Migrating Electrical Spike Activity in the Fasting Human Small Intestine PETER F L E C K E N S T E I N , MD

The purpose of the present investigation was to describe characteristics of migrating electrical phenomena in the human small intestine. A specially designed probe with several bipolar electrodes was placed in the upper small intestine of 5 normal, fasting volunteers for continuous registration of electrical spike potentials. A migrating myoelectric complex was observed resembling observations made previously in animal experiments. The active phase consisted o f regular spike potentials propagating distally at a mean velocity o f 12 cm/min, and a duration o f about 5 min. In addition a "peristaltic rush" was observed consisting of spike potentials with a high amplitude, propagating distally at a mean velocity of 2 cm/sec and a duration o f about 5 sec.

The interdigestive myoelectric complex was first demonstrated by Szurszewski and Code (1) and Szurszewski (2) from experiments with implanted electrodes in the small intestine of fasting dogs. Since then, a number of reports have described a recurring fasting activity in various animals, with an active phase of regular spike potentials which originate in the distal part of the stomach and propagate distally through the entire length of the small intestine (3-6). When an active phase has reached the ileocoecal junction, another originates in the stomach. The propagation velocity of the active phase has been shown to be about 1-10 cm/min. In dogs this phase has a duration of about 5-10 min and is part of an activity cycle, which can be divided into 3 or 4 phases. A n o t h e r type of migrating activity has been described by some authors, consisting of a rapidly progressive wave of short duration which has been termed " t h e peristaltic r u s h " (7, 8). In the present

From the Department of Diagnostic Radiology, Rigshospitalet, University of Copenhagen, Blegdamsvej, DK 2100 Denmark. This study was supported by Danish Research Council and grants from Frk. P.A. Brandt's Legacy. Address for reprint requests: Dr. Peter Fleckenstein, Department of Diagnostic Radiology, Rigshospitalet, DK 2100 Copenhagen, Denmark.

investigation the above-mentioned motility patterns are described from recordings in the upper small intestine of fasting humans. MATERIALS AND METHODS Five healthy young volunteers were studied after a fasting period of 24 hr. Water was allowed until 18 hr before the examination. The probe consisted of a polyethylene tube, size 18 French gage, 225 cm long, containing an inner radiopaque polyethylene catheter (inner diameter 1.7 mm, outer diameter 2.6 mm), which was used for the introduction of a guide wire and shielded fine copper wires (diameter 0.13 mm). Bipolar electrodes were formed from the distal end of the wires which were unshielded and had been wound twice around the outer tube. Eleven pairs of electrodes with an interelectrode distance of 5 mm were placed at intervals of 10 cm. The tube was introduced transnasally and advanced as far as possible, so that 5-11 electrodes were distal to the pylorus. This implied recordings from a segment of 50110 cm of the upper small intestine. Recording was not obtained from the electrodes proximal to the pylorus. The position was controlled by fluoroscopy. Each pair of electrodes was connected to a 8-channel curve writer (EEG mingograph Elema-Sch6nander). The upper frequency limit was 700 Hz, and the electrical time constant was 0.015 sec. The paper speed was 3 mrrgsec. Total observation time was 23 hr 25 min, ranging from 3 hr 30 min to 6 hr 40 min. Record Analysis. Spike potentials were defined as a series of rapid positive and negative deflections forming a

Digestive Diseases, Vol. 23, No. 9 (September 1978)

0002-9211/78/0900-0769505.00/19 1978DigestiveDisease Systems Inc.

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FLECKENSTEIN well-defined burst. Three phases could be identified from the recordings (Figure 1) and were defined as follows: phase I, no or occasional isolated bursts of spike potentials; phase II, irregular spike potentials with at least 2 bursts of spike potentials/100 sec during 300 sec (5 min); phase III (active phase); spike potentials occurring in a regular rhythm during more than 100 sec. The total duration of a migrating myoelectric complex (i.e., phase I + II + III) was defined as the time interval between onset of two consecutive phase III periods at one point of observation. The following measurements and calculation were madei 1. Duration of the individual myoelectric complex. 2. Duration of the individual phases within a complex. Details regarding phase III were analyzed in the following way: 3. Duration in relation to the distance from the pylorus (Figure 2). 4. Time of onset of the individual phase III in relation to their distance from pylorus (Figure 4). 5. Propagation velocity (cm/min) of each active phase based on time of appearance at the three most proximal electrodes (duodenum) and the three most distal electrodes (jejunum) (Figure 4, V1 and V2). 6. The segment of the small intestine which was simultaneously activated was measured directly as ap: pears from Figure 4 (11 and 12) in the duodenum and the jejunum. 7. Peak-peak amplitude and duration of 10 consecutive spike potentials from the beginning, middle, and end of the active phase in all tracings. 8. Number of bursts of spike potentials/100 sec in all tracings. In the present investigation "the peristaltic rush" was defined as a fast migrating wave of activity of short duration propagating over at least 30 cm of the small intestine. The following calculations were made regarding "the peristaltic rush": 1. Distance of propagation. 2. Propagation velocity (cm/sec) expressed as mean values for the entire distance observed. When the rush was observed over a distance of more than 40 cm additional calculations or propagation velocity during the most proximal and the most distal 20 crn were made. 3. Peak-peak amplitude and duration in all tracings. 4. The extent of the section of gut activated simultaneously calculated by multiplying the mean duration with the mean propagation velocity for each rush.

RESULTS Two different types of migrating electrical activity were observed in all subjects examined: an active phase (phase III) of regular electrical spike potentials which had a comparatively long duration (min) and propagated distally at a comparatively slow rate (cm/min), and a fast rush of activity with a short

770

duration (sec) which propagated at a high speed (cm/sec).

Migrating Complex of Regular Electrical Spike Potentials. After prolonged fasting irregular spike activity was observed during most of the time (phase II). After a period of increasing Spike activity, there was an abrupt onset of regular spike potentials in the duodenum (phase III) subsequently appearing in all the recordings. As indicated in Figure la, the spike potentials appeared to be phase-locked during regular activity. The rhythmic activity terminated as abruptly as it had started and was followed by a period with no spike potentials (phase I). In each of the examined persons at least two such complexes were seen. A total of 14 phase-Ill periods were observed. Two active phases could only be recorded from t h e d i s t a l electrodes and the recording of 4 of the active phases was technically insufficient. The remaining 8, which were well-defined in all tracings, were analyzed in detail. All phase-III periods had a similar appearance (Figure 1). The total duration of myoelectric complexes was 158, 145, i72, 147, and 122 min, with no significant difference in the various leads. The period with no spike activity (phase I) varied between 20 and 90 min, and the Period with r a n d o m l y o c c u r r i n g b u r s t s o f spike p o t e n t i a l s (phase II) was 35-135 rain. The duration of phase III at one recording position ranged between 145 and 680 sec (mean, 301 sec). The duration tended to increase with increasing distance from the pylorus (Figure 2) (KruskalWallis one-way analysis of variance P < 0.05). Figure 3 demonstrates the relation between onset of phase III and distance from the pyloms. The slope at a given point represents the propagation velocity of the front of the ~active phase. As demonstrated, the velocity is relatively constant o v e r the most proximal 30 cm. Distal to this point, the curves flatten out corresponding to a decrease in velocity. The mean velocity was i2 cm/min inthe duodenum (proximal three recordings) and 6 cm/min in the upper jejunum (distal three recordings). ' This difference was statistically significant (paired rank sum test P < 0.01). The mean length of the gut which was activated simultaneously was 41 cm proximally (range 21-48 cm) and 29 cm distally (range 20-36 cm) (Figure 4 h and lz). This difference was also statistically significant (paired rank sum test P < 0.05). The calculated extent based on propagation velocity multiplied by the duration was essentially the same (P < 0.01). Digestive Diseases, Vol. 23, No. 9 (September 1978)

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Fig 1. E l e c t r o m y o g r a m from the small intestine in man. Recordings from bipolar electrodes at various distances from pylorus (vertical axis), a - d represent c o n s e c u t i v e recordings of regular spike activity (phase III). In (a) an initial peristaltic rush is shown. Solid lines connecting the beginning of spike potentials at multiple sites indicate increase in p h a s e lag at i n c r e a s i n g d i s t a n c e f r o m t h e p y l o r u s . V e r t i c a l b a r s = 150/xV. TC = 0.015 sec. Paper speed 3 m m / s e c .

As it appears from Figure 1, there was a change in amplitude of spike potentials during the recording. Thus the peak-peak amplitude was significantly higher in the middle part of phase III (mean 0.18 mV, SD +-- 0.04), compared to the beginning (mean, 0.13 mV) and the end (mean, 0.8 mV) (paired rank sum test P < 0.01). Spike potentials from the beginning of the active period had a significantly higher amplitude than those from the end of the period (P < 0.05). The duration of spike potentials from Digestive Diseases, Vol. 23, No. 9 (September 1978)

the middle part of the active period (mean 3.1 sec, SD -----0.8) was also greater than that of potentials from the beginning (mean, 1.7 sec) and the end (mean, 1.4 sec) of the active period (paired rank sum test P < 0.01). Likewise potentials from the beginning had a greater duration than those from the end of phase III (P < 0.05). Since no systematic tendency was found between recordings from different levels of the small bowel, the above-mentioned calculations were based on mean values for

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In 3 of the 8 phase-III periods analyzed, the rush was observed as an initial part as illustrated in Figure 5. An initial peristaltic rush is also shown in Figure la. The rushes were observed propagating over distances of up to 80 cm. The mean velocity for the entire distance of p r o p a g a t i o n was 2.1 cm/sec (SD --+ 0.7), and the propagation velocity was significantly higher in the most proximal 20 cm compared to the most distal 20 cm (paired rank sum test P < 0.05 (Figure la). The velocity did not vary from one s u b j e c t to another (varians analysis P < 0.05). The spike potentials forming the rush had a mean amplitude of 0.33 mV (st> ___0.13) and a mean duration of 5.0 sec (SD -----1.6). The amplitude was significantly higher than the mean amplitude of spike potentials during phase III ( M a n n - W h i t n e y test P < 0.01). The calculated length of the section of gut activated simultaneously during a peristaltic rush was 10.5 cm (mean, SD _-2 3.4).

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groups of spike potentials from all levels of recording. The frequency of spike potentials showed a decreasing tendency with increasing distance from the pylorus. Thus the frequency was 20/100 sec (12/ min) median value at the gastroduodenal junction. Ten cm distal to this point it was 19/100 sec; 20-50 cm distal, 18/100 sec; and 60-90 cm distal to the gastroduodenal junction, the frequency was 17/100 sec. One hundred cm distal to the pylorus the frequency was 16/100 sec (9.6/min). The change in frequency of spike potentials from the most proximal to the most distal tracing was statistically significant (Wilcoxon test for pair differences P < 0.05). "Peristaltic Rush." In all subjects isolated spike potentials of high amplitude and short duration could be observed consecutively in an aborad direction through the various leads (Figure 5). A total of 23 rushes were observed initiating on a level with the pylorus. The peristaltic rush was not seen during phase I, but appeared at random during phase II.

DISCUSSION In canine studies, Szurszewski and Code (1) and Szurszewski (2) demonstrated a complex of regular rhythmic spike potentials progressing slowly through the entire length of the small intestine. When this activity complex reached the ileocoecal junction, another appeared in the duodenum. Other animal experiments have shown that the complex originates simultaneously in the stomach and the duodenum (6). The complex has been identified by several workers as part of an activity cycle in the small intestine, which is repeated at regular intervals (3-5, 9-11). In the above-mentioned work by Code and Marlett, this activity cycle was divided into four phases: phase I without spike activity,

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Digestive Diseases, Vol. 23, No. 9 (September 1978)

MIGRATING ACTIVITY IN HUMAN INTESTINE phase II with persistent but irregular activity, and phase III corresponding to the "electric complex" described by Szurszewski (2). During phase III the spike potentials occurred at a regular rhythm with a frequency corresponding to the slow waves (BER), and all of them had a large amplitude. Phase III terminated abruptly and was followed by phase IV, with a rapid decrease in incidence and intensity of spike potentials. Phase IV was only found occasionally and has not been observed by all authors (4, 5). The mean duration of the migrating myoelectric complex has been similar in all canine studies, varying between 80 and 110 min (3-6). In the present investigation, the migrating myoelectric complex is described in human beings. The characteristics of the individual phases correspond closely to the ones described in the above-mentioned canine studies. The duration of one activity cycle was somewhat longer than the corresponding value from dog experiments. The duration of phase I and II was rather variable, but both were in the same order of lengths as in the animal studies. Comparable results have been reported recently by Vantrappen et al (12) from pressure studies in humans. The duration of phase III has been found similar in all the reports. Szurszewski (2) found a duration in the duodenum of about 6 min. He, as well as Carlson et al (3) and Grivel and Ruckebusch (4), had somewhat variable values at various distances from the pylorus, but with no definite tendency. Conversely, Code and Marlett (6) found a decreasing duration of phase III, with increasing distance from the pylorus. In the present investigation the duration of phase III was about 5 min in the upper

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d ' 2b0 ' hb0 ' 660 ' ~bo' 10'00,ec Fig 4. S c h e m a t i c diagram of the appearance of one phase-III activity (same as in Figure 2). Zero time represents time of o n s e t of p h a s e III in the m o s t proximal tracing (10 cm from the pylotus). V~ and V2 indicate propagation velocity o f the front of p h a s e III; i1 and 12 r e p r e s e n t sections o f the intestine activated at one time. Note the difference in inclination b e t w e e n V1 and V2 and the difference b e t w e e n 11 and 12. Digestive Diseases, VoL 23, No. 9 (September 1978)

part of the human small intestine, and contrary to the above-mentioned animal experiments, this duration increased significantly with increasing distance from the pylorus. This discrepancy may be explained by difference in species. However, the distance between electrodes used in most animal experiments appears to be too great for differentiated calculations. Recently, Code and Marlett (6) have compared the propagation velocity from three different dog experiments. All these authors found the mean propagation velocity to be greatest at the pyloric level (5-12 crrgmin) with a decreasing tendency towards the middle part of the small intestine (2-4 cm/ rain). The velocity in the distal part of the small intestine appeared to be slightly decreasing or unchanged. In all the animal experiments mentioned above, the distance between implanted electrodes appears to have been assessed with some uncertainty. This can obviously also influence on the calculated values for propagation velocity and the extent of the activated section of bowel. In the present investigation, determination of the propagation velocity of phase III has been based upon the front of the complex and, similar to animal experiments, this velocity showed a significant decrease from the duodenum to the jejunum (12 cm/ rain to 6 crn/min). The extent of the section of the gut which is activated at one time (ie, regular spike activity) has been determined from animal experiments by multiplying the calculated velocity with the duration of phase III at one given moment of observation. In the duodenum the results of Szurszewski (2) and Code and Marlett (6) indicate mean values of about 30 and 50 cm, respectively. Our results indicate that in humans the extent of the activated bowel section is 35 cm, on a level with the duodenum, while in the jejunum the same value was 25 cm. There was a close correlation between calculated values and direct measurements on the curves. The observed changes in propagation velocity and extent of active bowel section indicate that the decrease in propagation velocity is relatively larger than the increase in duration. In animal experiments the recorded spike potentials during the entire phase III have a uniform maximal amplitude and duration. In the human recordings presented here, there was a change in the amplitude and duration of the potentials during phase III, which was similar in all tracings. At any point of observation there was a gradual increase in ampli-

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tude and duration of the potentials up to a certain maximum, after which there was a gradual decrease to values somewhat below the initial ones. It appears from Figure 1 that the spike potentials during phase III occur at a regular rhythm, and it also appears from the figure that the potentials are phase-locked. Since each slow wave (BER) is k n o w n to be associated with one spike potential during maximal regular activity (13), the frequency of spike potentials may in this case be used as a measure of slow-wave frequency. The frequency of BER has been shown to decrease with increasing distance from the pylorus (14). This is in accordance with results presented above, since there was a decreasing frequency of regular spike potentials during phase III from the duodenum (12 spike potentials/min) to the jejunum (9.6 spike potentials/ min). In dogs phase III is only present in the fasting state, but in other animals it has also been demonstrated after feeding (4, 9, 11). Code called phase III "the housekeeper" of the small intestine, because emptying of the bowel could be demonstrated by cinefluoroscopy during this type of activity (15). Some authors have shown a close relation between phase III and bowel transit (5, 10, 16). The activity can be modified by hormonal and neural influences (9, 17, 18) and several authors have demonstrated a disruption of the various phases of the activity cyclus of the small intestine during feeding (5, 6, 10, 11, 16-18).

774

The "peristaltic rush" is a swift wave of activity in the small intestine which progresses distally at a relatively fast rate. Only very sparse reports can be found in the literature (7, 8). Formerly, physiologists observed a progressing peristaltic wave (Rollbewegung) by inspecting the small bowel directly (19, 20). The electrical counterpart of this phenomenon has recently been demonstrated (4, 11, 21). A so-called "real housekeeper" has been described by Code and Schlegel (14) from cinefluorographic studies in the dog. These authors observed consecutive peristaltic waves migrating distally at a rate corresponding to the propagation velocity of the pacesetter potentials. The phenomenon occurred during phase III. In the a b o v e - m e n t i o n e d work by Grivel and Ruckebusch (4), 3 or 4 spike potentials propagated distally between two electrodes and accompanied a great pressure wave together with an expulsion of large volumes of intestinal contents. Like Code and Schlegel (14), these authors also found propagation velocity on the order of magnitude of the pacesetter potentials. In the present investigation, a similar phenomenon has been demonstrated in human beings. It was observed at random during phase II of the activity cycle. In some instances it could also be observed as an initial part of phase III. The potentials observed on the curves may partly be due to mechanical artifacts. However, there can be no doubt that Digestive Diseases, Vol. 23, No. 9 (September 1978)

M I G R A T I N G A C T I V I T Y IN H U M A N

INTESTINE

they represent a propagating wave of activity. This is further stressed by the following facts: (1) The potentials appear consecutively in the various tracings. (2) The appearance of the potentials is uniform in various tracings as well as in different subjects. (3) Propagation velocity of the rush is uniform and all the rushes observed had the same velocity, Which correspond to the velocity found in the animal studies (see above). (4) The propagation velocity of the rush corresponds to the propagation velocity of the pacesetter potentials as observed from animal experiments (22, 23). The present investigation only deals with the electrical activity in the duodenum and upper jejunum. Further studies will deal with the activity along the entire small intestine during longer periods of observation. The pattern of activity after feeding also calls for further investigation, and the physiological significance of the myoelectric complex and the peristaltic rushin relation to the transport mechanism must be evaluated in normal subjects as well as in patients with gastrointestinal disorders. REFERENCES 1. Szurszewski JH, Code CF: Activity fronts of the canine small intestine (abstract). Gastroenterology 54:1304, 1968 2. Szurszewski JH: A migrating electric complex of the canine small intestine. Am J Physiol 217:1757-1763, 1969 3. Carlson GM, Bedi BS, Code CF: Mechanism of propagation of intestinal interdigestive myoelectric complex. Am J Physio! 222!1027-1030, 1972 4. Grivel M-L, Ruckebusch Y: The propagation of segmental contractions along the small intestine. J Physiol 227:611625, 1972 5. Bueno L, Fioramonti J, Ruckebusch Y: Rate of flow of digesta and electrical activity of the small intestine in dogs and sheep. J Physiol 249:6%85, 1975 6. Code CF, Marlett JA: The interdigestive myo-electric complex of the stomach and small bowel of dogs. J Physiol 246:289-309, 1975 7. Hightower NC: Motor action of the small bowel. Handbook of Physiology, Section 6: Alimentary Canal, Vol. IV. CF Code, W Heidel (eds). Washington, D.C., American Physiological society, 1968, pp 2001-2024

Digestive Diseases, Vol. 23, No. 9 (September 1978)

8. Code CF, Szurszewski JH, Kelly KA, Smith IB: A concept of control of gastrointestinal motility. Handbook of Physiology, Section 6: Alimentary Canal, Vol. V. CF Code, W Heidel (eds). Washington~ D.C., American Physiological Society, 1968, pp 2881-2896 9. Ruckebusch Y, Bueno L: Electrical activity of the ovine jejunum and changes due to disturbances. Am J Dig Dis 20:1027-1034, 1975 10. Ruckebusch M, Fioramonti J: Electrical spiking activity and propulsion in small intestine in fed and fasted rat. Gastroenterology 68:1500-1508, 1975 11. Ruckebusch Y, Bueno L: The effect of feeding on the motility of the stomach and small intestine in the pig. Br J Nutr 35:397-405, 1976 12. Vantrappen G, Janssens J, Hellemans J, Ghoos Y: The interdigestive myoelectric complex in normal subjects and patients with bacterial overgrowth in the jejunum. Gastroenterology 72:1167, 1977 13. Bass P, Code CF, Lambert EH: Motor and electric activity of the duodenum. Am J Physiol 201:287-291 , 1961 14. Christensen J, Schedl HP, Clifton JA: The small intestinal basic electrica! rhythm (slow wave) freqUency gradient in normal men and in patients with a variety of diseases. Gastroenterology 50:309-315, 1966 15. Code CF, Schlegel JF: The gastrointestinal interdigestive housekeeper: Motor correlates of the interdigestive myoelectric complex of the dog. Proc Fourth Int Syrup on Gastrointestinal Motility, EE Daniel (ed). Vancouver, MithCell Press Ltd, 1974, pp 631-634 16. Summers RW, Helm J, Christensen J: Intestinal propulsion in the dog. Its relation to food intake and the migratory myoelectric complex. Gastroenterology 70:753-758, 1976 17. Weisbrodt NW, Copeland EM, Kearlet RW, Moore EP, Johnson LR: Effects of pentagastrin on electrical activity df small intestine of the dog. Am J Physiol 227:425-429, 1974 18. Marik F, Code CF: Control of the interdigestive myoelectric activity in dogs by the vagus nerves an d pentagastrin. Gastroenterology 69:387-395, !975 19. Engelmann Th W: Ueber die peristaltische Bewegung, insbesondere des Darms. Arch Gesammte Physiol 4:33-50, 1871 20. Meltzer SJ, Auer J: Peristaltic rush. Am J Physiol. 20:259281, 1907 21. Ruckebush Y, Bueno L: The effect of weaning on the motility of the small intestine in the calf. Br J Nutr 30:491-499, 1973 22. Armstrong HIO, Milton GW, Smith AWH: Electropotentiat changes of the small intestine. J Physiol 131:147-153, 1956 23. Weisbrodt NW, Christensen J: Electrical activity of the cat duodenum in fasting and vomitting. Gastroenterology 63:1004-1010, 1972

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