Study of Electromechanical Activity of the Stomach in Humans and in Dogs With Particular Attention to tachygastria

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1 GASTROENTEROLOGY 1984;86: Study of Electromechanical Activity of the Stomach in Humans and in Dogs With Particular Attention to tachygastria CHUL H. YOU and WILLIAM Y. CHEY The Isaac Gordon Center for Digestive Diseases and Nutrition, Department of Medicine, The Genessee Hospital, and University of Rochester School of Medicine and Dentistry, Rochester, New York The relationship between electric and mechanical activities of the gastric antrum was investigated in both humans and dogs. In 2 patients, in whom platinum monopolar electrodes were implanted on the serosal surface of the antrum and a perfused manometric tube was placed in the stomach, the number of gastric contractions detected by manometry was only <50% of the pacesetter potentials accompanied by action potentials or second potentials. No contraction of the stomach was recorded by manometry when pacesetter potentials occurred without action potentials or second potentials. The relationship was further investigated in 11 anesthetized dogs prepared with implanted electrodes and sensitive ministrain gauges implanted on the serosal surface of the stomach and an intragastric manometric tube. In these dogs, phasic contractions were always recorded by the method using ministrain gauges although the electrical activity showed only PSPs without action potentials or second potentials. The manometry, however, could not recognize these phasic contractions. When the stomach was stimulated by bethanechol infusion through the splenic artery, as in the human stomach, the manometry detected <50% of gastric contractions detected by the strain gauge recording. The gastric dysrhythmia including tachygastria, tachyarrhythmia, and bradygastria was induced in 10 dogs by epinephrine, 100 JLg' kg-i. h-l, infused via the splenic artery. Received August 5, Accepted December 21, Address requests for reprints to: Chul H. You, M.D., The Genesee Hospital, 224 Alexander Street, G.!. UnitlWW5, Rochester, New York This work was supported by The Genesee Hospital Gastrointestinal Research Fund. The authors thank Ms. Amy Winterberger for her technical assistance and Ms. Diane DeMent for the preparation of the manuscript by the American Gastroenterological Association /84/$3.00 During the period of gastric dysrhythmia, the phasic contractions disappeared and no contraction associated with action potential could be observed. The phasic contractions reappeared as long as the PSPs occurred regularly in a frequency of 4-5 cycles/min during either the control period or during the period of epinephrine infusion. The epinephrine-induced gastric dysrhythmia was blocked or reversed to normal pacesetter potentials by intraarterial infusion of phentolamine. Our study suggests the following: (1) the pacesetter potentials not only pace and direct gastric contraction, but they may also playa role in the genesis of phasic contractions of the stomach, and (2) gastric contractions detected by sensitive strain gauges are not always recorded by the intraluminal manometry and, thus, gastric dysrhythmia may not be detected by the manometry in humans. Although myoelectric activity of the gastrointestinal smooth muscle has been recognized since 1922 (1), it has not been well clarified whether or not a slow wave (pacesetter potential, PSP) per se is associated with a mechanical contraction. However, a prevailing view in this field has been that gastric contractions result from the occurrence of spike activity (action potential) and not from that of slow wave alone (2-5). Garrett (2) illustrated this relationship best in the simultaneous recording of electrical and mechanical activity of the gastric antrum of a healthy human. Thus, the function of slow wave was defined as setting the pace and direction of gastric contractions. Papasovaand Boev (6), on the other hand, reported that there was an intimate relationship between the contractile activity and PSP in the canine stomach, whether PSP was accompanied by Abbreviations used in this paper: ME, myoelectric activity; PSPs, pacesetter potentials.

2 June 1984 ELECTROMECHANICAL ACTIVITY OF THE STOMACH 1461 III ELECTRODES ~ MANOMETRIC TUBE ~ WITH OPENINGS Figure 1. Schematic drawing of the positions of implanted serosal electrodes and intraluminal manometric tube. E and M represent electrodes and manometry, respectively. The subnumber indicates the recording sites. an action potential (spike activity) or not. A similar relationship between a contraction and a PSP was found in human antral muscle segments (7) as well as canine antral longitudinal muscle strips (8). The latter observations (6-8), thus, strongly suggest that the PSP in the stomach may not only set the pace and direction of gastric contraction but also promote phasic contraction. When a force of mechanical contractions of stomach muscle is not strong enough to influence an intragastric pressure, a conventional intraluminal pressure recording method may not recognize such a force. Alternatively, depending on the sensitivity of the intraluminal recording system one uses, the results of gastric manometry may vary significantly from one system to another. Detection of the tachygastria and tachyarrhythmia that occur in both dogs (9) and humans (10-13) has been possible by myoelectric recording of the gastric antrum. It has not been known, however, whether or not tachygastria, tachyarrhythmia, or bradygastria (13) can be detected by a more readily available method such as a gastric manometry than by a recording system using strain gauges or electrodes. Patients with a myoelectric abnormality of the stomach were found to have a symptom complex of upper abdominal bloating, unexplained nausea or vomiting, or both (11,12,14), and delayed gastric emptying (10,14). The purpose of the present study was to determine the relationship between gastric myoelectric activity and mechanical contraction recorded by a simultaneous recording system. The recording systems in- clude sensitive ministrain gauges, an intraluminal pressure recording system, and implanted electrodes in dogs during a control period without a pharmacologic agent and periods of drug-induced gastric dysrhythmia. We also studied two human subjects in whom simultaneous recording of both myoelectric activity and intraluminal pressure changes could be performed. Materials and Methods Studies in Humans Two patients with unexplained nausea or vomiting, or both, early satiety, abdominal bloating and pain, and weight loss were studied using implanted platinum monopolar electrodes by the method described previously (11). The informed written consents were obtained after explanation of possible risks and benefits. The research protocol was approved by the Human Use Committee of The Genesee Hospital. After an overnight fast, the 2 patients swallowed a four-lumen manometric tube (OD 6 mm), which had four recording sites spaced 5 cm apart. Small metal pieces were attached immediately distal to the recording sites for fluoroscopic identification. After an overnight fast, a four-lumen polyvinyl tube was passed orally to position the three openings in the stomach with the most distal one in the proximal duodenum. The opening of the recording lumen immediately proximal to the latter recording site was placed in the distal antrum, 2 cm proximal to the pylorus and, thus, the two remaining proximal recording sites were located 7 and 12 cm proximal to the pylorus. The manometric recording sites and the sites of implanted electrodes on the serosal surface of the stomach were approximately in the same region (Figure 1). Each manometric tube was perfused with sterile water at a rate of 0.6 mllmin by a pneumohydraulic perfusion system (Arndolfer Medical Specialities, Green- [ij m ~ ELECTRODES STRAIN GAGES MANOMETRIC TUBE WITH OPENINGS Figure 2. Schematic drawing of the positions of implanted serosal electrodes, strain gauges, and intraluminal manometric tube. E, S, and M represent electrode, strain gauge, and manometry. The subnumber indicates the recording sites.

3 1462 YOU AND CHEY GASTROENTEROLOGY Vol. 86, No. 6 I, :'I. -J. ''"'<..r-~~ ~- /-... J ;-'li"i, ~ 'r, mv Figure 3. Simultaneous recording of myoelectric activity (E) and intraluminal pressure changes (M) at the different areas of the human stomach after subcutaneous injection of bethanechol. E, is at the proximal antrum, E2 the midantrum, and E3 the distal antrum. dale, Wis.). Pressure was recorded by a quartz transducer (Hewlett-Packard Company, Waltham, Mass.) and connected via amplifier to a chart recorder (Hewlett-Packard Company). In order to stimulate motility, bethanechol was administered subcutaneously in a dose of 2.5 mg. Studies in Dogs Eleven mongrel dogs weighing between 15 and 20 kg were studied. The dogs were anesthetized by Lv. injection of pentobarbital. Respiration was facilitated with an endotracheal tube, and a respirator was used when necessary. After exposing the stomach via a midline incision on the abdomen, three monopolar electrodes and three strain gauges were sutured on the serosal surface of the antral wall of the stomach perpendicular to its longitidinal axis near its greater curvature. The strain gauges were constructed by the method described by Bass and Wiley (15) and were connected via strain gauge coupler to the chart recorder (Glass Company, Quincy, Mass.). The electrodes were positioned at 1, 5, and 9 cm proximal to the pylorus. The strain gauges were positioned in the antrum 2 cm proximal to each electrode. In 6 dogs, a sixlumen manometric tube with recording sites 2 cm apart was inserted through a small incision made in the lesser curvature of the proximal fundus of the stomach. The manometric tube, attached with a mercury rod at the end, was positioned at the comparable site in each dog. By manual palpation, the proximal end of the mercury rod was positioned immediately distal to the pylorus (Figure Table 1. The Counted Numbers of Gastric Contractions by Two Different Recording Systems Recording 5-15 min min min site Manometry ME Manometry ME Manometry ME Patient A M, M M Patient B M, M M Recording sites M " M2, M3 indicate three locations that are 12, 7, and 2 em proximal to the pylorus, respectively. The number under manometry indicates the frequency of contractions with amplitude > 25 mmhg recorded by intraluminal manometric tube technique. The number under ME (myoelectric activity) indicates the number of pacesetter potentials accompanied by action potential or second potential. The time in minutes indicates the time period after subcutaneous injection of bethanechol.

4 June 1984 ELECTROMECHANICAL ACTIVITY OF THE STOMACH 1463 '>~~l'" \ \ \ \ \ \ ~15g f----i 10 s Figure 4. Simultaneous recording of myoelectric activity (E) and tension change (S). The phasic contractions show parallel relationship with the pacesetter potentials (E). 2). For the manometric recording, the same quartz transducers and chart recorder were used as in human study. Blood pressure was continuously monitored using a Statham transducer (P23AC, Statham Instruments, Inc., Halto Rey, Puerto Rico) which was placed in the left carotid artery. The splenic artery was cannulated with a 19-9auge catheter (Intracath Desert Pharmaceutical Company, Sandy, Utah) and the artery distal to the cannulation site was tied with 00 silk. Through the catheter, 0.15 M saline or pharmacologic agents was infused. Epinephrine, 100 or 400 p,g. kg- 1 h-l, and phentolamine in an equimolar dose of epinephrine were administered i.a. in 11 dogs. In 6 dogs with electrodes, strain gauges, and intraluminal pressure recording system, simultaneous recordings of myoelectric and mechanical activity and intraluminal pressure were studied in response to i.a. administration of bethanechol, 2.5 mg' h- 1 which was dissolved in 50 cm 3 of 0.15 M saline. Results Studies in Humans After the subcutaneous administration of bethanechol, PSPs were followed by either action potential or prolonged negative deflection in the antra of the 2 subjects. The negative deflection following PSP was called second potential (16) and was believed to be the fusion of spike activities (action potential). Recently, the intracellular microelectrode recording revealed this negative deflection to be a plateau potential with increased amplitude and duration rather than to be the fusion of spike activities (17). The prolonged negative deflection was associated with a mechanical contraction of a large amplitude. This response occurred within 5 min of the injection of bethanechol and lasted for 50 min. The myoelectric activity was compared with mechanical activities recorded by manometry (Figure 3) by counting the frequency of PSPs with either action potential or second potential and the frequency of contractions with amplitude >25 mmhg. The results are depicted in Table 1. The myoelectric recording in 2 human subjects revealed that almost every PSP was accompanied by an action potential or second potential during the period starting 5 min after and extending to 50 min after subcutaneous bethanechol administration. This would indicate that continuous contractions occurred during the same period. During the period starting 15 min after and extending to 50 min after bethanechol administration, the manometric recording began to show contractions, but only at the two distal recording sites (the area between the pylorus and 7 cm proximal to the pylorus). However, the number of contractions recorded was <50% of the total number of action potentials occurring in the same period. Contractions were more frequently recorded at distal recording sites than at proximal sites. Table 2. The Counted Number of Gastric Contractions by Three Different Recording Systems During the lo-min Period of Bethanechol Infusion a Recording Strain sites Manometry ME gauge Dog 1 M, 0 30 M M M M M Dog 2 M, 0 5 M2 0 5 M3 0 3 M4 3 M M Dog 11 M, 0 15 M M M M M a Recording sites M, through M6 represent the locations at 12, 10, 8,6,4, and 2 em proximal to the pylorus, respectively. Thus, the recording sites M2, M4, and M6 were approximately in the same positions where electrodes were placed and the recording sites M " M3, and M5 correspond to the locations of three strain gauges. The numbers below each heading of manometry, ME (myoelectric activity). and strain gauge indicate the number of contractions recorded by the three recording methods. a The 10- min period is the time period from 10 to 20 min after bethanechol infusion began.

5 1464 YO U AND CHEY GASTROENTEROLOGY Vo!' 86, No. 6 s y',.. I' (I ~j, LJ, ''''VA.....,..,; ~ \,Y ' ~ 101 Figure 5. Simultaneous recording of myoelectric (El. tension (S), and manometric (M) activity in dog. There is a good parallel correlation between the myoelectric activities and tension changes. Correlation between the intraluminal manometry and myoelectric activities, however, was poor. Studies in Dogs Relationship between contractions and myoelectric activities. Phasic contractions of small amplitude were recorded during the control period in all 11 dogs. Each phasic contraction matched the corresponding PSP recorded in the same region of the antrum (Figure 4). The tension of the phasic contraction, however, was < 5 g. In the dogs that received bethanechol, only three studies from 3 dogs were satisfactory for analysis. The other three studies failed to produce acceptable recording for analysis because of technical difficulty. Action potentials or second potentials and phasic contractions in high amplitude (tension > 15 g) started to appear 10 min after the bethanechol infusion began. During the 10- min period, from 10 to 20 min after bethanechol infusion began, each recording system was compared by counting the PSPs accompanied by action potentials or second potentials, phasic contractions with tension > 10 g, and the contractions of amplitude >25 mmhg. As described in Table 2, the number of phasic contractions with increased tension recorded via strain gauge coincided precisely with the number of PSPs accompanied by action potential or second potential in all 3 dogs. The contractions recorded by manometry, however, were less in number than the contractions recorded by strain gauge at the same recording sites. During the same 10-min period, the amplitude of the majority of contractions recorded by manometry at the distal two recording sites (within 3 em from the pylorus) ranged from 200 to 250 mmhg (Figure 5). During the remaining 40-min period of bethanechol administration, both contractions recorded by strain gauges and action potential continued in the same magnitude throughout the infusion period as occurred in the first 10-min period. The manometric recording, however, failed to show contractions of high amplitude, mmhg, as were observed in the first min; instead, it showed simultaneous, low-amplitude contractions with amplitude ranging from 5 to 20 mmhg (Figure 6). Relationship between contraction and gastric dysrhythmia. In all 11 dogs, the effect of i.a. injec-

6 June 1984 ELECTROMECHANICAL ACTIVITY OF THE STOMACH 1465,,,, I,,." I,, " I,, " I,,,, I,,,, I,,,,J,, " I,, " I,,,, I,,,, I,,,, I,.. ' L ", I, II,J ",, I,,,, I,,,, I, ", i ',,, i ',,, i ' II ' i ' ", i ",, t---t 10 I Figure 6. The manometric recording of intraluminal pressure changes 20 min after bethanechol administration. It is characterized by simultaneous low-amplitude contractions, whereas myoelectric and tension activity show strong contractions. tion of epinephririe in a dose of lob jj-g' kg- 1 h- 1 on myoelectric and mechanical activity was studied. This dose of epinephrine was chosen because it consistently produced gastric dysrhythmia without significant change of systemic blood pressure. Blood pressure before epinephrine infusion was 137 ± 7.4 / 95 ± 4 mmhg; after epinephrine. infusion it was 142 ± 10/ 98 ± 9 inmhg. Ten of 11 dogs revealed gastric dysrhythmia intluding tachygastria, tachyarrhythmia, and bradygastria. Tachygastria was defined when PSP occurred reguiatly in a frequency of >7 cycles/min (Figure 7). Tachyarrhythmia (Figure 7) was defined by occurrence of increased frequency of PSP (>7 cycles/min) at irregular intervals. The bradygastria (Figure 7) was defined when the PSP occurred at a frequency <3 cycles/min. The dysrhythmia lasting 1-2 min occurred intermittently in these 10 dogs thtoughout the entire period of epinephrine infusion. In 1 remaining dog, dysrhythmia occurred only when the dose of epinephrine was increased to 400 jj-g' kg -1. h -1. During both the control period and the period of epinephrine administration, the frequency of phasic contractions recorded by strain gauges was equal to that of PSPs as long as the PSPs occurred at regular intervals and in normal frequency of 4-5 cycles/min (Figure 8). Whenever gastric dysrhythmia developed, phasic contractions disappeared and remained absent as long as dysrhythmia continued to occilr (Figure 8). As epinephrine injection was discontinued and the gastric dysrhythmia disappeared, the phasic contrac- TACHYGAstRIA TACHYARRHYTHMIA BRADYGAstRIA t:-----i 10 s Figure 7. The examples of typical gastric dysrhythmia including tachygastria, tachyarrhythmia, and bradygastria are shown.

7 1466 YOU AND CHEY GASTROENTEROLOGY Vol. 86. No. 6 NORMAL TACHYGASTRIA I-----i 10 s Figure 8. Normal phasic contractions paralleled normal myoelectric activities of the antrum in anesthetized dog (top strip). During tachygastria (bottom strip), phasic contractions were absent. esophagus or intestine. One has to realize, therefore, that the manometric method does not recognize all the contractile activity of the stomach. Motility changes that cannot be detected by manometry may well be important information for the assessment of a motility disorder such as gastric dysrhythmia. the present study also led us to believe that the dictum of "no action potential, no contraction" may not always be correct inasmuch as each PSP of the stomach was always accompanied by a contraction, although the amplitude of contraction was not strong enough to produce the luminal pressure changes that can be recorded by the manometry. The contractions of small amplitude accompanied by PSP were successfully recorded in in vitro study with smooth muscle segments (7) or small muscle strips (8). Furthermore, our work on in vivo stomach preparation is in good agreement with that of. others (6). The failure of recording the phasic contractions associat- tions reappeared in all the dogs. The dysrhythmia was prevented in all the dogs by phentolamine when it was administered simultaneously in an equimolar dose of 100 f.lg' kg- 1 h- 1 of epinephrine. However, phentolamine alone did not affect the spontaneous myoelectric and mechanical activities of the stomach. Although gastric dysrhythmia occurred in the distal antrum in all 11 dogs, 4 of the dogs developed gastric dysrhythmia in the proximal antrum also. In the remaining 7 dogs, the gastric dysrhythmia did not develop in the proximal antrum, but the Ihorphology of PSP changed from a triphasic configuration to a multiphasic one (Figure 9). However, the phasic contractions were associated with PSPs regardless of changes in the morphology of PSPs (Figure 9). Discussion Although intraluminal manometric recording for gastrointestinal motility has been used frequently for investigation of the physiology and pathophysiology of gastric motor function, the present study indicates that the manometry does not record all the contractile activity of the stomach in both humans and dogs; as many as 50% or more of the contractions recorded by a strain gauge technique could not be observed. This inadequate recording ability of gastric manometry may be attributed to the nontubular anatomy of the stomach, unlike the case of the I-----i 10 s Figure 9. The changes of phasic contraction corresponding to the changes of PSPs are shown. The top recording shows the phasic contractions corresponding to the PSPs of normal configuration, frequency, and rhythm. The middle recording shows the phasic contractions corresponding to the PSPs of multiphasic configuration but normal frequency and rhythm. The bottom recording shows the absence of phasic contractions during the period of tachyarrhythmia.

8 June 1984 ELECTROMECHANICAL ACTIVITY OF THE STOMACH 1467 ed with PSP in in vivo study may be attributed, in part, to use of less sensitive strain gauges than those that can record the contraction in similar experimental conditions. Because the functional significance of PSP has not been clarified, it has been described in other terminology such as basic electrical rhythm or slow wave; it has been determined, however, that PSP paces the gastric contractile activity in direction and in frequency. There has been little effort, however, to relate PSP to the motor function of the stomach, such as discharging the gastric content into the duodenum. It is conceivable that the omnipresent, peristaltic contraction of small amplitude may move the gastric contents from the proximal stomach toward the distal stomach with the help of increasing intragastric pressure when the proximal stomach is distended (18). The present study, however, was not undertaken to prove or disprove this possibility. The dose of epinephrine used in the present study is much higher than that used in another study (19). Epinephrine in such a high dose range was required to induce gastric dysrhythmia in the canine model we used. As gastric dysrhythmia developed, the phasic contractions associated with PSP completely disappeared. One may wonder whether or not this could be caused by direct effect of epinephrine on antral muscle tension. Three reasons can be offered to explain why epinephrine per se did not abolish the contractions associated with PSPs. First, the contractions disappeared only during gastric dysrhythmia. The contractions associated with PSP continued during epinephrine infusion as long as PSPs occurred regularly in normal frequency. Second, we made the same observation in 1 conscious dog prepared with chronically implanted electrodes and strain gauges in gastric antrum that exhibited spontaneous tachygastria without any pharmacologic manipulation (Figure 10). Third, in their intracellular microelectrode study, Morgan et al. (8) showed complete abolition of the second component of contraction, whereas there was marked decrease in the amplitude and duration of the potential plateaus after perfusion of norepinephrine in their muscle preparation chamber. The mechanism of epi:p.ephrine-induced gastric dysrhythmia is not known at the present time; however, the occurrence of gastric dysrhythmia was completely blocked by the a-receptor blocker, phentolamine, suggesting the presence of an a-receptor in the canine antral muscle. If PSPs possess an additional function besides pacing the stomach, such as moving the gastric contents, as we speculate, the gastric dysrhythmia could possibly interfere with the emptying function. Whether or not the gastric dysrhythmia affects the gastric emptying and thus NORMAL TACHYARRHYTHMIA I-----i 10. Figure 10. The simultaneous recording of myoelectric and tension activity in vivo during the period of normal myoelectric and spontaneous tachyarrhythmia in dog. During this period of tachyarrhythmia, the phasic contraction was absent, but reappeared when myoelectric activity returned to normal. causes symptom complexes of nausea, vomiting, and bloating remains to be answered. If the motility of human stomach is similar to that of canine stomach, patients with tachygastria (11-14) or bradygastria (13) may not exhibit phasic contractions that accompany PSP during the period of gastric dysrhythmia. One should recognize, therefore, the limitation of gastric manometry, and caution ought to be exercised in the interpretation of gastric dysrhythmia claimed to be recorded by a manometric method. References 1. Alvarez WC, Mahoney LJ. Action currents in stomach and intestine. Am J PhysioI1922;58: Garrett JM. Intraluminal detection of electrical activity of canine and human small intestine (thesis). Minneapolis: University of Minnesota, Carlson HC, Code CF, Nelson RA. Motor action of the canine gastroduodenal junction: a cineradiographic, pressure and electric study. Am J Dig Dis 1966;11: Kelly KA, Code CF, E1ueback LR. Patterns of canine gastric electrical activity. Am J Physiol 1969;217(2): Nelson TS, Eigenbrodt EH, Keoshian LA, Bunker C, Johnson L. Alteration in muscular and electrical activity of the stomach following vagotomy. Arch Surg 1967;94: Papasova M, Boev K. The slow potential and its relationship to the gastric smooth muscle contraction, In: Bulbring E, Shuba MF, eds. Physiology of smooth muscle, New York: Raven, 1976;209-16,

9 1468 YOU AND CHEY GASTROENTEROLOGY Vol. 86, No.6 7. You CH, Lee KY, Chey WY, Menguy R. In vitro myoelectric study of antral muscle from the patients of tachygastria. Dig Dis Sci 1980;25:A Morgan KF, Schmqlz PF, Szurszewski JH. The inhibitory effects of vasoactive intestinal polypeptide on the mechanical arid electrical activity of canine antral smooth muscle. J Physiol 1978;282: CodeCF, Marlett JA. Canine tachygastria. Mayo Clin Proc 1974;49: Telander RL, Morgan KG, Kruelen DL, et al. Human gastric atony with tachygastria and gastric retention. Gastroenterolo!lY 1978;75: You CH, Lee KY, Chey WY, Menguy R. Electrogastrogastric study pf patients with unexplained nausea, bloating and vomiting. Gastroenterology 1980;79: You CH, Lee KY, Chey WY. Gastric electromyography in normal and abnormal states in humans. In: Chey Wy, ed. Functional disorders of the digestive tract. New York: Raven, 198~;167-7~. 13. You CH, Chey WY, Lee KY, Menguy R, Bortoff A. Gastric and small intestinal myoelectric dy~rhythmia associated with chronic intractable nausea and vomiting. Ann Intern Med 1981;95: Chey WY, You CH, Lee KY, Menguy R. Gastric dysrhythmia: clinical aspects. In: Chey WY, ed. Functional disorders of the digestive tract. New York: Raven, 1983; Bass P, Wiley IN. Contractile force transducers for recording muscle activity in unanesthetized animal. J Appl Physiol 1972;32(4): Bass p, Code CF, Lambert EH. Electrical activity at the gastroduodenaljunction. Am J Physiol 1961;201: El-Sharkawy TY, Morgan KG, Szurszewski JH. Intracellular electrical activity of the canine and human gastric smooth muscle. J Physiol 1978;279: Wilbur BG, Kelly KA. Effect of proximal gastric, complete gastric, and truncal vagotomy on canine gastric electric activity, motility and emptying. Ann Surg 1973;178: Daniel ~E. The electrical and contractile activity pf the pyloris region in dogs and the effects of drugs. Gastroenterology 1965;49: