result of the interaction between the myenteric layer of interstitial cells of Cajal and their electrotonic connection to both the longitudinal and the circular muscle layer.