The Future and Electrogastrography

The 3-cycles per minute (cpm) gastric pacesetter potential is a fundamental electrical phenomenon of the stomach. This low-frequency biorhythm is the basis for normal neuromuscular function of the stomach. In regard to the origins and the various neural and hormonal influences that affect the 3-cpm rhythm, many mysteries remain. Ongoing and future inquiries into the very nature of rhythmicity will provide deeper understanding of gastric myoelectrical activity and the electrical activity detected in the electrogastrogram (EGG). The role of knockout mice that lack interstitial cells of Cajal will be increasingly important in understanding the crucial role of rhythmic electrical events in normal and abnormal neuromuscular function of the stomach. These and other animal studies will also continue to help clinicians understand the deficits in gastric neuromuscular function caused by electrical dysrhythmias. A delicate balance maintains normal 3-cpm activity. Stomach electrical rhythmicity is rather unstable during fasting, for example, compared with the rhythmic 3-cpm electrical events and contractile events that occur in the postprandial period. What mechanisms produce these fasting and postprandial electrical changes? Are neural or hormonal circuits most critical? Are extrinsic or intrinsic nerves the most important? Studies of fasting and postprandial EGG activity may offer insights into sensations of hunger and satiety. The EGG signal is responsive to brain-gut interactions such as the cephalic-vagal reflex. Sham feeding studies with healthy subjects indicated that the sight, smell, and taste of food significantly increased 3- cpm activity. However, in subjects who indicated that the sham feeding experience was disgusting, no increase in 3-cpm activity occurred in this situation. Future studies of patients with eating disorders such as bulimia or anorexia nervosa using EGG recording methods may reveal new insights into the pathophysiology of eating disorders and be of value in monitoring the progress of treatment. Different EGG patterns induced by different meals reflect the different gastric neuromuscular work required to receive, mix, and empty the specific meal. Characteristics of the EGG signal from frequency to amplitude may also correlate with perceptions of stomach fullness, hunger, or satiety.

Tachygastrias

Gastric dysrhythmias are abnormal myoelectrical signals originating from the stomach. As recorded from cutaneous or serosal electrodes, bradygastrias range from 0 to 2.5 cycles per minute (cpm). Bradygastrias and mixed gastric dysrhythmias are reviewed in detail in Chapter 8. Tachygastrias range from 3.75 to l0.0cpm. The normal duodenal pacesetter potential ranges from 12 to 14 cpm. In this chapter, tachygastrias are reviewed in detail. Multiple metabolic mechanisms and neural-hormonal pathways influence gastric myoelectrical activity. The normal activities of enteric neurons, smooth muscle, hormones, and extrinsic nerves influence the ongoing activity of the interstitial cells of Cajal (ICCs), the pacemaker cells of the stomach. In healthy subjects, the frequency of gastric myoelectrical activity may vary from approximately 2.5 to 3.7cpm, depending on specific circumstances or provocative tests (Fig. 7.1). Specific diseases and disorders, with their specific pathophysiologies, may adversely affect gastric myoelectrical activity and are associated with gastric dysrhythmias. For example, many patients with type I and II diabetes have gastric dysrhythmias, and in healthy subjects, hyperglycemia itself produces gastric dysrhythmias. Gastric dysrhythmias occur when the ICCs are damaged or dysfunctional or when enteric neurons, circular smooth muscle cells (and perhaps longitudinal muscle activity), and extrinsic nerve activity from the parasympathetic and sympathetic nervous system input to the stomach are abnormal. Endocrine, neurocrine, and paracrine activities may also affect interstitial cells, enteric neurons, and smooth muscle and thereby affect gastric myoelectrical rhythms,21 shifting electrical activity to bradygastrias (0-2.5cpm) or tachygastrias (3.7- l0.0cpm) as shown in Figure 7.1. All of these influences interact to maintain normal gastric myoelectrical activity during baseline periods and in response to meals or other provocative stimuli. Stimuli that provoke stomach neuromuscular activity range from motion and the illusion of motion to emotionally challenging situations (disgust, anger) to the cephalic phase of digestion (vagal activation in the presence of appetizing food) to the relaxation, contraction, and coordination of stomach neuromuscular responses during and after the ingestion of a wide variety of solid and liquid foodstuffs. Thus, there are many gut-brain and brain-gut interactions to consider when evaluating gastric myoelectrical events during EGG recordings at baseline and after provocative stimuli.

Clinical Applications of Electrogastrography

Electrogastrography methods have been used in many clinical studies over the past 80 years. In 1922,Alvarez predicated that electrical abnormalities of the stomach may be related to gastrointestinal (GI) symptoms and abnormal gastric function. In 1980, antral dysrhythmias were recorded with mucosal electrodes in a series of patients with unexplained nausea and vomiting. These gastric dysrhythmias were 6— to 7—cycles per minute (cpm) tachygastrias, bu there were also very irregular rhythms that changed from bradygastria to tachygastria (mixed dysrhythmias or tachyarrhythmias). Bradygastrias also were recorded in patients with unexplained nausea and vomiting. Further studies showed a relationship between the presence of nausea and gastric dysrhythmias during motion sickness, in nausea and vomiting of pregnancy, and in patients with idiopathic and diabetic gastroparesis. Infusion of a variety of drugs and physical distention of the antrum also induced gastric dysrhythmias and symptoms of nausea. Ischemic gastroparesis with gastric dysrhythmias due to chronic mesenteric ischemia is an unusual cause of chronic nausea and vomiting. Ischemic gastroparesis is important to recognize because after revascularization the symptoms resolved, the gastric dysrhythmias were eradicated and normal 3-cpm EGG activity and normal gastric emptying were restored. Thus, gastric dysrhythmias are found in many disorders in which nausea and vomiting are prominent symptoms. Clinical conditions associated with gastric dysrhythmias were reviewed. Finally, a variety of drugs and nondrug therapies convert gastric dysrhythmias to normal 3-cpm gastric myoelectrical rhythms and the correction of the gastric dysrhythmia correlates with improvement in symptoms. Taken together, these findings indicate that gastric dysrhythmias are objective, pathophysiological events related to the upper GI symptoms, especially nausea and dysmotility-like functional dyspepsia symptoms such as early satiety, fullness, and vomiting. The recording of gastric dysrhythmias is an important tool for the clinician when patients have symptoms that suggest gastric dysfunction such as unexplained nausea, bloating, postprandial fullness, and early satiety. On the other hand, these upper GI symptoms are nonspecific, and diseases or disorders of other organ systems such as esophagus, gallbladder, small bowel, colon, and non-GI diseases must be considered.

Bradygastrias and Mixed Dysrhythmias

Bradygastrias are low-frequency electrogastrogram (EGG) waves that range from approximately 1.0 to 2.5 cycles per minute (cpm) . Some bradygastria waves are high amplitude and occupy the full scale of the EGG recording channel; others are very low amplitude and appear to be almost flatline. Bradygastrias have been recorded in patients with functional dyspepsia, diabetic and idiopathic gastropathy, and nausea of pregnancy. These patients have symptoms of abdominal discomfort, fullness, nausea, and vomiting. In this chapter, the causes of bradygastria patterns are reviewed and examples of bradygastrias are shown. EGGs also may have increased bradygastria and tachygastria waves, a pattern termed a mixed dysrhythmia. The exact origin of bradygastrias has been difficult to determine. In certain circumstances, the antrum contracts at 1.5 to 1.8 contractions per minute rather than the more recognized 3-per-minute contractions. Figure 8.1 indicates the relationship between EGG waves and low-frequency antral peristaltic contractions recorded from an intraluminal pressure sensing device during fasting and after infusion of erythromycin in healthy individuals. The antral contractions were recorded 3 and 1.5 cm from the pylorus. During fasting, 2-cpm EGG waves were present and correlated with 2-per-minute antral contractions. Each of these low-frequency contractions was associated with a low-frequency EGG wave (a negative deflection followed by a positive deflection). Irregular antral attractions also occur during fasting and may be reflected in the EGG as 1- to 2-cpm EGG waves. After erythromycin infusion, the EGG waves occurred at 1.0 to 1.5cpm and correlated with stronger antral contractions that occurred at the same frequency: 1.0 to 1.5 per minute. Thus, the bradygastria EGG frequencies correlated with the low-frequency antral contractions during fasting and after infusion of erythromycin. These studies indicate that, under certain conditions, bradygastria waves reflect low-frequency antral contractions. The fundus of the stomach normally contracts slowly at a rate from 0.5 to 1 contraction per minute.15 Thus, the low-frequency contractile activity of the fundus may also be reflected in the low frequency EGG signals in certain situations.

Analysis of the Electrogastrogram

The analysis of electrogastrogram (EGG) recordings involves an initial visual inspection of the signal to assess the quality of the signal, identification of artifacts, and selection of the minutes of EGG signal to analyze visually and by computer. This chapter discusses an approach to analyses of the EGG for clinical and research studies. All raw EGG recordings must be visually inspected to identify 3- cycles per minute (cpm) signals, gastric dysrhythmias, and any artifacts in the signal. Certain characteristics of the EGG can be determined and qualitative judgments can be made on the basis of visual inspection of an EGG record. Artifact-free minutes of the EGG signal must be selected for use in analyses that are generated by computer programs. When inspecting the EGG recording, there are several important questions to ask: 1. Is the baseline EGG recording rhythmic or dysrhythmic? 2. Are bradygastria, normal, or tachygastria frequencies identifible? 3. Is the amplitude of the EGG signal low, medium, or high? 4. After a provocative stimulus, does the EGG signal become more or less rhythmic? For example, Figure 5.1 shows a normal 3-cpm EGG signal that shifts to a tachygastria as the subject experienced nausea in a rotating optokinetic drum. Clinically relevant gastric dysrhythmias are persistent and last at least 3 to 5 minutes, usually much longer. 5. Is there a normal increase in the amplitude of the EGG after eating? Figure 5.2 shows an EGG recorded from a healthy subject before and after eating a test breakfast meal. Note the obvious increase in EGG amplitude at 3 cpm after the ingestion of food. 6. Are there artifacts in the EGG signal associated with movements of limbs or body or changes in respiration? Portions of the EGG recording with artifacts must be identified and not submitted for computer analysis; otherwise, erroneous data quantitative data will be generated. Thus, frequency and amplitude of the raw EGG signal during baseline and in response to the test stimulus should be first assessed visually. The visual inspection of the EGG record determines the general quality of the EGG signal and the presence of any artifacts.

Recording the Electrogastrogram

Electrogastrograms (EGGs) are recorded by placing electrocardiogram (ECG)-type electrodes on the surface of the epigastrium. The EGG is one of several biological signals that can be recorded from the electrodes on the epigastrium. Some of these signals, like the EGG, are much stronger than the EGG. The EGG signal is relatively low amplitude, ranging from approximately 100 to 500 (μV. Thus, the EGG signal must be properly amplified and filtered for quality recordings. To reduce baseline drift and to remove unwanted cardiac and respiratory signals, a 0.016-Hz high-pass filter and a 0.25-Hz low-pass filter are used. These filters create a bandpass, or window, from approximately 1 cycle per minute (cpm) to 15cpm through which the desired gastric myoelectrical signals pass during the EGG recording. In this chapter, the equipment needed to record the EGG, the EGG recording procedure, and how to identify and reduce artifacts in EGG recordings are discussed. For additional information on the acquisition and analysis of EGG data, the reader is referred to several reviews and texts. High-quality, fresh, disposable electrodes such as those used for electrocardiogram (EGG) recording are recommended. To minimize artifacts in the EGG recording caused by electrode movement on the skin, it is best to use electrodes that adhere very well to the skin (e.g., Cleartrace; ConMed Corp., Utica, NY; or BioTac; Graphic Controls, Inc., Buffalo, NY). Reusable silver/silver chloride electrodes are available (e.g., 1081 Biode; UFI, Morro Bay, CA). The size of the electrode surface is not important, but the electrical stability of the electrode is important. The electrodes should show little bias or offset potential because the EGG signal is relatively low amplitude and low frequency. A high-quality recording system is needed to amplify and process the 100 to 500-μV EGG signal that ranges from 1.0 to 15.0 cpm. Some older physiological polygraphs have appropriate amplifiers and filters that can be used to record the EGG. Several medical device companies produce complete EGG recording and analysis systems that include appropriate amplifiers and filters with analog-to-digital boards that digitize the EGG signal for analysis with software (e.g., 3CPM Company, Crystal Bay, NV; Medtronic, Shoreview, MN).

Physiological Basis of Electrogastrography

In this chapter, the anatomical, functional, and in vivo myoelectrical characteristics of the normal stomach are reviewed. The anatomical regions of the stomach are shown in Figure 3.1. Major areas are the fundus, the body (corpus), antrum, and pyloroduodenal area. Extrinsic innervation of the stomach is provided by the vagus nerve and splanchnic nerves. The pacemaker region is shown on the greater curvature of the stomach between the fundus and the corpus. From the pacemaker region, spontaneous electrical depolarization and repolarization occurs and generates the myoelectrical waves that are termed the gastric pacesetter potentials, or slow waves. The prominent muscle layers of the stomach are the circular and the longitudinal muscle layers (see Fig. 3.1, middle). The oblique muscle layer is included in the muscularis. Between these smooth muscle layers lie the neurons of the myenteric plexus, the gastric components of the enteric nervous system. Afferent neurons, interneurons, and postganglionic parasympathetic neurons all have synaptic interactions in the myenteric plexus. Intrinsic neurons and extrinsic excitatory and inhibitory neurons from the vagus nerve and splanchnic nerves, intraluminal contents, and hormones modulate contraction and relaxation of the smooth muscle in the different regions of the stomach. Important anatomical and functional relationships exist among the circular smooth muscle layer, the myenteric neurons, and the interstitial cells of Cajal (ICCs) (see Fig. 3.1, bottom). The ICCs are the pacemaker cells, the cells that spontaneously depolarize and repolarize and set the myoelectrical rhythmicity of the stomach and other areas of the gastrointestinal tract. The interstitial cells are electrically coupled with the circular muscle cells. Low-amplitude rhythmic circular contractions occur at the pacemaker rhythm. Rhythmicity and contractility of the circular muscle layer are modulated by ongoing activity excitatory and inhibitory of myenteric neurons that synapse with the interstitial cells. The interstitial cells have a variety of other receptors. Electrocontractile activities of the gastric smooth muscle are modified by neuronal and hormonal inputs appropriate for fasting and specific postprandial conditions. Control of rhythmicity may be modulated by a variety of stimuli that affect the interstitial cells and is a focus of intense investigation.

Properties of Electrical Rhythmicity in the Stomach

Gastric peristaltic contractions are the basis for emptying of solids from the stomach. These events begin in the mid to high corpus region, develop into a ring around the stomach, and spread down the length of the stomach to the pylorus. The pressure wave resulting from gastric peristalsis pushes the contents of the stomach toward the pyloric sphincter, but a nearly simultaneous contraction of the ring of muscle in the pyloric canal and the terminal antrum ultimately forces much of the food in the retrograde direction, toward the body of the stomach. Sheer forces that develop as a result of this forceful retropulsion cause mechanical disruption of solid particles. Repetitive peristaltic contractions (e.g., in the human these events occur about 3 times per minute), over a period of time, reduces ingested foods to small particles. The action of gastric peristalsis in the distal stomach facilitates emptying and the reduced particle diameter aides in chemical digestion of foods in the small intestine. Pathophysiological conditions that disrupt or disorganize gastric peristalsis can impair or delay normal gastric emptying. Gastric peristaltic contractions result from depolarization of the plasma membranes of smooth muscle cells. For many years it has been known that gastric muscles display periodic (or rhythmic) electrical activity in which membrane potential oscillates between negative potentials and more depolarized levels. The oscillations in membrane potential are known as electrical slow waves (see Color Figs. 2.1 and 2.2 in separate color insert). Slow waves are generated within the tunica muscularis of the proximal corpus along the greater curvature of the stomach, and these events spread around the circumference and down the stomach to the pylorus. A greater velocity of propagation around the stomach than down the stomach causes development of a ring of excitation, and this is the electrical basis underlying gastric peristaltic contractions. Studies have shown that electrical slow waves are generated by specialized pacemaker cells, known as interstitial cells of Cajal (ICCs). The main pacemaker ICCs in the stomach form a dense network of electrically coupled cells between the circular and longitudinal muscle layers of the corpus and antrum.

Brief History of Electrogastrography

During the first half of the twentieth century, before the availability of computerized literature searches, scientists who were working independently often discovered similar measures, phenomena, or relationships. The electrogastrogram (EGG) was discovered independently by at least three investigators: Walter Alvarez, a gastroenterologist; I. Harrison Tumpeer, a pediatrician; and R. C. Davis, a psychophysiologist. On October 14, 1921, after considerable experimentation with rabbits at the University of California in San Francisco, Walter Alvarez recorded the first human EGG. Figure 1.1 shows this EGG, which was recorded from an elderly woman with an abdominal wall hernia. The woman was so thin that Alvarez could observe gastric contractions of 3 min in the upper abdomen that corresponded to the 3cycles/min (cpm) electrical waves that are clearly seen in the EGG recording. Alvarez did not publish additional studies with the EGG during his long and productive career, probably because of the technical difficulties inherent in recording such a weak signal before the development of good vacuum tube amplifiers. I. Harrison Tumpeer, a pediatrician working at Michael Reese Hospital in Chicago, reported in 1926 that while he was attempting to record the EGG, “Alvarez of California published his results.” In a subsequent publication, Tumpeer successfully recorded the EGG from a 5-week-old child who had pyloric stenosis. Tumpeer and his coworkers selected this particular subject because they could observe gastric contractions by simply watching the surface of the skin over the abdomen. Figure 1.2 shows a portion of this EGG. Tumpeer described the EGG as looking like an electrocardiogram (EGG) with a slowly changing baseline. Tumpeer mentioned that cardiologists in 1926 often noted a changing baseline in EGG recordings that they could not explain. Thus, the EGG had been recorded, but perhaps not recognized as such, since the time of the first EGG at the turn of the twentieth century. Tumpeer used limb leads to record his EGG (not abdominal leads) because of his concern that each gastric contraction caused physical displacement of the skin over the child's abdomen. Subsequent studies showed that simultaneous recordings from limbs and abdomen are similar except that the amplitude of the EGG is greatly reduced from recordings from the limb leads.