Electrical Activity of the Stomach: Clinical Implications
1986; Elsevier BV; Volume: 61; Issue: 3 Linguagem: Inglês
10.1016/s0025-6196(12)61851-5
ISSN1942-5546
AutoresChung H. Kim, Juan‐R. Malagelada,
Tópico(s)Intestinal and Peritoneal Adhesions
ResumoDisorders of gastrointestinal motility are increasingly being recognized with the aid of such innovative techniques as gastrointestinal manometry and radioscintigraphy. Applications of these techniques have expanded and refined our present understanding of the gut motility both in health and in disease. Recent studies have shown that disturbances of motility can be limited to a specific segment of the gut such as the stomach or can affect the entire gastrointestinal tract. Because gastrointestinal motility is controlled by electrical activity, increasing efforts are being made to characterize and quantify the underlying electrical disturbances in various disorders of gastrointestinal motility. In this article, we review the electrical basis of gastric motility and the clinical implications of gastric dysrhythmia. Disorders of gastrointestinal motility are increasingly being recognized with the aid of such innovative techniques as gastrointestinal manometry and radioscintigraphy. Applications of these techniques have expanded and refined our present understanding of the gut motility both in health and in disease. Recent studies have shown that disturbances of motility can be limited to a specific segment of the gut such as the stomach or can affect the entire gastrointestinal tract. Because gastrointestinal motility is controlled by electrical activity, increasing efforts are being made to characterize and quantify the underlying electrical disturbances in various disorders of gastrointestinal motility. In this article, we review the electrical basis of gastric motility and the clinical implications of gastric dysrhythmia. Disturbances in the motility of the gut have been detected in patients with "functional-type" disorders such as idiopathic gastroparesis and intestinal pseudo-obstruction.1Malagelada J-R Delayed gastric emptying: pathophysiology, diagnosis and therapy.in: Dubois A Castell DO Esophageal and Gastric Emptying. CRC Press, West Palm Beach, Florida1984: 95-107Google Scholar Patients with such conditions often have symptoms of chronic nausea, vomiting, and abdominal pain without an anatomic lesion demonstrable on radiologic or endoscopic examination. Techniques such as manometry and radioscintigraphy have demonstrated that these patients can have disturbances of motility in a specific segment of (for instance, the stomach) or throughout the gastrointestinal tract. Because gastrointestinal motility is controlled by electrical activity, efforts are increasingly being directed at quantification and characterization of underlying electrical disturbances of the gut in various disorders of gastrointestinal motility. In this article, we review the electrical activity of the stomach in health and in disease states in an attempt to correlate electrical events at the cellular level with clinical settings in which gastric motor function is abnormal. Spontaneous and rhythmic electrical potentials have been recorded from the stomach of experimental animals and humans since the turn of the century.2Szurszewski JH Electrical basis for gastrointestinal motility.in: Johnson LR Physiology of the Gastrointestinal Tract. Vol 2. Raven Press, New York1981: 1435-1466Google Scholar The gastric electrical potentials are myogenic, and they are generated by depolarization and subsequent repolarization of the smooth muscle cell membrane. The timing and characteristics of these potentials are modulated by neurohormonal factors.3El-Sharkawy TY Morgan KG Szurszewski JH Intracellular electrical activity of canine and human gastric smooth muscle.J Physiol (Lond). 1978; 279: 291-307Crossref Scopus (120) Google Scholar, 4Szurzsewski JH Mechanism of action of pentagastrin and acetylcholine on the longitudinal muscle of the canine antrum.J Physiol (Lond). 1975; 252: 335-361Google Scholar Early recordings of gastric potentials were obtained with large extracellular electrodes, and the recorded potentials were complex in shape because they reflected potential changes from thousands of smooth muscle cells in the region of the electrode. With the development of the intracellular microelectrode in recent years, quantitative analysis of the fluctuating membrane potential of a single smooth muscle cell became possible. Subsequent utilization of this technique not only clarified the complex potential changes seen on extracellular recordings but also unraveled the mechanism of electromechanical coupling in gastric smooth muscle. The stomach can be divided into two regions on the basis of its electrical activity.5Hinder RA Kelly KA Human gastric pacesetter potential: site of origin, spread, and response to gastric transection and proximal gastric vagotomy.Am J Surg. 1977; 133: 2933Abstract Full Text PDF Scopus (243) Google Scholar, 6Kelly KA Code CF Elveback LR Patterns of canine gastric electrical activity.Am J Physiol. 1969; 217: 461-470PubMed Google Scholar The proximal portion of the stomach, which encompasses the fundus and the oral third of the gastric corpus, exhibits a sustained and nonphasic electrical activity. The rest of the stomach (the distal portion) demonstrates a well-defined, phasic electrical activity. In the distal part of the stomach, the membrane potential of smooth muscle cells is not maintained at a stable level but is interrupted by an omnipresent, recurring variation in electrical potential. These potentials have been labeled as "slow waves," "basic electric rhythm," "control potentials," or "pacesetter potentials," all of which terms refer to the same phenomenon. Gastric slow waves are generated from an area in the midcorpus along the greater curvature.5Hinder RA Kelly KA Human gastric pacesetter potential: site of origin, spread, and response to gastric transection and proximal gastric vagotomy.Am J Surg. 1977; 133: 2933Abstract Full Text PDF Scopus (243) Google Scholar, 7Kelly KA Code CF Canine gastric pacemaker.Am J Physiol. 1971; 220: 112-118PubMed Google Scholar This area behaves as a gastric pacemaker because it has the highest rate of slow-wave production and sets the "pace" for the entire stomach. From their site of origin, the slow waves propagate circumferentially and longitudinally to the pylorus at a rate of 3 cycles per minute in humans5Hinder RA Kelly KA Human gastric pacesetter potential: site of origin, spread, and response to gastric transection and proximal gastric vagotomy.Am J Surg. 1977; 133: 2933Abstract Full Text PDF Scopus (243) Google Scholar and 5 to 6 cycles per minute in dogs6Kelly KA Code CF Elveback LR Patterns of canine gastric electrical activity.Am J Physiol. 1969; 217: 461-470PubMed Google Scholar (Fig. 1). The slow waves, however, do not propagate retrogradely to the proximal part of the stomach. Gastric slow waves propagate myogenically and do not depend on special conduction fibers as cardiac potentials do. In fact, no such conduction system is found in the stomach. The gastric smooth muscle cells communicate with one another—electrically, that is—through gap junctions.8Gabella G Structure of muscles and nerves in the gastrointestinal tract.in: Johnson LR Physiology of the Gastrointestinal Tract. Vol 1. Raven Press, New York1981: 197-241Google Scholar Gap junctions are areas in which the outer lamellae of the muscle cells are fused or are closely apposed, and they provide a low-resistance pathway between cells. Therefore, changes in the membrane potential in any cell are shared by the adjacent cells through the gap junctions. Gastric contraction is a mechanical manifestation of an electrical event that occurs at the surface membrane of smooth muscle cells. As an aid for understanding the mechanism of electromechanical coupling, we will first review the shape of gastric slow waves. The shape of gastric slow waves depends on the method of recording. Intracellular recordings show that each slow wave is characterized by an initial upstroke potential and a subsequent plateau potential. On extracellular recordings, each slow wave appears as a composite of a triphasic (positive-negative-positive) potential complex and an isopotential segment (Fig. 2). The triphasic potential complex is sometimes referred to as the initial potential. An example of a normal extracellular electromyo-gram of the canine stomach is shown in Figure 3.Fig. 3Normal electrical activity of the canine stomach (extracellular recording). Note well-defined and phasic slow waves, which propagate from the midcorpus all the way to the distal antrum in an antegrade fashion. The rate of the slow waves is 5 cycles per minute in the dog.View Large Image Figure ViewerDownload (PPT) Gastric action potentials produce contraction, but gastric slow waves do not. In the stomach, the term "action potential" refers to a potential change that causes the smooth muscle to contract. Using the technique of simultaneous mechanical and intracellular microelectrode recordings, Morgan and Szurszewski9Morgan KG Szurszewski JH Mechanisms of phasic and tonic actions of pentagastrin on canine gastric smooth muscle.J Physiol (Lond). 1980; 301: 229-242Google Scholar demonstrated that a gastric action potential triggers a mechanical response by increasing the size of the plateau potential above a certain threshold. The plateau potential of an action potential looks like a "depression" on the extracellular electromyogram, and it is referred to as the second potential (Fig. 2). In the distal antrum, one or more depolarizing potentials called "spikes" can be superimposed on the plateau potential. Excitatory agents of gastric contraction such as acetylcholine and pentagastrin increase the magnitude of contraction by increasing the amplitude of the plateau potential above the mechanical threshold.2Szurszewski JH Electrical basis for gastrointestinal motility.in: Johnson LR Physiology of the Gastrointestinal Tract. Vol 2. Raven Press, New York1981: 1435-1466Google Scholar, 4Szurzsewski JH Mechanism of action of pentagastrin and acetylcholine on the longitudinal muscle of the canine antrum.J Physiol (Lond). 1975; 252: 335-361Google Scholar Conversely, inhibitory agents such as norepinephrine and prostaglandin E2 reduce the force of contraction by decreasing the amplitude of the plateau potential.2Szurszewski JH Electrical basis for gastrointestinal motility.in: Johnson LR Physiology of the Gastrointestinal Tract. Vol 2. Raven Press, New York1981: 1435-1466Google Scholar, 10Sanders K Menguy R Chey W You C Lee K Morgan K Kreulen D Schmalz P Muir T Szurszewski J One explanation for human antral tachygastria (abstract).Gastroenterology. 1979; 76: 1234Google Scholar Therefore, the force of gastric contraction is directly related to the duration and the amplitude of the plateau potential. Disturbances in the normal gastric electrical activity were first reported in dogs by Code and Marlett.11Code CF Marlett JA Canine tachygastria.Mayo Clin Proc. 1974; 49: 325-332PubMed Google Scholar They described two types of abnormalities: slow waves that are unusually fast in rate and slow waves that are normal in rate but highly irregular in rhythm. They designated these abnormalities tachygastria and arrhythmia, respectively. Subsequently, bradygastria was added to the list of gastric dysrhythmias; it refers to slow waves that are abnormally slow in rate. Tachygastria and bradygastria have distinct electrical characteristics. Tachygastria usually originates from an ectopic focus in the distal antrum, and its slow waves often propagate in a retrograde fashion contrary to the usual antegrade manner. Each episode of tachygastria is followed by a pause that appears as an electrically "silent" period on the extracellular electromyogram (Fig. 4). In contrast, bradygastria usually does not arise from a discrete area in the stomach; rather, it appears in both the corpus and the antrum simultaneously, and its slow waves usually propagate antegradely (Fig. 5).Fig. 5An example of drug-induced canine bradygastria (extracellular recording). Note that shortly after a bolus injection of met-enkephalin (arrow) slow waves appear abnormally slow in both the corpus and the antrum simultaneously. Bradygastric slow waves are shown to propagate in the usual antegrade manner.View Large Image Figure ViewerDownload (PPT) Although the etiologic mechanism of gastric dysrhythmia is currently unknown, it can be induced pharmacologically both in humans and in animals under experimental conditions. Agents such as epinephrine, glucagon, met-enkephalin, β-endorphin, prostaglandin E2, secretin, and insulin have all been demonstrated to cause gastric dysrhythmia.12Kim CH, Azpiroz F, Malagelada J-R: Characteristics of spontaneous and drug-induced gastric dysrhythmias in a chronic canine model. Gastroenterology (in press)Google Scholar, 13Stoddard CJ Smallwood RH Duthie HL Electrical arrhythmias in the human stomach.Gut. 1981; 22: 705-712Crossref PubMed Scopus (112) Google Scholar The characteristics of tachygastria and bradygastria induced by these agents are similar to those that occur spontaneously.12Kim CH, Azpiroz F, Malagelada J-R: Characteristics of spontaneous and drug-induced gastric dysrhythmias in a chronic canine model. Gastroenterology (in press)Google Scholar The fact that such a variety of substances with diverse chemical structures can cause similar electrical disturbances in the stomach raises the possibility that they may act through a common paracrine pathway. A strong, though yet unproven, candidate is the intramural synthesis and release of endogenous prostaglandins.10Sanders K Menguy R Chey W You C Lee K Morgan K Kreulen D Schmalz P Muir T Szurszewski J One explanation for human antral tachygastria (abstract).Gastroenterology. 1979; 76: 1234Google Scholar Gastric dysrhythmias have been described in a variety of clinical conditions (Table 1). Most of the published studies, however, have been isolated case reports, and the role of gastric dysrhythmia in human disease has yet to be examined with careful scientific scrutiny. The first well-documented report of tachygastria in humans was published in 1978. Telander and associates14Telander RL Morgan KG Kreulen DL Schmalz PF Kelly KA Szurszewski JH Human gastric atony with tachygastria and gastric retention.Gastroenterology. 1978; 75: 497-501PubMed Scopus (167) Google Scholar described a 5-month-old male infant who was debilitated from severe gastric retention and had symptoms of intractable nausea, vomiting, and weight loss. The symptoms were attributed to impaired motor function of the stomach, and they were unrelieved by conventional medical therapy and surgical procedures such as pyloroplasty or gastrojejunostomy. Subsequently, the patient underwent resection of the distal three fourths of the stomach and gastrojejunostomy, after which the symptoms dramatically subsided. When the surgical gastric tissue was carefully studied in vitro by means of intracellular microelectrode techniques, abnormally fast slow waves (occurring at a rate of 5 to 20 cycles per minute, in contrast with the normal rate of 3 cycles per minute) were detected. Furthermore, addition of excitatory stimulants to the gastric smooth muscle failed to generate plateau potentials, and no contractions were noted. This detailed account of abnormal electrophysiologic findings at the cellular level provided a rational explanation for the clinical problem of gastric atony in this patient.Table 1Clinical Conditions and Other Factors Associated With Gastric Dysrhythmias*Tachygastria, bradygastria, and arrhythmia.Condition or factorReferencesIdiopathic gastroparesis14Telander RL Morgan KG Kreulen DL Schmalz PF Kelly KA Szurszewski JH Human gastric atony with tachygastria and gastric retention.Gastroenterology. 1978; 75: 497-501PubMed Scopus (167) Google Scholar, 15You CH Chey WY Lee KY Menguy R Bortoff A Gastric and small intestinal myoelectric dysrhythmia associated with chronic intractable nausea and vomiting.Ann Intern Med. 1981; 95: 449-451Crossref PubMed Scopus (141) Google Scholar, 16You CH Lee KY Chey WY Menguy R Electrogastrographic study of patients with unexplained nausea, bloating, and vomiting.Gastroenterology. 1980; 79: 311-314PubMed Google ScholarSecondary gastroparesis Diabetes mellitus17Abell TL Camilleri M Malagelada J-R High prevalence of gastric electrical dysrhythmias in diabetic gastroparesis (abstract).Gastroenterology. 1985; 88: 1299PubMed Google Scholar Anorexia nervosa18Abell TL Lucas AR Brown ML Malagelada J-R Gastric electrical dysrhythmias in anorexia nervosa (AN) (abstract).Gastroenterology. 1985; 88: 1300Google ScholarGastric ulcer19Geldof H van der Schee EJ van Blankenstein M Grashuis JL Gastric dysrhythmia: an electrogastrographic study (abstract).Gastroenterology. 1983; 84: 1163Google ScholarGastric adenocarcinoma5Hinder RA Kelly KA Human gastric pacesetter potential: site of origin, spread, and response to gastric transection and proximal gastric vagotomy.Am J Surg. 1977; 133: 2933Abstract Full Text PDF Scopus (243) Google ScholarMiscellaneous Asymptomatic persons13Stoddard CJ Smallwood RH Duthie HL Electrical arrhythmias in the human stomach.Gut. 1981; 22: 705-712Crossref PubMed Scopus (112) Google Scholar, 17Abell TL Camilleri M Malagelada J-R High prevalence of gastric electrical dysrhythmias in diabetic gastroparesis (abstract).Gastroenterology. 1985; 88: 1299PubMed Google Scholar, 18Abell TL Lucas AR Brown ML Malagelada J-R Gastric electrical dysrhythmias in anorexia nervosa (AN) (abstract).Gastroenterology. 1985; 88: 1300Google Scholar Postoperative period20Sarna SK Bowes KL Daniel EE Post-operative gastric electrical control activity (ECA) in man.in: Daniel EE Proceedings of the Fourth International Symposium on Gastrointestinal Motility. Mitchell Press, Vancouver, Canada1973: 73-83Google Scholar, 21Bertrand J Dorval ED Metman EH de Calan L Ozoux JP Electrogastrography and serosal electrical recording of the antrum after proximal vagotomy in man (abstract).Gastroenterology. 1984; 86: 1026Google Scholar* Tachygastria, bradygastria, and arrhythmia. Open table in a new tab The association between tachygastria and abnormal gastric motor function was further substantiated by another well-documented report that was published in 1981.15You CH Chey WY Lee KY Menguy R Bortoff A Gastric and small intestinal myoelectric dysrhythmia associated with chronic intractable nausea and vomiting.Ann Intern Med. 1981; 95: 449-451Crossref PubMed Scopus (141) Google Scholar In that report, a 26 year-old woman with persistent nausea, vomiting, and abdominal pain was found to have antral tachygastria and severe impairment of antral motor function. This patient also required a subtotal gastrectomy for relief of her symptoms. In another study, You and associates16You CH Lee KY Chey WY Menguy R Electrogastrographic study of patients with unexplained nausea, bloating, and vomiting.Gastroenterology. 1980; 79: 311-314PubMed Google Scholar reported that gastric dysrhythmias were found in 9 of 14 patients, all of whom had unexplained nausea, vomiting, and epigastric bloating for periods that ranged from 5 months to 10 years. The role of gastric dysrhythmia in human disease was further suggested by its high prevalence in patients who suffer from gastroparesis in association with diabetes mellitus oranorexia nervosa.17Abell TL Camilleri M Malagelada J-R High prevalence of gastric electrical dysrhythmias in diabetic gastroparesis (abstract).Gastroenterology. 1985; 88: 1299PubMed Google Scholar, 18Abell TL Lucas AR Brown ML Malagelada J-R Gastric electrical dysrhythmias in anorexia nervosa (AN) (abstract).Gastroenterology. 1985; 88: 1300Google Scholar Gastric dysrhythmias do not occur exclusively in stomachs with impaired motor function. They also have been detected in asymptomatic persons,13Stoddard CJ Smallwood RH Duthie HL Electrical arrhythmias in the human stomach.Gut. 1981; 22: 705-712Crossref PubMed Scopus (112) Google Scholar, 17Abell TL Camilleri M Malagelada J-R High prevalence of gastric electrical dysrhythmias in diabetic gastroparesis (abstract).Gastroenterology. 1985; 88: 1299PubMed Google Scholar, 18Abell TL Lucas AR Brown ML Malagelada J-R Gastric electrical dysrhythmias in anorexia nervosa (AN) (abstract).Gastroenterology. 1985; 88: 1300Google Scholar during the immediate postoperative period,20Sarna SK Bowes KL Daniel EE Post-operative gastric electrical control activity (ECA) in man.in: Daniel EE Proceedings of the Fourth International Symposium on Gastrointestinal Motility. Mitchell Press, Vancouver, Canada1973: 73-83Google Scholar, 21Bertrand J Dorval ED Metman EH de Calan L Ozoux JP Electrogastrography and serosal electrical recording of the antrum after proximal vagotomy in man (abstract).Gastroenterology. 1984; 86: 1026Google Scholar and in a variety of unrelated clinical conditions.5Hinder RA Kelly KA Human gastric pacesetter potential: site of origin, spread, and response to gastric transection and proximal gastric vagotomy.Am J Surg. 1977; 133: 2933Abstract Full Text PDF Scopus (243) Google Scholar, 19Geldof H van der Schee EJ van Blankenstein M Grashuis JL Gastric dysrhythmia: an electrogastrographic study (abstract).Gastroenterology. 1983; 84: 1163Google Scholar In such circumstances, however, gastric dysrhythmias tend to be transient and not persistent. Whether gastric dysrhythmias are directly responsible for abnormal motor function of the stomach and the production of dyspeptic symptoms is not entirely clear at the present time. The presence of persistent gastric dysrhythmia in a patient with dyspeptic symptoms, however, may indicate an underlying motor dysfunction of the stomach and may warrant further investigation with use of such techniques as gastrointestinal manometry and radioscintigraphy. We thank Dr. Thomas L. Abell for his thorough critique and helpful suggestions during preparation of the manuscript and Ms. Velda R. Woyczik for secretarial assistance.
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