ArticleLiterature Review

Current Concepts of the Antireflux Barrier

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Abstract

The lower esophageal sphincter, crural diaphragm, and phrenoesophageal ligament are the anatomic structures that constitute the antireflux barrier. The intraluminal pressure at the esophagogastric junction (EGJ) reflects the strength of the antireflux barrier. The end-expiratory pressure is a result of the tonic activity of the smooth muscles of the lower esophageal sphincter. The EGJ pressure increases during inspiration owing to the effect of the crural diaphragm. There is a reflex increase in the EGJ pressure during periods of increased intra-abdominal pressure, and the crural diaphragm contributes to this reflex contraction of the EGJ. Based on the contribution of the lower esophageal sphincter and crural diaphragm to the EGJ pressure, a two sphincter hypothesis of the antireflux barrier competence is suggested.

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... 86 La xerostomía crónica y el síndrome de Sjögren, por ejemplo, son condiciones en las que se encuentra alterado el depuramiento químico, y este mecanismo es una de las razones por las que estos pacientes presentan una predisposición a tener esofagitis. [87][88] El consumo de ciertos fármacos y la edad avanzada son otras causas frecuentes de xerostomía. 89 ...
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La fisiopatología de la enfermedad por reflujo gastroesofágico es multifactorial. Los eventos involucrados se inician en el estómago y, en forma ascendente, afectan la unión gastroesofágica y el esófago. Las características del material refluido impactarán en la magnitud del daño mucoso y en la percepción sintomática. Existen mecanismos defensivos y factores agresores, que son determinantes de la enfermedad. La intensidad con la que se perciben los síntomas es variable en cada individuo y está determinada por una combinación de mecanismos modulados por el sistema nervioso central y periférico, y factores psicológicos como la hipervigilancia. Las alteraciones en el aclaramiento esofágico junto con el tipo de material refluido probablemente sean los mayores determinantes para el desarrollo de una enfermedad de tipo erosiva, mientras que la sensibilidad de la mucosa lo sea para la percepción sintomática. El desarrollo de la enfermedad por reflujo gastroesofágico es el producto de un desbalance entre los factores mencionados anteriormente. Entender cuál es el mecanismo fisiopatológico predominante permite ofrecer al paciente el mejor tratamiento disponible.
... The swine's anatomy usually allows an easy insertion of catheters into the stomach. Other surgical models of GERD in the animals have been reported but all disrupted the EGJ anatomy or kept an indwelling catheter through the EGJ during experiments, adding potential bias on the assessment of ARB [15]. ...
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Article
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... GER is prevented by several anatomical mechanisms at the junction between the esophagus and stomach (Boeckxstaens, 2005;Castell, 1975;Hyun & Bak, 2011;Miller et al., 2007). Among them, the contribution of the lower esophageal sphincter (LES) is the most critical (Korn, Csendes, & Braghetto, 2011;Miller et al., 2007;Mittal, 1990;Patti, Gantert, & Way, 1997). The LES is regulated by at least two systems, one of which is the parasympathetic nervous system (including the vagus nerve; Boeckxstaens, 2005;Castell, 1975;Korn et al., 2011;Mittal & Balaban, 1997;Patti et al., 1997). ...
Article
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... We did not observe any patient swallowing during this study, and the timing of measurements make it unlikely that this mechanism caused the reduction in LOS pressure. In contrast, sustained distension of the oesophagus by balloon induces prolonged relaxation of the LOS [17], and it may be that distension of the pharynx by the inflated LMA cuff similarly reduces the LOS barrier pressure. ...
Article
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Article
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We studied gastro-oesophageal reflux (GOR) with a face mask and laryngeal mask airway (LMA), and the effects of inflation pressure and volume of the LMA cuff on oesophageal pH, in 60 patients. Patients were managed with either a face mask (group I) or LMA inflated to obtain a seal in the anaesthesia circuit at 7 cm H2O (group II) or 15 cm H2O (group III). A pH-sensitive probe with two electrodes, 10 cm apart, was placed in the oesophagus during anaesthesia and recordings were made continuously until patients awakened. There was a significant difference in the incidence of GOR between the face mask (group I) and the LMA (groups II-III) (P < 0.05) in the lower oesophagus but there was no difference in the mid-oesophagus. No correlation was found between pressure and volume inside the cuff and variations in oesophageal pH. We conclude that LMA use was associated with increased reflux in the low oesophagus but oesophageal pH was not influenced by variations in pressure or volume inside the LMA cuff.
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Article
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Excess alcohol consumption has been associated with multiple pathologies of the gastrointestinal tract. The consumption of large amounts of alcohol (hazardous drinking) facilitates acid regurgitation by reducing the pressure of the lower oesophageal sphincter and slowing both oesophageal motility and gastric emptying. Regardless of the type of alcoholic beverage involved lower alcohol doses also have been shown to induce decreased pressure in lower oesophageal, decrease in oesophageal motility and enhanced risk of gastroesophageal reflux disease (GERD). GERD can be important risk factor for oesophageal adenocarcinoma. For identification of hazardous drinking patients we can use AUDIT (Alcohol Use Disorder Identification Test). AUDIT has been created by World Health Organization experts as a simple screening test looking for hazardous drinking people.
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The presence or absence of a lower esophageal sphincter (LES) has been a matter of debate. The aim of the present study was to revisit the gastro-esophageal region in an attempt to elucidate further the presence or absence of such a structure. The distal part of the esophagus was investigated in 12 fixed and 2 fresh cadavers with the aid of a dissecting microscope. Our findings demonstrated a clear thickening of the circular muscle layer of the gastro-esophageal region in all specimens. The mean length of this muscular thickening was measured to be 3.1 cm. The thickest part of this segment was at its midsection. This midpart had a mean thickness of 5.4 mm. The thickness of the esophagus immediately superior to the sphincter had a mean of 2.7 mm. We believe that the findings of the present study strongly suggest the presence of an internal esophageal sphincter in the distal esophagus. Physiologic experimentation would now be necessary to verify our morphological findings.
Article
Esophagogastric junction (EGJ) pressure is the major barrier to gastroesophageal reflux. Recent studies suggest that contraction of the crural diaphragm increases esophagogastric junction pressure. Whether this increase in EGJ pressure is important in the prevention of gastroesophageal reflux is not known. Our aim in this study was to determine the effects of crural myotomy on the occurrence of gastroesophageal reflux. The spontaneous and stress gastroesophageal reflux before and after a surgical crural myotomy in four cats was studied. Spontaneous gastroesophageal reflux was recorded in the awake cats through a pH probe, placed via an esophagostomy, for periods of 12-24 hours. Stress reflux was studied during periods of airway obstruction and abdominal compression in anesthetized animals using the technique of simultaneous esophageal manometry and pH monitoring. There was a significant increase in the frequency of spontaneous acid reflux after crural myotomy. In anesthetized animals, there was an increase in the EGJ pressure during airway obstruction, which was abolished by a crural myotomy. Abdominal compression caused a reflex contraction at the EGJ that was not affected by crural myotomy. The crural myotomy resulted in a significant increase in the frequency of acid reflux during airway obstruction but not during abdominal compression. It is concluded that the crural diaphragm is important in the prevention of gastroesophageal reflux and its dysfunction leads to an increased incidence of gastroesophageal reflux.
Chapter
The primary purpose of the esophagus is to transport food from the mouth to the stomach; the esophagus has no digestive or absorptive function. The esophagus is a muscular tube that starts at the inferior border of the cricoid cartilage in the neck and traverses the chest, ending as it enters the stomach in the upper abdomen. While the esophagus seems like a simple organ at first glance, esophageal surgeons must be familiar with the complex anatomy and function of the upper and lower esophageal sphincters, the extensive lymphatic and vascular submucosal networks, and the clinical importance of the relationship of the esophagus with surrounding structures in all three areas of the body for effective surgical planning and the prevention of potential complications.
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Objectives: To characterize esophageal motility and esophago-gastric junction (EGJ) function in infants who underwent repair of an isolated congenital diaphragmatic hernia (iCDH). Methods: High Resolution Manometry with impedance was used to investigate esophageal motility and EGJ function after diaphragmatic repair in 12 infants with iCDH (11 left-sided; 9 patch repair). They had esophageal motility studies during neonatal admission (n = 12), at 6 months (n = 10) and at 12 months of life (n = 7). Swallows were analyzed using conventional esophageal pressure topography and pressure-flow analysis and were compared with 11 healthy preterm born infants at near-term age. Results: Esophageal peristaltic motor patterns in iCDH patients were comparable to controls. EGJ end-expiratory pressure was higher in patients with patch repair versus controls (p = 0.050) and those without patch (p = 0.009). The difference between inspiratory and expiratory pressures at the EGJ was lower in iCDH patients with patch (p = 0.045) compared to patients without. iCDH patients with patch showed increased Pressure Flow Index (PFI), resistance of bolus flow at the EGJ, compared to controls (p = 0.043). Conclusions: Normal esophageal wave patterns are present in the investigated patients with iCDH. EGJ end-expiratory pressure seems lower in iCDH patients without patch suggesting a decreased EGJ barrier function hence increased vulnerability to gastro-esophageal reflux. Patch repair appears to increase end-expiratory pressure at the EGJ above that of controls suggesting that patch surgery tightens the EGJ, thereby increasing flow resistance. This is in line with the increased PFI. In infants with a patch, the inspiration-expiration pressure difference is lower, reflecting diminished activity of the crural diaphragm.
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Chapter
Gastroesophageal reflux disease (GERD), the most common disorder of the esophagus, is extremely variable in its presentations and clinical course. It is known from epidemiological studies that many people complain of typical reflux symptoms, including heartburn and regurgitation, but only few request medical investigation. About 20%–40% of the world’s population has symptoms suggestive of GERD; an exact estimate is difficult because of the way the disease presents [1]. In 1985, Castell [2] described GERD as an iceberg, with a large base indicating patients with slight and episodic symptoms without need of medical assistance, a smaller portion of patients with moderate and recurrent symptoms and, at the top, patients with severe and persistent symptoms requiring special care (Fig. 1). Furthermore, a number of patients with atypical symptoms, such as refractory asthma, recurrent hoarseness, chronic unexplained cough or non-cardiac chest pain, are later discovered as having GERD. Thus, it seems evident that this disease is frequently underdiagnosed.
Chapter
The gastroesophageal junction is an area of great anatomical and functional complexity whose role is to restrict physiological gastroesophageal reflux (GER) (Fig. 1). “Restricting” is the operative word inasmuch as reflux is, within certain limits, a totally physiological phenomenon. In fact, GER is assisted by the gradient between the positive pressure of the stomach (10–20 mm Hg) and the pressure of the esophagus which, as a result of intrapleural pressure, is almost always negative (ranging from 0 to −10 mm Hg). Furthermore, certain movements (e.g. inspiring, bending forward, straining, coughing) cause a marked increase in abdominal pressure. For this reason food present in the stomach would constantly rise back up into the esophagus were it not for the intervention of competence mechanisms — competence being defined as the ability to restrict and contain the incidence of gastroesophageal refluxes.
Chapter
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Role of the Stomach in the Antireflux Barrier and Gastroesophageal Reflux Pathogenesis The gastroesophageal antireflux barrier in humans depends on the interaction of three components: a valvular mechanism, the lower esophageal sphincter (LES); a propulsive “pump“, the esophagus; and a reservoir, the stomach [12,38,39,50,95] (Fig. 1). Although the controversial issues concerning the valvular mechanism, such as the real existence and role of an anatomic sphincter [41,95], a well-functioning gastric reservoir would certainly be crucial for the efficacy of the antireflux barrier. In the presence of an incompetent LES, the stomach can contribute to gastroesophageal reflux (GER) by providing aggressive fluid to reflux, but it can also challenge directly the LES. The stomach may induce episodes of reflux if the intraluminal pressure overrides the LES pressure. Gastric distension can produce an incompetent valve by the shortening of the LES length or by inducing transient LES relaxations, as has been demonstrated in both healthy volunteers and patients [30, 33,50,70,79,108,113]. Thus, gastric emptying dysfunction could conceivably play an important role in GER by intensifying these mechanisms [69,103,112].
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Incompetent cardia (IC) or loose cardia is not uncommon at endoscopic examination but its meaning is not clear. Such incompetence could facilitate gastroesophageal reflux and the appearance of esophagitis as a consequence. The aim of this study is to investigate if there is an association between IC and reflux esophagitis (RE). A review was made of 395 consecutive endoscopic reports of adult males and females performed at the Botucatu Clinics Hospital, of the Unesp - University of the State of São Paulo. Diagnosis of IC is defined by the endoscopic image in which the cardia is partially opened and/or involves the endoscope in a loose manner. Esophagitis characterization was based in the Los Angeles classification. The statistical analysis showed a significant association between CI and RE (p < 0.0001). Although there is not a clear explanation for this association, some hypotheses could be suggested involving hypotonic LES, diaphragmatic crura ineffectiveness and TLESR disorders as conditions able not only to keep the cardia relaxed but also to the reflux followed by esophagitis.
Article
Se analiza la repercusión clínica, manométrica, pH-métrica e isotópica a largo plazo en el tratamiento quirúrgico de la enfermedad por reflujo gastroesofágico, en un grupo de 26 pacientes tratados mediante la implantación de una prótesis de silicona en la unión esofago-gástrica por vía abdominal. Se valora la evolución de las repercusiones motoras, estáticas y dinámicas, de los parámetros manométricos en ambos esfínteres, superior e inferior, y en el cuerpo esofágico, mediante tres evaluaciones al año, tres años y una última entre seis y diez años. La media de seguimiento es de 119 meses. En la última evaluación, se incorporan determinaciones pH-métricas, mediante pH-metría ambulatoria de 24 horas y un estudio isotópico con radionúclidos para determinar el aclaramiento esofágico de líquidos a largo plazo. Las conclusiones obtenidas son de un buen control de la enfermedad y de estabilidad en las mejoras manométricas producidas en los parámetros de EEI y del cuerpo esofágico. Las complicaciones postoperatorias son del 15%
Article
High-resolution manometry (HRM) is a new technique to investigate the motor function of the esophagus. It differs from conventional manometry in recording pressures by solid state microtransducers at 12 points around the circumference at every centimeter of esophageal length, and displaying the data in pseudo-three-dimensional format using a topographic plot, where esophageal pressures within a given range are represented by different colors. The large amount of data and the capacity to analyze and display it intuitively has afforded many new insights into esophageal dysfunction. Among these insights are the ability to distinguish three different subtypes of achalasia and predict their response to therapy, better understanding of the relationship between the lower esophageal sphincter (LES) and the crural diaphragm, the development of novel quantitative parameters to understand the nature of the dysfunction in non-specific esophageal motor disorders, and the elucidation of a newly described motility disorder characterized by failure of peristalsis at the transitional zone between the upper skeletal muscle and the more distal smooth muscle portion of the esophagus. It is also ideally suited to analysis of the effect of prokinetic medications. The method is quicker and less uncomfortable for patients and the analysis is visually appealing and intuitively comprehensible. Despite these potential advantages, there are currently no data to demonstrate a clinical advantage in treatment. The results of such studies will be crucial to the acceptance of this novel technology.
Article
Swallowing sounds can be heard in the lower esophagus by xiphoid auscultation. We hypothesize that the xiphoid sound analysis could provide information concerning the integrity of the esophagogastric junction (EGJ), i.e., superposition of the lower esophageal sphincter (LES) and the diaphragm to assess clinical diagnosis of gastroesophageal reflux disease (GERD) and results of Nissen fundoplication (NF). The aim was to evaluate the changes in sound parameters using our acoustic technique after reorganization of the EGJ after NF. For 21 patients with GERD and hiatus hernia, two microphones were placed below the cricoid and on the xiphoid cartilages. The frequency and duration of xiphoid sounds, esophageal transit time were calculated. We defined the xiphoid sound as composed of vibration groups separated by periods >100 ms. The number of vibration groups, number of vibrations per group, and interval between groups were also calculated. The xiphoid sound frequency was increased after NF, and the esophageal transit time and xiphoid sound duration were significantly decreased. A significant correlation was found between xiphoid sound duration and LES-diaphragm displacement. The number of vibration groups and interval between groups were reduced after NF. The acoustic technique for swallowing revealed the effects of NF upon the dynamic profile of the EGJ. The organization of vibration groups at the EGJ suggested that the passage of the bolus was modified by hiatus hernia, i.e., dissociation between the LES and the diaphragm and regularized by NF. Concomitant acoustic and radiologic study should contribute to better understanding of sound related to EGJ structure and boli.
Article
Esophageal pH-metry is the test of choice for diagnosing gastroesophageal reflux. However, although it allows acid refluxes to be distinguished, it is of limited value for identifying alkaline or mixed (acid mixed with alkaline material) refluxes. To evaluate the ability of dual pH-metry to identify alkaline or mixed refluxes, the gastric acidity and gastroesophageal reflux pattern were evaluated simultaneously in 64 patients with mild-moderate esophagitis, in 28 patients with severe or complicated esophagitis, and in 20 healthy subjects. A dual esophageal gastric pH-probe allowed three different types of esophageal reflux to be distinguished: (a) acid refluxes, defined as a drop in esophageal pH to values less than 4 together with a gastric pH less than 4; (b) mixed refluxes, defined as a drop in esophageal pH from baseline to values greater than 4 associated with rises in gastric pH to greater than 4 values; (c) alkaline refluxes, defined as a rise in esophageal pH to greater than 7 associated with a simultaneous increase in gastric pH to greater than 4. Gastric acidity was more significantly reduced in patients with severe or complicated esophagitis than it was in healthy subjects (P less than 0.01). The reflux pattern in both mild-moderate and severe esophagitis was characterized by mainly acid refluxes and a marked increase in the time the esophagus mucosa was exposed to acid (P less than 0.001). Pure alkaline refluxes were rare (less than 1%) in both healthy subjects and esophagitis patients. The number of mixed refluxes was considerably higher in severe esophagitis patients than it was in either mild-moderate esophagitis patients or controls (P less than 0.05). The finding of mixed refluxes in severe or complicated esophagitis suggests that biliary acids and/or pancreatic enzymes are involved in the pathogenesis of severe forms of esophagitis.
Article
Much has been learned about the pathophysiology of gastro-esophageal reflux (GER) since it was initially described by Asher Winkelstein in 1935. With the development and refinement of esophageal function tests in the past decades, the diagnostic modalities have become available for a deliberate and systematic evaluation of antireflux mechanisms. Some of the newer concepts of the pathogenesis of reflux esophagitis are reviewed in this article.
Article
Gastro-oesophageal reflux disease (GORD) ranges from episodic symptomatic reflux without oesophagitis to severe oesophageal mucosal damage, such as Barrett’s metaplasia or peptic stricture. The multifactorial pathogenesis of GORD prevents medical cure of the disease. GORD is a chronic disease with a high tendency to relapse, requiring a long term treatment strategy in practically all patients. Complete healing of all mucosal lesions is not necessarily the aim of treatment in all patients. In milder forms of reflux disease, symptom relief is the most important goal. Many patients with mild GORD do well on symptomatic self-care with antacids and/or alginate. In addition, lifestyle changes should be advised to all patients: these improve symptoms and enhance the efficacy of therapy. In the acute treatment of GORD the prokinetic drug cisapride has been shown to be effective in relieving symptoms and healing grade I to II oesophagitis. Cisapride decreases symptomatic and endoscopic relapse in patients with mild GORD. Histamine H2-receptor antagonists are effective in relieving reflux symptoms in about 50% of patients, but with regard to healing, H2-antagonists appear to be mainly effective in grades I and II and not in higher grades of oesophagitis. Maintenance treatment with H2-antagonists is mainly symptomatically effective in patients with mild GORD. Proton pump inhibitors (PPIs) provide significantly higher healing rates of reflux oesophagitis than H2-antagonists, even in the more severe cases of oesophagitis and Barrett’s ulcers. PPIs are also effective in patients with oesophagitis refractory to treatment with H2-antagonists. PPIs have become the drugs of first choice in healing of all patients with more severe forms of reflux oesophagitis, and increasingly also for patients with milder forms of oesophagitis, certainly those who fail to respond to other drugs. In maintenance treatment of GORD, PPIs are the most effective drugs, offering the possibility of keeping nearly all patients in remission with adjusted doses. Current patient data of up to 5 years indicate the safety of this strategy for this period, but the exact consequences of strong acid inhibition over a longer period still have to be clarified. At present, all but a few patients with GORD can be managed adequately by medical therapy.
Article
The phrenico-esophageal ligament (PEL), which is claimed by some to be an important anti-reflux barrier, has been accepted as an important structure by some surgeons dealing with the surgical treatment of hiatal hernias. However, the characteristics of its anatomical structure and the physiological importance of this ligament is still a subject of discussion. The aim of this study was to define this anatomic structure and to point out the clinical importance of the PEL. This study has been carried out on samples taken from 2 fresh and 12 fixed cadavers. The PEL was observed to be derived from the transversalis and endothoracic fascia attaching the esophagus to the diaphragmatic crura at the region of the esophageal hiatus. While the transversalis fascia covered the inferior surface of the diaphragm, it was observed to divide into upper and lower leaflets when it approached the esophageal hiatus. The endothoracic fascia turned superiorly at the level of esophageal hiatus and attached on to the esophagus by uniting with the upper leaflet of the transversalis fascia in 11 of the specimens. In three of the specimens, it attached on the esophagus at a higher level than the transversalis fascia. The histologic sections of our study revealed that the PEL is formed by collagen and elastic fibers composed of fibroblasts and blood vessels. Since the PEL is a strong structure that firmly attached to the esophageal wall and surrounded the upper part of the distal esophagus like a skirt, it is reasonable that it may play an important role in the gastroesophageal sphincteric mechanism. Histological evidence for decrease in collagen fibers with age and the loose arrangement of the elastic fibers due to this decrement might decrease the resistance and the elasticity of the PEL. This situation may explain the predisposition to hiatal hernias seen with increased in age.
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Studies were performed in anesthetized opossums to determine the influence of binding of circulating gastrin with a high titer gastrin antiserum on lower esophageal sphincter pressure. Gastrin antiserum or control antiserum was administered intravenously in successive doses of 0.02, 0.1, and 0.5 ml/kg on separate days. The lower esophageal sphincter pressures were measured for 1 h before and for 1 h after antiserum administration. The control serum caused no binding of opossum circulating gastrin, nor did it modify lower esophageal sphincter pressure. On the other hand, the administration of gastrin antiserum resulted in the binding of 85-90% of circulating gastrin, but it did not reduce sphincter pressure. A continuous infusion of 0.25 mug-kg-1-h-1 of synthetic human gastrin I caused a significant (P less than 0.05) increase in the sphincter pressure, a 30-fold increase in gastric acid output, and a fourfold increase in immunoreactive gastrin in the opossum blood. Prior treatment with 0.1 ml/kg of gastrin antiserum antagonized and 0.2 ml/kg of the antiserum abolished the gastrin-stimulated gastric acid secretion and the stimulating effect of gastrin on lower esophageal sphincter pressure. However, neither dose of antiserum modified basal lower esophageal sphincter pressure. It is concluded that circulating gastrin may be an important determinant of basal sphincter pressure.
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Currently it is believed that lower esophageal sphincter closure is maintained by tonic neurohormonal activity. Studies were performed to evaluate the role of neural and myogenic activity in the genesis of resting sphincter pressure in the opossum. The neural activity in the sphincter was blocked by intravenous administration of the puffer fish poison, tetrodotoxin, in intact animals. The respiration in these animals was assisted with a respirator, their blood pressure was supported by intravenous administration of Ringer's solution, and their body temperature was maintained by heating lamp. The lower esophageal sphincter pressures were measured with water-filled and continuously perfused catheters which were anchored to the lower esophageal sphincter using a new technique. Tetrodotoxin blocked the sphincter response to neural stimulation with vagal stimulation, esophageal distention, and local electrical stimulation of the sphincter. The mean resting sphincter pressure before tetrodotoxin was 59.0 +/- 2.6 mm Hg, and it was 64.4 +/- 6.9 mm Hg after tetrodotoxin (P greater than 0.05). During neural block with tetrodotoxin, the sphincter response to administration of isoproterenol or bethanechol was similar to that during the control period (P greater than 0.05). These studies show that: (1) Tetrodotoxin can be administered in intact animals to achieve complete block of neural activity in the lower esophageal sphincter; (2) sphincter muscle is not adversely affected by tetrodotoxin; and (3) block of neural activity does not alter the resting lower esophageal sphincter pressure.
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We performed studies in the opossum to define the influence of the vagi in the control of lower esophageal sphincter (LES) function. Bilateral vagotomy caused transient sphincter hypertension which was prevented by phentolamine and by atropine. Stimulation of the peripheral end of vagus, after bilateral cervical vagotomy, caused relaxation of the LES over a wide range of frequency and intensity of electrical stimulation. The relaxation was less marked at the lower frequencies of stimulation, and atropine treatment did not enhance this relaxation. In other experiments, atropine treatment reversed the rise in gastric (fundic) pressure with the vagal stimulation, but atropine did not enhance the degree of LES relaxation. Stimulation of the central end of the vagus caused an increase in LES pressure due to a centrally mediated reflex; the efferents for this motor response were not present in the vagi, as the reflex contraction persisted after bilateral vagotomy. The LES contraction with the stimulation of the vagal afferents was antagonized by phentolamine as well as by atropine. These studies suggest that: (a) the vagi do not mediate any cholinergic excitatory influences to the LES and the vagal influence of the sphincter is entirely inhibitory; (b) the vagi carry afferent fibres for a centrally mediated neural reflex which contracts the LES, but the efferent path of this reflex arc does not lie in the vagi.
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In opossums, cats, and monkeys comparisons were made of length resting tension relationships and responses to low frequency electrical field stimulation among serial 2 mm wide strips cut transversely from the esophagogastric junction and adjacent stomach and esophageal body. Three regions could be distinguished on the basis of the nature of the response to field stimulation. Strips from the stomach contracted during stimulation; those from the esophageal body contracted briefly after the end of the stimulus; strips from the esophagogastric junction relaxed during stimulation. Transitional areas lay between the three regions showing these tetrodotoxin sensitive responses. The length resting tension slopes of strips from the esophagogastric junction were steeper than those of strips from the stomach and esophageal body. The strips which relaxed with field stimulation included those with the steepest slopes of the length resting tension relationship. Slopes of length resting tension were poorly correlated with muscle mass. In all three species, intrinsic specialization occurs at the esophagogastric junction in the nature of the innervation and in the mechanical properties of the inner muscle layer.
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The effect of rabbit vasoactive intestinal polypeptide (VIP) antiserum on in vitro relaxation of the lower esophageal sphincter (LES) was studied in 10 cats. The stomach and esophagus were opened along the lesser curvature of the stomach and stripped of mucosa. Consecutive strips were cut and mounted in a 2.5-ml muscle chamber. They were perfused with Tyrode's solution and oxygenated continuously. After equilibration for 1 h, perfusion was stopped and one strip from the lower esophageal sphincter region was incubated in solution that contained 12-25 parts of VIP antiserum per 1,000 to Tyrode's solution, while a second strip was incubated in a solution of normal rabbit serum at the same concentration. A third strip was maintained in Tyrode's solution for the duration of the experiment. After a 1-h incubation, the strips were stimulated with 6-s square wave trains of 0.1-, 0.2-, 0.4-, and 0.8-ms pulses at 1, 2, and 5 Hz. These stimulation parameters produced LES relaxation that was completely blocked by tetrodotoxin but not by atropine or phentolamine. The strips incubated in Tyrode's solution or in normal serum relaxed reliably and consistently at all levels of stimulation. In the antiserum-treated strips, LES relaxation in response to all stimuli was significantly inhibited. Strips treated with normal serum were relaxed in a dose-dependent fashion by 10(-7) and 10(-6) M VIP, whereas the antiserum inhibited the relaxation induced by 10(-7) M, but not by 10(-6) M, VIP. Stimulation with two successive 15-min trains of electrical pulses (2 ms, 5 Hz) separated by 30 min of rest released increasing amounts of VIP into the bathing solution. VIP released during the second train of electrical stimulation was significantly (P less than 0.05) greater than in control conditions. In the cat LES, VIP antiserum inhibits the relaxation induced by exogenous VIP or by electric stimulation of nonadrenergic, noncholinergic inhibitory nerves at a level that causes the release of VIP. These findings are consistent with the hypothesis that VIP may be an inhibitory neurotransmitter responsible for LES relaxation.
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Silver-impregnated stretch preparations of the opossum esophageal body and lower esophageal sphincter were compared as to the general aspect of the plexus, density of perikarya and ganglia, type and size of ganglia, nerve bundle diameter, density of nerve bundle intersections, and relations between ganglia and nerve bundle intersections. Density of perikarya and ganglia, but not density of nerve bundle intersections, declined along the esophagus, with a nadir at the sphincter. The proximal body contained 960-1358 perikarya/cm2 and the sphincter, 70-333 perikarya/cm2. Ganglia contained 3-100 cells, 54% having less than 10. Many small ganglia lay outside nerve bundles (parafascicular ganglia), the proportion being greatest in the sphincter (25%-54%). Many ganglia (15%-22%) were remote from nerve bundle intersections and many intersections were remote from ganglia, 28%-35% in the body and 66%-69% in the sphincter. Nerve bundle diameter was a single population with a skewed distribution; the mode was about 0.1 mm.
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We investigated the mechanism of gastroesophageal reflux (GER) in 10 health volunteer subjects. Continuous recordings of intraluminal esophageal pH and pressure were obtained on two consecutive nights from 6:00 p.m. to 6:30 a.m. in each subject. During each study, the subject remained recumbent, except to eat a standardized meal after 1 h of basal recording. A manometric assembly with seven recording lumens monitored: (a) lower esophageal sphincter (LES) pressure via a sleeve device 6.5 cm in length, (b) esophageal-body motor activity, (c) swallowing activity in the pharynx, and (d) gastric pressure. An electrode 5 cm above the LES recorded esophageal pH. Sleep was monitored by electroencephalogram. All subjects showed wide variations of basal LES pressure. GER was not related to low steady-state basal LES pressure, but rather occurred during transient 5-30 s episodes of inappropriate complete LES relaxation. The inappropriate LES relaxations were usually either spontaneous or immediately followed appropriate sphincter relaxation induced by swallowing. The majority of GER episodes occurred within the first 3 h after eating. During the night LES relaxation and GER occurred only during transient arousals from sleep or when the subjects were fully awake, but not during stable sleep. After GER the esophagus was generally cleared of refluxed acid by primary peristalsis and less frequently by secondary peristalsis. Nonperistaltic contractions were less effective than peristalsis for clearing acid from the esophagus. We conclude that in asymptomatic recumbent subjects GER is related to transient inappropriate LES relaxations rather than to low steady-state basal LES pressure and also, that primary perstalsis is the major mechanism that clears the esophagus of refluxed material.
Article
To determine the role of the diaphragm in the genesis of the high-pressure zone at the lower esophageal sphincter (LES) we studied the effect of diaphragmatic contraction on lower esophageal sphincter pressure in 10 anesthetized adult cats. Despite anchoring the pressure recording assembly within the LES to prevent axial movement of the sphincter during respiration relative to the pressure recording ports, there was an average oscillation in LES pressure of 17.4 ± 5.5 mmHg, the frequency of which was the same as the respiratory rate. Peak LES pressure occurred at end-inspiration corresponding with peak diaphragmatic electromyogram. During periods of central apnea induced by manual hyperventilation there was absence of both diaphragmatic electromyogram and the oscillations in LES pressure. Lower esophageal sphincter pressure during apnea was equal to end-expiratory pressure during spontaneous respiration. Following complete neuromuscular blockade with pancuronium, artificial respiration with increasing tidal volumes resulted in increasing oscillations in pressure. However, the magnitude of the pressure oscillation even at tidal volumes four times normal was always significantly below that observed during spontaneous eupnic respiration. Furthermore, progressive augmentation of diaphragmatic electromyogram activity by breathing 5% CO2 in air revealed a linear correlation between the magnitude of the respiratory-induced pressure oscillations of the LES and peak integrated diaphragmatic electromyogram in individual animals. It is concluded, therefore, that (a) intrinsic LES tone is best approximated by end-expiratory pressure during spontaneous respiration, (b) the respiratory-induced oscillations in LES pressure are primarily the result of active diaphragmatic contraction, and (c) the level of diaphragmatic electrical activity directly influences the magnitude of the pressure oscillation.
Article
The authors report an anatomical, morphological and functional study on the diaphragmatic passage of the esophagus. This study allows to conclude that the anatomical structures of the region play an important role in gastroesophageal continence. The idea of physiological sphincter must be broadened and take into account the crura of the diaphragm which from a true extrinsic anatomic sphincter. The authors also insist on the dynamic aspect of this region and on the variations of pressure related to the respiratory movements. From a practical standpoint, the conclusions of this study should permit the surgeon to make a dynamic investigation of gastroesophageal reflux and adapt treatment to a more precise physiopathological mechanism.Les auteurs rapportent un travail anatomique, morphologique et fonctionnel, sur la traverse diaphragmatique de l'sophage. Cette tude leur permet de conclure que la place rserve aux structures anatomiques dans la continence gastro-sophagienne est importante. La notion de sphincter physiologique doit tre largie en tenant compte des piliers du diaphragme qui forment un vritable sphincter anatomique extrinsque. Ils insistent sur l'aspect dynamique de cette rgion et sur les variations de pression en relation avec les mouvements respiratoires. Dans la pratique les conclusions de ce travail devraient permettre au chirurgien de faire une exploration dynamique du reflux gastro-sophagien et d'adapter son geste un mcanisme physiopathologique prcis.
Article
In order to measure muscle thickness and to define the muscular architecture at the gastroesophageal function, both en bloc fixation and a new method of preparing dried fiber specimens were used. Specimens were obtained from 32 kidney donors and human cadavers. Wall thickness was measured at 32 identical locations in the esophagus and stomach. The oblique gastroesophageal ring (GER) was the site of greatest muscular thickness and served as a reference point. From the GER the muscle thickness tapered (P less than 0.05 to P less than 0.001) in both a cephalic (esophageal) and caudal (gastric) direction for a length of 31 mm +/- 2.5 SD. The increase in thickness was due to an increase in the muscle mass (fiber aggregation) of the inner muscle coat. The muscle bundles of this coat split up 10.2 mm +/- 3.0 SD above the GER (fixed specimen) and for a length of 25 mm +/- 8 SD formed short transverse muscle clasps on the lesser curve side. Those muscle bundles on the greater curve side formed long oblique gastric fiber loops. The angle of His was inconstant in location and distal to the uppermost gastric oblique fibers (18 mm +/- 7 SD) and to the GER (9 mm +/- 6 SD).
Article
Studies were performed in the opossum to evaluate the morphological characteristics of the lower esophageal sphincter. The sphincter and the esophageal body were identified manometrically and fixed in situ by perfusion with aldehyde fixative. Light microscopy revealed that: (1) longitudinal muscle layers of the sphincter and the esophageal body were similar in thickness and compactness, and (2) circular muscle of the sphincter was thicker and was composed of muscle fasciculi with abundant intervening connective tissue as compared to the compact muscle fasciculi of the circular muscle of the esophageal body. Electron microscopy showed the circular muscle fibers of the sphincter to have irregular protuberances from their surfaces, whereas the circular muscle fibers of the esophageal body possessed smooth surfaces. Several types of junctional complexes between adjacent muscle fibers were observed; however, there was no difference in their distribution in the sphincter or esophageal body. The majority of the nerve varicosities contained a mixture of agranular (350 to 450 A) and large dense core vesicles (800 to 1600 A); varicosities containing small granular vesicles were not found in any area of the esophagus. When varicosities were cut along the longitudinal axis of the axon, they often showed grouping of similar vesicle types in different areas along the axon varicosities. There was no difference in the type of varicosities found in the sphincter or the esophageal body. These studies show that: (1) circular muscle of the sphincter can be morphologically distinguished from that of the esophageal body; (2) there is no difference in the morphology of the nerve terminals or the vesicle types in the two areas; and (3) classification of the varicosities based upon the predominance of the vesicle types may be artifactual because of sampling error.
Article
The author who has worked out an experimental radiological method of study of the physiology of the oesophagus by means of a non-surgical implantation of tantallium in the oesophageal walls of the cat, publishes the results of his own researches and those of his collaborators with regard to the physiology of the oesophageal dynamics, the lower oesophageal sphincter, oesophagitis from reflux, hiatal and sliding hernia, and oesophageal manometry. Attention is called to 1) the role, neglected until today, of the longitudinal musculature of the oesophagus, the contractions of which shorten the organ, so pushing the bolus on towards the stomach and contributing to the opening mechanism of the lower oesophageal sphincter; 2) and to the fact that normally, during the oesophageal peristalsis the stomach herniates into the thorax by 1 to 2 centimeters; 3) furthermore the tonus of the inferior oesophageal sphincter is an intrinsic, myogenic property of the sphincter itself whereas the gastrin and the vagus are of little importance in its genesis. With regard to oesophagitis of the so-called reflux variety, in only 40% of the patients was a true reflux found radiologically. On the contrary a hiatal hernia was often present. A hiatal hernia is easily diagnosed radiologically and, in the present state of knowledge it is still not possible to formulate any pathogenetic relation as between it and reflux oeseophagitis. Finally the author defines the conditions and methods that are indispensable for obtaining reliable data from manometric study of the oesophagus. The results of the study by the author reveal a correlation of 95% between fluoroscopy and manometry in what concerns the study of the quality of the oesophageal peristalsis, which is equivalent to saying that if the peristalsis is normal on fluoroscopy it is also normal on manometry. Nevertheless, manometry in clinical practice is necessary solely for the quantitative measurement of the amplitude of the peristaltic pressure and of the force of the sphincteric closure. The author considers that, with regard to the future, the following points must be clarified: the physiopathology of reflux oesophagitis, the mechanism of the contraction of the oesophageal musculature, the neural control of the peristalsis, and the neurotransmissions that govern the relaxation of the lower sphincter of the esophagus.
Article
Since the original observations by Von Euler and Gaddum, considerable interest has developed regarding the role of substance P in smooth muscle function. The purpose of the present investigation was to evaluate the effect of intravenously administered substance P on the vivo motor function of the lower esophageal sphincter (LES). Intraesophageal pressures were monitored by an assembly of polyvinyl catheters attached to pressure transducers and a recorder. The catheters were continuously perfused with bubble-free water. Administration of 5, 10, 25, 50, and 100 ng per kg of substance P stimulated the LES, respectively, 16, 32, 57, 147, and 169% above control values. Tetrodotoxin, phentolamine, hexamethonium, methysergide, and bilateral cervical vagotomy did not alter the response of the LES to substance P. Atropine in 40-, 250-, and 500-microgram per kg doses significantly but partially inhibited the response of the LES to substance P. It is concluded that subtance P is a potent stimulant of the LES. The stimulatory effect of substance P may involve both cholinergic muscarinic and noncholinergic mechanisms. It is conceivable that substance P may be a modulator of LES pressure, although the exact physiological significance is not clear at the present time.
Article
The use of a constantly perfused side hole sensor (CPSH) for continuous measurement of maximal lower esophageal sphincter pressure (LESP) is associated with important but variable undermeasurement as a result of side hole displacement. A 5 cm long pressure sensor has been developed which measures maximal LESP continuously in the face of movement of the sphincter within the sensor length. This sensor, the perfused sleeve, is described, and validated by comparison with CPSH in man, the dog, and a model esophageal sphincter. The sleeve detects maximal LESP accurately, regardless of sphincter length, over the pressure range encountered in the lower esophageal sphincter. Continuous recording of LESP with the sleeve is unaffected by displacement that causes serious undermeasurement with CPSH.
Article
I studied the esophagogastric junction in fresh and preserved cadaveric specimens in the infant, adolescent and adult as well as by reverse gastroesophagoscopy, both intraoperatively and postoperatively, on unanesthetized patients. Cut sections of fresh specimens of the lower esophagus consistently showed an increased thickness of the lower 2-3 cm of the inner circular muscle layer of the esophagus. The layers are more firmly fused at this level and a color change is evident. From the serosal surface, a slight whitish indenture marks this area. From the mucosal surface, this area is the level of the transition zone. This is the lower esophageal sphincter. Reverse gastroscopy performed via a mature gastrostomy enabled me to identify and photograph a diaphragmatic sphincter and a lower esophageal sphincter.
Article
Smooth muscle strips representing longitudinal and circular muscle layers of the esophagogastric junction (EGJ) and esophageal body (EB) of the human esophagus were prepared. The strips were mounted in organ baths and isometric tension was recorded. Square wave stimulation was applied through platinum electrodes. Only responses abolished by tetrodotoxin (TTX) were considered neurogenic. Strips taken from longitudinal muscle layers of the EB and EGJ contracted during field stimulation. The responses evoked were abolished by atropine, and optimal frequency of stimulation was 40 Hz. In strips taken from the circular muscle layer of the EB, a contraction occurred after cessation of the stimulus. Atropine inhibited 90% of this response; the optimal stimulation frequency was 40 Hz. When a tone was induced in strips from this layer, a TTX-sensitive relaxation was seen during field stimulation. During stimulation of strips from the EGJ circular muscle layer, which was the only preparation developing spontaneous active tone, a relaxation was seen. A small contraction followed after termination of the stimulus. The relaxation, which was nonadrenergic, noncholinergic, reached maximum at 10 Hz. Atropine inhibited 40% of the contraction. The results suggest that in the longitudinal muscle layer of the human lower esophagus field stimulation causes postganglionic nerves to release transmitter(s) acting on muscarinic receptors. The responses of circular muscle layers seem to be mediated through release of at least two transmitters.
Article
Isolated smooth muscle strips from the human esophagus representing both the longitudinal and circular layers of the esophagogastric junction and the esophageal body were prepared. The strips were mounted in organ baths, and resting length was defined. By repeatedly increasing the length of the strips with 20% of resting length and recording values of resting and active tensions, length-tension relations for each muscle type were constructed. Only circular strips from the esophagogastric junction developed active, resting tension, disclosed by replacing the normal Ca2(+)-containing Krebs solution with Ca2(+)-free medium. Carbachol (10(-6) M) was used for submaximal activation of the contractile apparatus. At lengths between 180 and 260% of resting length, all strips reached optimum length (LO) where further elongation gave no further increase in active tension development. Repeated stimulations with carbachol was possible at a length of 200% of LO without affecting reproducibility. Determination of different collagen components revealed no differences between muscle types.
Article
We studied the effects of increased intra-abdominal pressure on the lower esophageal sphincter (LES) pressure in 15 healthy subjects. The role of the diaphragm in the genesis of LES pressure during increased intra-abdominal pressure was determined by measuring diaphragm electromyogram (EMG). The latter was recorded using bipolar intraesophageal platinum electrodes that were placed on the nonpressure sensing surface of the sleeve device. We also measured the LES pressure response to increased intra-abdominal pressure during inhibition of the smooth muscles of the LES by intravenous atropine (12 micrograms/kg). Straight-leg raising and abdominal compression were used to increase intra-abdominal pressure. Our results show that the increase in LES pressure during straight-leg raising is greater than the increase in gastric pressure. During abdominal compression, the rate of LES pressure increase is faster than that of the gastric pressure, suggesting an active contraction at the esophagogastric junction. The increase in LES pressure during periods of increased intra-abdominal pressure is associated with a tonic contraction of the crural diaphragm as demonstrated by EMG recording. Atropine inhibited the resting LES pressure by 50-70% in each subject but had no effect either on the peak LES pressure attained during increased intra-abdominal pressure or tonic crural diaphragm EMG. We conclude that 1) there is an active contraction at the esophagogastric junction during periods of increased intra-abdominal pressure and 2) tonic contraction of the crural diaphragm is a mechanism for this LES pressure response.
Article
We studied the effects of involuntary and voluntary contraction of the diaphragm on esophagogastric junction (EGJ) pressure during esophageal distension in healthy human volunteers. The EGJ pressure was monitored using a Dent sleeve device. Along with the pressure we concurrently monitored diaphragm electromyogram (EMG) using intra-esophageal bipolar electrodes that were placed on the nonpressure sensing surface of the sleeve device. Graded esophageal distensions were performed by graded inflations of a 2-cm-diameter balloon that was positioned 7 cm above the EGJ. The graded esophageal distensions caused a graded increase in the amplitude of lower esophageal sphincter (LES) relaxation (end-expiratory EGJ pressure). In a majority of the subjects, esophageal distension had no effect on spontaneous inspiratory EGJ pressure increase and diaphragm EMG. During sustained LES relaxation of greater than 70% induced by sustained esophageal distention, graded voluntary contractions of the diaphragm induced proportional increases in the EGJ pressure and diaphragm EMG. The EGJ pressure and diaphragm EMG were similar during diaphragmatic contraction both before and during esophageal distension. During a maximal and sustained diaphragm contraction, esophageal distension had no effect on the EGJ pressure. We conclude that there are two distinct sphincteric mechanisms at the EGJ, the LES and crural diaphragm, and they respond differently to distension of the distal esophagus.
Article
Single cells and whole tissue specimens were used in this study to determine sources of Ca2+ utilized for contraction of the circular muscle layer of esophagus and lower esophageal sphincter (LES) of the cat. In vitro circular muscle specimens from the cat esophagus respond to electrical stimulation with phasic contractions at the end of the stimulus, whereas the LES spontaneously maintains tonic contraction and relaxes during stimulation. In Ca2+-free buffer, esophageal contractions rapidly decline and disappear within 10 min after the removal of Ca2+, while LES tone is only partially reduced. Similarly, incubation in a solution containing the Ca2+ influx blocker, La3+, abolishes esophageal contraction but only partially decreases LES tone. Conversely, strontium and caffeine substantially reduce LES tone without affecting the amplitude of esophageal contractions. In single muscle cells isolated by enzymatic digestion from the LES and the body of the esophagus, blockade of extracellular Ca2+ influx by methoxyverapamil (D 600) or ethyleneglycol-bis-(beta-aminoethylether) N,N'-tetraacetic acid abolished esophageal contraction in response to acetylcholine without affecting LES cells, and conversely, strontium abolished LES contraction without affecting esophageal cells. These data are consistent with the view that extracellular Ca2+ is required to initiate esophageal phasic contraction, while the LES has the ability to utilize intracellular Ca2+ to maintain resting tone and to contract in response to acetylcholine.
Article
This study investigated sphincter-body differences in neuronal density and morphometry between the esophageal sphincter and body with a view to determining whether previously reported differences are authentic. The anatomical limits of the opossum lower esophageal sphincter were correlated with its physiological behavior by manometric demarcation. Following this, peeled whole mounts and paraffin and cryosections were used to study the morphology and morphometry of the esophageal myenteric plexus. Thirty animals were used and seven quantitated. The plexus of the esophageal body was located as usual in a plane between the longitudinal and circular muscle, which coincided with the plane of cleavage when these muscle layers were peeled apart for studying the plexus in whole mounts. In contrast, the plexus was located in several planes in the lower esophageal sphincter, which had no cleavage plane. Therefore, peeling the sphincter removes neurons and yields falsely low counts, making peel preparations of this region unsuitable for neuronal quantitation. In paraffin sections, the neuron density in the esophageal body 7 cm above the sphincter was 6,353 +/- 850/cm2, but decreased significantly to 2,254 +/- 353/cm2 at the 1-cm segment. In the lower esophageal sphincter, the neuronal count increased again to 8,530 +/- 1,606/cm2. Flash-frozen cryosections, which produced neuronal morphology similar to the in vivo condition, showed that there was no difference in neuronal size between esophageal body and sphincter. These studies show that atypical myenteric plexus localization causes spuriously low neuronal counts reported in the lower esophageal sphincter and that reported neuronal size differences are technique-dependent.
Article
To determine the effect of contraction of the diaphragm on the lower esophageal sphincter (LES) pressure, we studied eight healthy volunteers during spontaneous breathing, maximal inspiration, and graded inspiratory efforts against a closed airway (Muller's maneuver). Electrical activity of the crural diaphragm (DEMG) was recorded from bipolar esophageal electrodes, transdiaphragmatic pressure (Pdi) was calculated as the difference between gastric and esophageal pressures, and LES pressure was recorded using a sleeve device. During spontaneous breathing, phasic inspiratory DEMG was accompanied by phasic increases in Pdi and LES pressure. With maximal inspiration, DEMG increased 15-20-fold compared with spontaneous inspiration, and LES pressure rose from an end-expiratory pressure of 21 to 90 mmHg. Similar values were obtained during maximal Muller's maneuvers. LES pressure fell promptly when the diaphragm relaxed. Graded Muller's maneuver resulted in proportional increases in the Pdi, LES pressure, and DEMG. The LES pressure was always greater than Pdi and correlated with it in a linear fashion (P less than 0.001). We conclude that the contraction of the diaphragm exerts a sphincteric action at the LES, and that this effect is an important component of the antireflux barrier.
Article
The responses of the lower esophageal sphincter (LES), stomach, and diaphragm and their contribution to changes in the high-pressure zone (HPZ) at the gastroesophageal junction were determined during extrinsic abdominal compression or intragastric balloon distension in anesthetized cats. Abdominal compression consistently induced an increase in intraluminal end-expiratory LES and gastric pressure (P less than 0.01). Changes in LES pressure significantly exceeded the changes in gastric pressure (P less than 0.01). In contrast, the LES response during gastric distension was variable in the group of animals despite a consistent volume-dependent increase in gastric pressure. Mean LES pressure for the group was unchanged, although 33% of individual animals exhibited a decrease in LES pressure during gastric distension. Both abdominal stimuli induced sustained inhibition of crural (P less than 0.01), but not costal, diaphragmatic electromyographic activity. Vagotomy affected the LES but not the gastric or diaphragmatic responses to both stimuli. In the group of animals, the combined effect of the changes in the three measured variables on the HPZ resulted in maintenance of the antireflux barrier during abdominal compression but a significant decrease in the barrier during gastric distension.
Article
Changes in length of costal and crural segments of the canine diaphragm were measured by sonomicrometry within the first 100-300 ms of inspiration during CO2 rebreathing in anesthetized animals. Both segments showed small but significant decreases in end-expiratory length during progressive hypercapnia. Although both costal and crural segments showed electromyographic activity within the first 100 ms of inspiration, in early inspiration crural shortening predominated with minimal costal shortening. Neither segment contracted isometrically early in inspiration in the presence of airway occlusion. The amount of crural shortening during airway occlusion exceeded costal shortening; both segments showed increased shortening with prolonged occlusion and increasing CO2. Costal and crural shortening at 100 ms was not different for unoccluded and occluded states. These observations suggest that neural control patterns evoke discrete and unequal contributions from the diaphragmatic segments at the beginning of an inspiration; the crural segment may be predominately recruited in early inspiration. Despite traditional assumptions about occlusion pressure measurement (P0.1), diaphragm segments do not contract isometrically during early inspiratory effort against an occluded airway.
Article
The opossum has served as a useful animal model for in vivo studies of lower esophageal sphincter (LES) function. Previous investigations, however, have been confined to studies on anesthetized animals. In 10 opossums we investigated LES pressure during fasting cycles of the gastrointestinal migrating myoelectric complex (MMC) and examined the influences of anesthesia and feeding on LES pressure. Intraluminal pressure from the esophageal body, LES, and gastric antrum was recorded by a manometric assembly that incorporated a sleeve device. Myoelectric activity was recorded from the gastric antrum and duodenum via implanted electrodes. MMCs were readily recorded from all animals. MMC cycle length was 86 +/- 2.9 (SE) min. The LES exhibited cyclic changes in intraluminal pressure that occurred in synchrony with the gastric MMC cycle. During phase I of the gastric MMC cycle, LES pressure was essentially stable, although intermittent spontaneous oscillations at 3-4/min were sometimes noted. Forceful phasic LES contraction started during phase II of the gastric MMC, became maximal during phase III, and disappeared during phase I. The MMC-related phasic LES contraction occurred at a maximal rate of 1.4 +/- 0.05/min with amplitudes of 60-150 mmHg and were temporally associated with spike bursts and contractions in the gastric antrum. Pentobarbital sodium-induced anesthesia abolished MMC-related phasic LES activity and caused a transient rise in basal sphincter pressure. Phasic LES activity was also inhibited by atropine and feeding.(ABSTRACT TRUNCATED AT 250 WORDS)
Article
In order to determine the effect of esophageal movement on tracings of intraluminal pressure, the esophageal body, lower esophageal sphincter, and diaphragmatic hiatus were labeled with metal markers in cats. Metal markers also identified the location of manometric tube recording orifices. Cineroentgenograms and intraluminal esophageal pressure tracings were obtained simultaneously during respiration, peristalsis, and abdominal compression. During each of these conditions, the esophagus, particularly the lower esophageal sphincter, was shown to move significantly in relation to the relatively fixed position of manometric recording sites. This relative movement influences the intraluminal pressure tracing and should be considered when designing methods for recording and scoring esophageal pressure.
Article
. 1. The continuous withdrawal method which has been used successfully in animal experiments for recording pressure profiles in the lower oesophageal sphincter, LES, was applied for the first time in human studies. A catheter with 4 side holes which served as a pressure transmitter, was continuously withdrawn from the stomach at a constant speed (6 mm/sec.) while constantly perfused (5 ml/min.). This procedure shows numerous advantages, particularly for quantitative analysis, when compared to both the stepwise pull-through method and an open-side catheter lying stationary in the sphincter. Thus the profiles obtained using the continuous withdrawal method are remarkable for their definition. Displacements, which can occur with a stationary catheter, are eliminated, and the pressure maximum can be definitely determined even if there is a shift in the area of maximum pressure. – 2. Pressure profiles of the LES taken with the withdrawal method in 20 conscious subjects usually showed a gradual, and then more rapid increase from aboral to oral, which after reaching a maximum value decreased steeply and changed into sub-zero pressures. The maximum pressure taken from the pressure profiles of 20 subjects, being the mean value of all experiments, was 19 ± 7.3 mm Hg with a mean sphincter length of 3.4 ±0.6 cm (x̄±SD). The pressure profiles could be recorded at short intervals (0.5-2 min.) without appreciable irritation of the sphincter. – 3. The continuous withdrawal method proved especially efficient, even after an increase of the sphincter tone induced by Pentagastrin (0.6 μg/kg I. V.). The mean results of the experiments in 6 test subjects showed that the maximum pressure in the LES increased from 13 ± 6.3 mm Hg to 44.2 ± 11 mm Hg 1 min. after the injection and the mean sphincter length increased from 3.9 ±1.2 cm to 5.3±1.4cm. These effects had subsided after 7–10 min. Pressure profiles obtained in this way, as well as supplementary measurements, indicated that Pentagastrin can cause a shift of the maximum pressure area in the oral direction.
Article
Resting pressures recorded from the anal sphincter by the open-tip method seem to reflect the last pressure to which the catheter tip was exposed before it entered the sphincter, presumable because sphincter tissues "seal" the recording orifice and thereby "trap" pressure within the recording system. By injecting or infusing small increments of fluid into the system, one can measure a physiologically meaningful pressure--the pressure required to break the "seal." For the resting sphincter, this pressure has been termed the resting yield pressure; for the maximally tightened sphincter, the augmented yield pressure. By determining yield pressures before and during active contraction of the sphincter the involuntary and voluntary components of sphincter function can be separately assessed. Measurement of yield pressures can separate sphincters judged competent or incompetent on clinical grounds. Injection of microliter quantities of fluid into the recording catheter whose tip is in the sphincter causes a marked rise in pressure. Although "bleeders" or constant slow infusions of fluid do not affect pressures recorded from within a cavity, they do significantly alter pressures recorded from a sphincter zone.
Article
To measure the effect of a sliding (concentric) hiatus hernia on gastroesophageal sphincter competence, 75 patients were studied: 25 patients without esophageal symptoms and without hiatus hernia (Group A); 25 patients without esophageal symptoms but with hiatus hernia (Group B); and 25 patients with symptoms of severe gastroesophageal reflux, with or without a hiatus hernia (Group C). In Group C, 12 patients had a hiatus hernia, and 13 did not. Symptomatic patients were readily separated from asymptomatic ones both by a weaker base-line sphincter strength and by decreased sphincteric response to the stimulus of an increase in intraabdominal pressure. However, in neither the asymptomatic nor the symptomatic groups of patients could any effect of hiatus hernia be found. A hiatus hernia apparently has no effect on gastroesophageal sphincter competence. The rationale for surgical repair of hiatus hernia in patients with gastroesophageal reflux must therefore be questioned.
Article
Measurement of sphincter force of closure has been achieved by utilizing intraluminal infusion of microliter quantities of fluid. This infusion causes an elevation in recorded pressure (yield pressure) when the catheter tip is within a sphincter. The yield pressure agrees exactly with force of closure in a model sphincter and predicts model sphincter strength more exactly than do other methods currently employed for sphincter measurement. The infusion system described has been used to study 40 subjects whose degree of lower esophageal sphincter competence has been defined on either clinical grounds (symptom of heartburn) or by objective measurement (Tuttle test). Subjects with competent sphincters had significantly higher yield pressures than did those subjects without competent sphincters. The overlap of yield pressures was least when the presence or absence of competence was defined by the Tuttle test. No significant difference between competent and incompetent sphincters was found when resting lower esophageal sphincter pressures were measured. It is concluded that infusion of microliter quantities of fluid into the lumen of a closed sphincter allows more accurate prediction of sphincter force of closure than does static measurement of intrasphincteric pressure.
Article
In recent years, considerable new information has become available on the pathogenesis, diagnosis and therapy of gastroesophageal reflux. Gastric contents, mucosal resistance, esophageal acid clearance, and gastric emptying are now recognized, along with incompetency of the lower esophageal sphincter, as contributing factors to gastroesophageal reflux disease. The potential tests for reflux are reviewed and the diagnostic accuracy of each is evaluated. A diagnostic approach to the patient with reflux symptoms is outlined that considers the sensitivity and specificity of these various tests as well as their availability to the generalist and gastrointestinal specialist. Finally, an overview of the current therapy for reflux disease summarizes the controlled studies in the medical literature.
Article
The change in pressure of competent and incompetent lower esophageal sphincter (LES) due to abdominal compression is still a controversial subject. Therefore, we studied the effect of sustained (SAC) and intermittent (IAC) abdominal compression on lower esophageal sphincter pressure (LESP) in normals (N), patients with hiatus hernia (HH), and patients with scleroderma (S). When resting lower esophageal sphincter pressure exceeded 15 mm Hg, response to SAC and IAC was similar in patients with HH and in normals. On the other hand when basal LESP was below 15 mm Hg, stimulated sphincter pressure during IAC was significantly lower than during SAC. Values recorded during SAC were also falsely high in patients with scleroderma. Values obtained during either SAC or IAC did not depend on presence or absence of reflux symptoms in any group. LES stimulation with IAC gives valid results which correlate closely with LESP. Stress tests with IAC therefore seem to be a useful stimulation test for the analysis of LES function.
Article
The in vivo lower esophageal sphincter was identified in cats, using a pressure measuring probe with a perfused side opening adjacent to a metal plug obstructing the distal tip. A suture was placed, under fluoroscopy, at the point of highest pressure. The esophagus and stomach were removed and mounted on a wax block. Consecutive rings were cut from the lower esophageal sphincter region, with blades in a block 1.75 mm apart, and mounted in a muscle bath. Force-length curves were obtained in standard Tyrode solution, in Tyrode with high KCl, and in calcium-free Tyrode with ethylenediaminetetraacetic acid disodium salt to determine basal, total, and passive forces respectively. Active force was obtained as the difference between total and passive force. The ring identified by the suture is located immediately above the squamocolumnar junction. It exhibits the steepest basal force-length curve. The ring also exhibits the highest active and total force under maximal KCl stimulation. The passive force of this ring is the same as for esophageal rings. It is concluded that the highest pressure point in the in vivo lower esophageal sphincter occurs where circular muscle is capable of generating the highest basal, active, and total force. The higher active forces observed at the in vivo high pressure point, however, are due to a thickening of the circular muscles, while the higher basal forces are partly due to increased ability to generate stress (force per unit area of muscle) in the basal state.
Article
The results of this study show that lower esophageal sphincter contractions occur during phases 2 and 3 of the gastric interdigestive migratory motor complex in humans. In one series of studies, esophageal, gastric, and duodenal pressures were monitored overnight for 12 h in 7 healthy, fasting subjects. A second group of 10 volunteers was studied for 12 h on two consecutive nights. Periods of gastric contraction that reached a maximum frequency of about 3/min were shown to be part of the migratory motor complex cycle because they occurred immediately before phase 3 migratory motor complex activity in the duodenum. In all subjects, gastric interdigestive contractions were accompanied by lower esophageal sphincter contractions that maintained a pressure barrier between the stomach and esophageal body. During late phase 2 and phase 3 gastric migratory motor complex activity, the lower esophageal sphincter contractions were especially vigorous. Mean basal lower esophageal sphincter pressure varied significantly during the interdigestive cycle. Lower esophageal sphincter pressure values were maximal during phase 3 of gastric migratory motor complex activity and minimal values occurred during phase 1. No episodes of gastroesophageal reflux occurred as a result of increase of intragastric pressure caused by interdigestive gastric contractions.
Article
During the past decade, considerable new information has accrued about reflux esphagitis and the physiology of esophageal motor function. Although numerous reports review the clinical, diagnostic, and therapeutic aspects of reflux esophagitis, few reports focus primarily on the pathophysiology of esophagitis production. Our purpose here is to review critically recent findings relevant to the pathophysiology of reflux esophagitis, analyze factors that may contribute to the production of reflux esophagitis, and identify appropriate questions that merit further investigation. Throughout the report we will endeavor to alert the reader when the manuscript reflects our own opinion, speculation, or scientific bias as opposed to established observations. For this report the term reflux esophagitis is defined as esophageal inflammation caused by refluxed material. On endoscopy reflux esophagitis may cause visible discoloration, friability, ulceration, exudate, or luminal narrowing. In active reflux esophagitis, histologic sections demonstrate an acute polymorphonuclear or a mixed polymorphonuclear and round cell infiltrate, generally accompanied by epithelial erosion or ulceration. These gross or histologic findings are necessary for a specific diagnosis of reflux esophagitis. In some patients with clinical complaints suggesting GE reflux, the esophagus appears normal at endoscopy and no evidence of inflammation is present on biopsy. Biopsies in such patients, however, often show hyperplastic epithelial changes believed to be stimulated by GE reflux. The term GE reflux changes refers to patients who have hyperplastic changes of the esophageal epithelium unaccompanied by inflammatory esophagitis. The designation GE reflux disease may be used to include patients with either reflux esophagitis or reflux changes. Because some ambiguity exists about the meaning of reflux changes, the focus of this report is on reflux esophagitis.
Article
We studied the action of the costal and crural (vertebral) parts of the diaphragm on the lower rib cage in normal supine dogs. The two parts of the diaphragm were separately stimulated by electrodes directly implanted in the muscle or via the different phrenic nerve roots in the neck. The results of the experiments indicate the following. 1) The costal and crural parts of the diaphragm have a different segmental innervation and a different mechanical action on the rib cage. 2) The costal diaphragm expands the lower rib cage when it contracts. This rib-cage expansion is due mostly to the fulcrum of the abdominal contents and partly to the rise in abdominal pressure that takes place during diaphragmatic contraction. The pericardial attachments play no role in this action of the diaphragm. 3) The action of the crural diaphragm on the lower rib cage depends only on the balance between the inspiratory force exerted by the rise in abdominal pressure and the expiratory force exerted by the fall in pleural pressure. In the intact animal at functional residual capacity, these two opposite effects cancel each other. 4) The inflationary action of both parts on the rib cage decreases progressively as lung volume increases. The findings also suggest that the rise in abdominal pressure which occurs when the diaphragm contracts expands the lower rib cage by acting through the area of apposition of the diaphragm to the rib cage. These findings also strengthen the idea that the diaphragm actually consists of two muscles.
Article
The location and perimeter of the true muscular gastroesophageal junction or cardia were determined during operation in 6 patients with achalasia, in 20 control subjects, and in 40 patients with reflux esophagitis. These two latter groups were submitted to highly selective vagotomy, owing to duodenal ulcer in the control subjects and as part of the surgical technique in reflux esophagitis patients. The careful dissection and isolation of the distal 5-6 cm of the esophagus and esophagogastric junction permitted us to measure the location and perimeter very precisely. There was a very close correlation between the distance incisors-beginning of gastroesophageal sphincter measured preoperatively and the distance incisors-cardia measured during surgery. The cardia could be clearly identified by external inspection corresponding to the limit between the longitudinal muscle layer of the esophagus and the serosal surface of the stomach. The perimeter of the cardia in the patients with reflux esophagitis was significantly larger than the perimeter of the control subjects (p less than 0.001). Intraoperative manometry demonstrated that the external limit of the cardia corresponded to the beginning of the gastroesophageal sphincter. Patients with achalasia had significantly smaller perimeter than controls or reflux esophagitis patients (p less than 0.001).
Article
This study investigates whether asymptomatic lower esophageal mucosal rings are associated with a hiatus hernia or whether they represent an upward migration of columnar epithelium into the esophagus. Simultaneous manometric and potential difference measurements were performed in 12 patients with radiologically documented lower esophageal rings and in 15 control subjects. Suction biopsies from the lower esophagus confirmed that the potential difference transitional zone identified the mucosal gastroesophageal junction. In both patients and controls the esophagogastric mucosal junction was identified within or below the lower esophageal sphincter. It is concluded that the lower esophageal mucosal ring marks the lower end of the esophagus and does not represent a dislocation of the esophagogastric mucosal junction away from the lower esophageal sphincter.
Article
Intraluminal pressures recorded from the stomach and esophagus of 3 asymptomatic normal subjects demonstrated that in 2 subjects only the intraabdominal segment of the inferior esophageal sphincter maintained the sphincteric barrier against reflux when intragastric pressure was elevated by the application of extrinsic pressure to the abdominal wall.
Vasoactive intestinal peptide as a possible neurotransmitter of noncholinergic, nonadrenergic neurons
  • Goyal
Disassociation of costal and crural contractile effects on the gastroesophageal high pressure zone (abstract)
  • Altschuler
Characteristics of sphincteric action of crural diaphragm and lower esophageal sphincter (abstract)
  • Mittal