Radial asymmetry of the upper oesophageal sphincter pressure profile: fact or artefact.

Radial asymmetry of the upper oesophageal sphincter high-pressure zone (UESHPZ) is an accepted notion based on manometric studies. Our aim was to evaluate the effect of the catheter diameter and configuration on the resting pressure profile of the UES. We studied 14 young (30 +/- 2 years) and 14 healthy elderly volunteers (77 +/- 2 years) using the station pull-through technique. We used a specially designed water perfused manometric assembly that incorporated a proximal round cross-section (4.8 mm) and a distal flat cross-section (4.8 x 1.2 mm). Anterior and posterior manometric sites on the round catheter measured significantly higher pressure values than did the sites oriented laterally at the same level (P < 0.001) in both young and elderly. In contrast, the flat-shaped catheter measured statistically indistinguishable pressures from all four orientations in both age groups. In both young and elderly the anterio-posterior, but not lateral pressures by the round catheter were significantly higher (P < 0.001) than those of the flat catheter. An exaggerated anteriorly and posteriorly oriented pressure may be recorded compared with lateral pressures depending on the diameter and non-conforming shape of the recording catheter with respect to the UES producing the appearance of radial asymmetry in the UESHPZ.

Gender differences in cortical representation of rectal distension in healthy humans.

Cerebral cortical processing of information relayed via visceral afferents is poorly understood. We determined and compared cortical activity caused by various levels of rectal distension in healthy male and female subjects. Twenty-eight healthy, young (20-44 yr) volunteer subjects (13 male, 15 female) were studied with a paradigm-driven functional magnetic resonance imaging (fMRI) technique during barostat-controlled rectal distension at perception threshold and 10 mmHg below and above perception threshold. Male subjects showed localized clusters of fMRI activity primarily in the sensory and parietooccipital regions, whereas female subjects also showed activity in the anterior cingulate and insular regions. A progressive increase in maximum percent fMRI signal change and total volume of cortical activity was associated with the intensity of rectal distension pressure in both genders. Regions of cortical activity for below-threshold stimuli showed less substantial signal intensity and volume than responses for threshold and above-threshold stimuli. Volume of cortical activity during rectal distension in women was significantly higher than that for men for all distensions. We conclude that 1) there are substantial differences in female cortical activation topography during rectal distension compared with males; 2) intensity and volume of registered cortical activity due to rectal stimulation are directly related to stimulus strength; and 3) rectal stimulation below perception level is registered in the cerebral cortex.

Cerebral cortical representation of reflexive and volitional swallowing in humans.

The purpose of this study was to compare cerebral cortical representation of experimentally induced reflexive swallow with that of volitional swallow. Eight asymptomatic adults (24-27 yr) were studied by a single-trial functional magnetic resonance imaging technique. Reflexive swallowing showed bilateral activity concentrated to the primary sensory/motor regions. Volitional swallowing was represented bilaterally in the insula, prefrontal, cingulate, and parietooccipital regions in addition to the primary sensory/motor cortex. Intrasubject comparison showed that the total volume of activity during volitional swallowing was significantly larger than that activated during reflexive swallows in either hemisphere (P < 0.001). For volitional swallowing, the primary sensory/motor region contained the largest and the insular region the smallest volumes of activation in both hemispheres, and the total activated volume in the right hemisphere was significantly larger compared with the left (P < 0.05). Intersubject comparison showed significant variability in the volume of activity in each of the four volitional swallowing cortical regions. We conclude that reflexive swallow is represented in the primary sensory/motor cortex and that volitional swallow is represented in multiple regions, including the primary sensory/motor cortex, insular, prefrontal/cingulate gyrus, and cuneus and precuneus region. Non-sensory/motor regions activated during volitional swallow may represent swallow-related intent and planning and possibly urge.

Augmentation of deglutitive upper esophageal sphincter opening in the elderly by exercise.

Earlier studies have shown that the cross-sectional area of the deglutitive upper esophageal sphincter (UES) opening in healthy asymptomatic elderly individuals is reduced compared with healthy young volunteers. The aim of this study was to determine the effect of a head-raising exercise on swallow-induced UES opening and hypopharyngeal intrabolus pressure in the elderly. We studied a total of 31 asymptomatic healthy elderly subjects by videofluoroscopy and manometry before and after real (19 subjects) and sham (12 subjects) exercises. A significant increase was found in the magnitude of the anterior excursion of the larynx, the maximum anteroposterior diameter, and the cross-sectional area of the UES opening after the real exercise (P < 0.05). These changes were associated with a significant decrease in the hypopharyngeal intrabolus pressure studied in 12 (real-exercise) and 6 (sham-exercise) subjects (P < 0.05). A similar effect was not found in the sham-exercise group. In normal elderly subjects, deglutitive UES opening is amenable to augmentation by exercise aimed at strengthening the UES opening muscles. This augmentation is accompanied by a significant decrease in hypopharyngeal intrabolus pressure, indicating a decrease in pharyngeal outflow resistance. This approach may be helpful in some patients with dysphagia due to disorders of deglutitive UES opening.

Kinematic and dynamic characteristics of solid pellet movement during the pharyngeal phase of swallowing.

Information on solid particle movement through the pharynx, in addition to its physiologic importance, has relevance to the swallowing of medications in pill form. The purpose of this study was to determine the kinematics of a solid particle during the oral-pharyngeal phase of swallowing. We used a concurrent manometric-videofluoroscopic technique and identified two distinct zones of increasing bolus velocity, one at the tongue base and the other at the pharyngo-upper esophageal sphincter (UES) region. Velocity decreased significantly (p < .05), to 9.0 +/- 1.0 cm/s, while the bolus traversed the area located between the tip of the horizontal epiglottis and the pharyngeal wall. The velocity of the liquid barium bolus head was similar to that of the solid barium pellet. The average bolus tail velocity was relatively constant. The acceleration of the barium pellet was temporally associated with development of an incrementally decreasing pressure distal to the location of the pellet in the hypopharynx and across the UES. In conclusion, the kinematics of a solid particle are similar to those of the head of a liquid bolus, but both are different from bolus tail kinematics. During the pharyngeal phase of swallowing, the area located ahead of the bolus exhibits an incrementally decreasing pressure, caudally. This may facilitate bolus transport and contribute to airway protection.

Determinants of lower esophageal sphincter relaxation induced by esophageal balloon distension in humans.

The determinants of the lower esophageal sphincter relaxation response to esophageal distension have not previously been systematically examined in humans. In this study, 14 healthy subjects were tested using a manometry catheter with a sleeve device and three balloons spaced 5 cm apart. Subjects had up to five distensions with each balloon at four different diameters and two different durations of inflation. The results indicated that 1,170 separate distensions were available for analysis. Sphincter relaxation occurred more frequently (P < 0.005) with larger balloon diameters, yet occurred in only 84% of inflations at the largest diameter. Sphincter relaxation was more often observed with the proximal balloon (P < 0.005) during longer distensions (P < 0.05) and when esophageal contractions occurred above the balloon (P < 0.005). Once sphincter relaxation occurred, its magnitude was essentially independent of balloon site and diameter, distension duration, and the presence of proximal contractions. In conclusion, even large balloon distensions do not uniformly produce or maintain lower esophageal sphincter relaxation. Sphincter relaxation is more likely with proximal esophageal distension. The association of sphincter relaxation with vagally mediated proximal contractions suggests vagal modulation of this response.

Determinants of intrabolus pressure during esophageal peristaltic bolus transport.

Previous manometric studies of esophageal fluid bolus transport in humans have generally ignored the hydrodynamic distinction between intrabolus pressure and pressure within the lumen-occluded, contracting esophageal segment. In this study we obtained concurrent esophageal videofluoroscopic and intraluminal manometric recordings in supine normal volunteers using different bolus volumes and viscosities and abdominal compression. Intrabolus pressure increased with bolus volume, viscosity, and abdominal compression. Esophageal diameter increased with larger bolus volumes, and this increase was correlated with increases in intrabolus pressure. Intrabolus pressure was highest in the bolus tail. Peak intraluminal pressures > 20 mmHg above basal intrabolus pressure almost invariably were associated with effective peristalsis, whereas values of this pressure differential < 20 mmHg frequently were associated with ineffective peristalsis and retrograde bolus escape. Intrabolus pressure can serve as an important indicator of the forces resisting peristaltic transport and the occurrence of ineffective bolus transport.

Manometric characteristics of cervical dysphagia in a patient with the Kearns-Sayre syndrome.

The manometric findings of deglutitive pharyngoesophageal function in a patient with the Kearns-Sayre syndrome and cervical dysphagia are described. These findings indicate that striated muscles of the pharynx, upper esophageal sphincter (UES), and proximal esophagus are involved. Near absence of pharyngeal peristalsis, abnormally low UES resting pressure, and absence of proximal esophageal peristalsis characterize the manometric findings in this patient. It is conceivable that in mild cases, a combination of various degrees of severity of the above findings may exist.

Esophagoglottal closure reflex: a mechanism of airway protection.

Abrupt esophageal distention occurs commonly during gastroesophageal reflux, thereby generating a circumstance favorable to esophagopharyngeal regurgitation and laryngeal aspiration of gastric refluxate. The aims of the present study were to examine the glottal response to esophageal distention by air and regional esophageal distention by a balloon. Fifteen healthy volunteers (age, 25 +/- 5 years) were studied while they were in an upright position. Using concurrent videoendoscopy and manometry, glottal and upper esophageal sphincter (UES) responses to abrupt esophageal distention by air injection (10-60 mL) and balloon distention (1.5, 2.0, and 2.5 cm) were recorded simultaneously. In addition, 6 subjects were studied with concurrent synchronized videofluoroscopy. Results showed that esophageal distention by air at a threshold volume of 10-60 mL caused vocal cord closure. The UES response to this threshold volume was variable. Volumes larger than the threshold value caused complete UES relaxation and belching. In addition to vocal cord closure, belching was accompanied by anterior movement of the glottis. On videofluoroscopy, the hyoid bone moved anteriorly in association with belching, but not with vocal cord closure without belching. Proximal esophageal distention by the balloon also provoked vocal cord closure. This response was less consistent for balloon distention in the middle and distal esophagus. It is concluded that (a) esophageal distention by either air or a balloon evokes a glottal closure mechanism, thereby suggesting the existence of an esophagoglottal reflex; (b) this reflex is elicited most easily by distention of the proximal esophagus; (c) glottal and UES responses to esophageal distention are independent from each other; and (d) the esophagoglottal closure reflex may play an important role in preventing laryngeal aspiration of acid due to gastroesophageal reflux accompanied by acid regurgitation into the pharynx.

Gastrointestinal motor effects of erythromycin in humans.

The effects of an antibacterially effective IV dose of erythromycin on gastrointestinal motor activity were investigated in eight normal healthy human volunteers in the fasted state and the fed state. Motor activity was recorded by a multilumen manometric tube. Data were analyzed visually and by a computer method. Blood samples were obtained for erythromycin and motilin assays. In the gastric antrum, erythromycin significantly increased the total duration, amplitude, and area under contractions from 0 to 60 minutes and frequency of contractions from 0 to 30 minutes from the start of its infusion in the fasted state. A similar response in the fed state occurred mostly from 0 to 30 minutes after the start of erythromycin infusion. By contrast, erythromycin inhibited the frequency and decreased the duration of small intestinal contractions in the fed state but had no effect in the fasted state. The gastric motor response was related to the plasma concentration of erythromycin, but not to plasma motilin. Erythromycin significantly shortened the duration of migrating motor complex disruption by a meal. Erythromycin also induced symptoms of upper abdominal pain, bloating, and nausea. Abdominal pain was related to strong antral contractions in both fasted and fed states; bloating occurred only in the fed state. Nausea occurred in both fasted and fed states, but it was not related to any specific pattern of motor activity. It is concluded that the strong antral contractions induced by erythromycin may accelerate the rate of gastric emptying, but they may also be responsible for causing the sensations of upper abdominal pain and bloating. The motor response to erythromycin is less during the fed than during the fasted state. The strong antral contractions induced by erythromycin are not mediated by the release of motilin.

Myogenic oscillatory mechanism for opossum esophageal smooth muscle contractions.

We evaluated the control of phasic contractions in opossum esophageal circular smooth muscle by determining the contractile response in vitro to agents that cause membrane depolarization and excitation by different mechanisms. Transverse muscle strips taken from different sites along the length of the smooth muscle esophagus were exposed to progressively increasing concentrations of tetraethylammonium (1-30 mM), K+ (4.6-30 mM), or bethanechol (10(-6) to 10(-2) M). In normally inactive esophageal circular smooth muscle, tetraethylammonium and high K+ concentration elicited phasic contractions that were not blocked by atropine and tetrodotoxin. Bethanechol, an M2 muscarinic receptor agonist that acts selectively on smooth muscle, elicited phasic contractions that were not blocked by tetrodotoxin. We conclude that a latent myogenic oscillatory mechanism for control of phasic contractions exists in esophageal circular smooth muscle and that it may be activated by nonspecific excitation of the smooth muscle membrane. We suggest that this myogenic oscillatory mechanism is likely excited and modulated by nerves.

Coordination of deglutitive glottic closure with oropharyngeal swallowing.

The goals of this study were to quantify the temporal relationship between swallow-induced glottic closure and (a) signals of swallow initiation, such as hyoid bone movement, tongue base movement, and mylohyoid electrical activity; (b) pharyngeal peristalsis; (c) laryngeal elevation; (d) vestibular closure; and (e) oropharyngeal barium bolus transit. Eight normal subjects (age 20-30 yr) were studied by concurrent transnasal video laryngoscopy, pharyngeal intraluminal manometry, and submental surface electromyography. The manometric, electromyographic, and both video recordings were synchronized with one another using a specially designed event marker. Dry, 5-ml water, and 5-ml barium swallows were recorded. Frame-by-frame analysis of the video endoscopic recordings showed that deglutitive laryngeal kinetics consisted of vocal cord adduction associated with transverse approximation of the arytenoids followed by vertical approximation of arytenoids to the base of the epiglottis followed by laryngeal ascent and epiglottic descent. Onset of swallow-induced vocal cord adduction preceded the onset of hyoid bone movement, base of the tongue movement, and submental surface myoelectric activity by 0.33 +/- 0.04 (SE) s, 0.31 +/- 0.04 s, and 0.38 +/- 0.04 s, respectively. Onset of vocal cord adduction also preceded the initiation of peristalsis in the nasopharynx and its propagation to oropharynx and upper esophageal sphincter by 0.64 +/- 0.05 s, 0.82 +/- 0.05 s, and 1.08 +/- 0.04 s, respectively. The time between the onset of vocal cord adduction and their return to full opening was 2.2 +/- 0.09 s. It was concluded that (a) among events evaluated, vocal cord adduction is the initial event during the swallowing sequence; (b) laryngeal kinetics during deglutition have distinctive features, and their close coordination with other swallowing events suggests that they are an essential feature of the swallowing program; and (c) abnormal laryngeal kinetics or lack of coordination between the glottic closure mechanism and oropharyngeal bolus transport may have an important role in swallow-induced aspiration.

Oesophageal acidification does not increase lower oesophageal sphincter pressure.

We studied the effect of distal oesophageal acidification on lower oesophageal sphincter (LOS) pressure in normal human volunteers and in cats. The distal oesophagus was acidified by intraluminal injection of 0.1N HCl (pH 1.2). The LOS pressure was recorded by a sleeve device while pharyngeal and oesophageal pressures were monitored by nonperfused, water filled catheters. In normal human subjects, distal oesophageal acidification did not elicit a change in LOS pressure. In anaesthetised cats, injection of acid into the distal oesophagus elicited immediate LOS relaxation followed by a secondary peristaltic sequence. With propagation of the peristaltic sequence into the LOS, the LOS pressure abruptly increased 20-100 mmHg and gradually returned to the preinjection value over 15-180 s. In the one instance in which we were able to acidify the distal oesophagus without evoking secondary peristalsis, the LOS pressure did not change. Injection of saline into the distal oesophagus evoked a response in the LOS and oesophageal body that was indistinguishable from that seen with acid. We conclude that contrary to common belief, distal oesophageal acidification itself does not affect LOS pressure in man or the cat.

Spatial and temporal patterns of human jejunal contractions.

We recorded human jejunal motor activity by a 12-lumen manometric tube with recording sites 2 cm apart. The contractile activity in the fasted and the fed state was analyzed by computer to define the spatial and temporal patterns of contractions. Mean duration and area of single contractions during phase III activity were not different from those during phase II activity. By contrast, the frequency and amplitude of contractions, their propagation distance, and the percentage of contractions that propagated for greater than or equal to 2 cm were significantly greater during phase III than during phase II activity. The mean frequency and percentage of propagated contractions in the fed state were intermediate between those during phase II and phase III activity. Mean propagation distance of postprandial contractions was not different from that of phase II contractions. Most contractions in the fed state were uncoordinated at adjacent recording sites. Occasionally, large-amplitude and long-duration contractions, called individual migrating contractions, propagated over long distances and frequently over the entire 22-cm study segment. We conclude that there are some significant differences between the spatial and temporal patterns of contractions between the fed state and phase II and phase III activity. The largely disorganized phasic contractions in the fed state may cause mostly mixing of the ingested meal and its slow distal propagation, whereas the infrequent individual migrating contractions may rapidly propel intestinal contents over longer distances.

Effects of morphine on the human sphincter of Oddi.

The effects of morphine on intraluminal pressures recorded from the sphincter of Oddi (SO) at endoscopic retrograde cholangiopancreatography in 19 patients who were without evidence of biliary or pancreatic disease were studied. Morphine was given in four successive doses of 2.5, 2.5, 5, and 10 micrograms/kg iv at five minute intervals. Morphine in subanalgesic doses increased the frequency of SO phasic pressure waves to a maximum of 10-12/min, caused the phasic waves to occur simultaneously along the sphincter segment, increased phasic wave amplitude from 72 (26) (SE) to 136 (31) mmHg, and increased SO basal pressure from 10 (1) to 29 (9) mmHg (p less than 0.05). The effects of morphine on the SO are mediated by more than one opioid receptor type, as naloxone competitively antagonised the increase in phasic wave frequency induced by morphine, but did not affect the increase in SO basal pressure elicited by morphine. When given after naloxone, morphine decreased phasic wave amplitude, an inhibitory effect that is normally masked by morphine's dominant naloxone sensitive excitatory effect. Mu receptors do not appear to be involved in control of spontaneous SO motor function, as naloxone alone did not affect SO motor activity. The excitatory effects of morphine on the SO are not mediated by cholinergic nerves, as they were not blocked by atropine. Cholinergic nerves, however, may have a role in regulating spontaneous SO motor function because atropine alone depressed phasic wave activity and basal pressure. Although morphine does cause 'spasm' of the human SO, its effects are more complex than is commonly believed.

A method for continuous monitoring of upper esophageal sphincter pressure.

We tested a manometric assembly employing a sleeve sensor that is able to monitor anterior or posterior pressure in the human upper esophageal sphincter (UES) for prolonged intervals. When compared to rapid pull-through measurement of UES pressure obtained with conventional manometric assemblies, the sleeve sensor measured significantly lower UES pressures with less variability between subjects, thereby suggesting that the rapid pull-through maneuver stimulates the UES to contract. Concurrent recordings of UES pressure with a sleeve sensor and a side-hole sensor during a slow station pull-through yielded almost equal pressure values at the peak of the high-pressure zone (station zero), but the side-hole site recorded significantly lower pressures than the sleeve at stations 0.5 cm or more from the peak of the high-pressure zone. During 10 min of recording at station zero, the sleeve sensor recorded greater pressures than the side-hole sensor. This finding demonstrated the suceptibility of the side-hole sensor to axial movement relative to peak UES pressure. When stationary, both the sleeve sensor and the side-hole sensor recorded significantly lower UES pressure after 1-2 min of recording, again suggesting that movement of the recording assembly stimulates the UES to contract. Sleeve recordings of swallow-induced UES relaxations showed that UES relaxations induced by water swallows were slightly longer than those induced by dry swallows. Augmentations of UES pressure induced by balloon distension of the esophageal body were also recorded. We conclude that the sleeve sensor is a suitable method for investigating the normal physiology and pathophysiology of the UES in human subjects.

Effect of sleep, spontaneous gastroesophageal reflux, and a meal on upper esophageal sphincter pressure in normal human volunteers.

Owing to the inherent difficulties of recording upper esophageal sphincter pressure, little is known about normal upper esophageal sphincter physiology. In this study we used a modified sleeve device to record upper esophageal sphincter pressure continuously in 8 normal volunteers. Intraesophageal pH and electroencephalogram activity were also recorded to document the occurrence of spontaneous gastroesophageal reflux and sleep. After an hour of baseline recording, the subjects ate a meal. Recording was then resumed for an additional 7 h during which period the subjects slept part of the time. The mean upper esophageal sphincter pressure was measured for each 10-min epoch. Electroencephalogram recordings were read blindly for the presence and stage of sleep. Periods of sleep were then correlated with the manometric tracings. Mean upper esophageal sphincter pressure during wakefulness, stage 1 sleep, and deeper sleep was 40 +/- 17 (SD), 20 +/- 17, and 8 +/- 3 mmHg, respectively. A significant change in upper esophageal sphincter pressure did not occur postprandially or during episodes of spontaneous gastroesophageal reflux. Upper esophageal sphincter pressure was observed to increase transiently with each inspiration during periods of restfulness and sleep, a response consistent with the hypothesis that one function of the upper esophageal sphincter is to exclude air from the esophagus during respiration. The demonstration that upper esophageal sphincter pressure falls markedly during sleep may have significance in that this diminishes the barrier to nocturnal regurgitation and potential aspiration.

Chronic recurrent pancreatitis secondary to a submucosal ampullary tumor in a patient with neurofibromatosis.

We report a 45-year-old nonalcoholic patient with Von Recklinghausen's disease and chronic recurrent pancreatitis. On endoscopy, a benign-appearing submucosal tumor surrounded the papilla of Vater. Cannulation of the pancreatic duct showed a dilated ductal system with subsequent delayed drainage. Endoscopic manometry revealed elevated sphincter of Oddi pressures. Endoscopic sphincterotomy resulted in immediate normal drainage of the pancreatic duct and in subsequent clinical improvement.

Esophageal peristaltic dysfunction in peptic esophagitis.

Esophageal exposure to acid is a major determinant in the pathogenesis of reflux esophagitis. In this study, we analyzed the esophageal peristaltic function of 177 patients and asymptomatic volunteers for abnormalities that could lead to prolonged esophageal acid clearance. The subjects were divided into five groups: normal volunteers, patient controls, patients with noninflammatory gastroesophageal reflux disease, patients with mild esophagitis, and ones with severe esophagitis. Manometric data were analyzed for the occurrence of failed primary peristalsis, for the occurrence of feeble peristalsis in the distal esophagus, and for hypotensive lower esophageal sphincter pressure. From an analysis of the data on control patients, peristaltic dysfunction was defined as the occurrence of either failed primary peristalsis or hypotensive peristalsis in the distal esophagus for over half of the test swallows. Peristaltic dysfunction was increasingly prevalent with increasing severity of peptic esophagitis, occurring in 25% of patients with mild esophagitis and 48% of patients with severe esophagitis. A correlation did not exist between the occurrence of peristaltic dysfunction and hypotensive lower esophageal sphincter pressure (less than or equal to 10 mmHg). We conclude that peristaltic dysfunction occurs in a substantial minority of patients with peptic esophagitis and could contribute to increased esophageal exposure to refluxed acid material.

Upper esophageal sphincter function during belching.

We studied the mechanism of belching with specific attention to the upper esophageal sphincter (UES) in 14 normal volunteers. Belching occurred by the following sequence of events: lower esophageal sphincter relaxation; gastroesophageal gas reflux, recorded manometrically as a gastroesophageal common cavity phenomenon; UES relaxation; esophagopharyngeal gas reflux; and restoration of intraesophageal pressure to baseline by a peristaltic contraction. Upper esophageal sphincter relaxations comparable to those associated with belches were induced by abrupt esophageal distention with air boluses. In contrast, fluid boluses injected into the midesophageal body either had no effect on UES pressure or increased UES pressure. Thus, the UES responded to esophageal body distention in two distinct ways: abrupt relaxation in response to air boluses and pressure augmentation in response to fluid boluses. Mucosal anesthesia did not alter the UES response to esophageal boluses of gas or liquid thereby making it unlikely that these substances are differentiated by a mucosal receptor. Rapid distention of the proximal esophagus with a cylindrical balloon (15 cm long) elicited UES relaxation. These findings suggest that the rapidity and spatial pattern of esophageal distention, rather than discrimination of the type of material causing the distention, determines whether or not UES relaxation occurs.