Impaired deglutitive EGJ relaxation in clinical esophageal manometry: a quantitative analysis of 400 patients and 75 controls

Assessing deglutitive esophagogastric junction (EGJ) relaxation is an essential focus of clinical manometry. Our aim was to apply automated algorithmic analyses to high-resolution manometry (HRM) studies to ascertain the optimal method for discriminating normal from abnormal deglutitive EGJ relaxation. All 473 subjects (73 controls) were studied with a 36-channel solid-state HRM assembly during water swallows. Patients were classified as: 1) achalasia, 2) postfundoplication, 3) nonachalasia with normal deglutitive EGJ relaxation, or 4) functional obstruction (preserved peristalsis with incomplete EGJ relaxation). Automated computer programs assessed the adequacy of EGJ relaxation by using progressively complex analysis routines to compensate for esophageal shortening, crural diaphragm contraction, and catheter movement, all potential confounders. The single-sensor method of assessing EGJ relaxation had a sensitivity of only 52% for detecting achalasia. Of the automated HRM analysis paradigms tested, the 4-s integrated relaxation pressure using a cutoff of 15 mmHg performed optimally with 98% sensitivity and 96% specificity in the detection of achalasia. We also identified a heterogeneous group of 26 patients with functional EGJ obstruction attributed to variant achalasia and other diverse pathology. Although further clinical experience will ultimately judge, it is our expectation that applying rigorous methodology such as described herein to the analysis of HRM studies will improve the consistency in the interpretation of clinical manometry and prove useful in guiding clinical management.     

Pressure morphology of the relaxed lower esophageal sphincter: the formation and collapse of the phrenic ampulla

This study aimed to apply novel high-resolution manometry with eight-sector radial pressure resolution (3D-HRM technology) to resolve the deglutitive pressure morphology at the esophagogastric junction (EGJ) before, during, and after bolus transit. A hybrid HRM assembly, including a 9-cm-long 3D-HRM array, was used to record EGJ pressure morphology in 15 normal subjects. Concurrent videofluoroscopy was used to relate bolus movement to pressure morphology and EGJ anatomy, aided by an endoclip marking the squamocolumnar junction (SCJ). The contractile deceleration point (CDP) marked the time at which luminal clearance slowed to 1.1 cm/s and the location (4 cm proximal to the elevated SCJ) at which peristalsis terminated. The phrenic ampulla spanned from the CDP to the SCJ. The subsequent radial and axial collapse of the ampulla coincided with the reconstitution of the effaced and elongated lower esophageal sphincter (LES). Following ampullary emptying, the stretched LES (maximum length 4.0 cm) progressively collapsed to its baseline length of 1.9 cm (P < 0.001). The phrenic ampulla is a transient structure comprised of the stretched, effaced, and axially displaced LES that serves as a "yield zone" to facilitate bolus transfer to the stomach. During ampullary emptying, the LES circular muscle contracts, and longitudinal muscle shortens while that of the adjacent esophagus reelongates. The likely LES elongation with the formation of the ampulla and shortening to its native length after ampullary emptying suggest that reduction in the resting tone of the longitudinal muscle within the LES segment is a previously unrecognized component of LES relaxation.     

Quantifying EGJ morphology and relaxation with high-resolution manometry: a study of 75 asymptomatic volunteers

Our aim was to define normal esophagogastric junction (EGJ) morphology and relaxation characteristics using high-resolution manometry (HRM). To this end, 75 asymptomatic controls underwent HRM with a solid-state manometric assembly incorporating 36 circumferential sensors spaced at 1-cm intervals positioned to record from the hypopharynx to the stomach. Ten 5-ml water swallows were obtained. EGJ relaxation was quantified by 1) nadir pressure, 2) the lowest 3-s mean residual pressure after swallow (E-sleeve), and 3) the transsphincteric gradient 2-6 s after swallowing measured from 2 cm above to 2 cm below the EGJ. A new parameter, integrated relaxation resistance (IRR), was also calculated. The IRR calculation accounted for both the duration of EGJ relaxation and instantaneous E-sleeve-type relaxation pressures during the entire interval of relaxation. The means and ranges (5-95th percentile) for nadir lower esophageal sphincter relaxation pressure (mean: 3.9 mmHg, range: 0-10.1 mmHg) and E-sleeve relaxation pressure (mean: 8.1 mmHg, range: 4.1-15.1 mmHg) were consistent with previously reported values. The mean relaxation interval was 7.95 +/- 0.2 s (mean +/- SE), whereas the median relaxation pressure during that interval was 10.7 +/- 0.5 mmHg (mean +/- SE). Mean IRR was 1.3 mmHg/s (95th percentile: 3.0 mmHg/s). Mean EGJ length was 3.7 cm. In conclusion, HRM provides a seamless dynamic representation of pressure within and across the EGJ. In addition to providing conventional EGJ relaxation parameters, this technology also creates opportunities to quantify more precise measures of EGJ relaxation and morphology.     

Reduced tLESR elicitation in response to gastric distension in fundoplication patients

Transient lower esophageal sphincter relaxations (tLESRs) are vagally mediated in response to gastric cardiac distension. Nine volunteers, eight gastroesophageal reflux disease (GERD) patients, and eight fundoplication patients were studied. Manometry with an assembly that included a barostat bag was done for 1 h with and 1 h without barostat distension to 8 mmHg. Recordings were scored for tLESRs and barostat bag volume. Fundoplication patients had fewer tLESRs (0.4 +/- 0.3/h) than either normal subjects (2.4 +/- 0.5/h) or GERD patients (2.0 +/- 0.3/h). The tLESRs rate increased significantly in normal subjects (5.8 +/- 0.9/h) and GERD patients (5.4 +/- 0.8/h) during distension but not in the fundoplication group. All groups exhibited similar gastric accommodation (change in volume/change in pressure) in response to distension. Fundoplication patients exhibit a lower tLESR rate at rest and a marked attenuation of the response to gastric distension compared with either controls or GERD patients. Gastric accommodation was not impaired with fundoplication. This suggests that the receptive field for triggering tLESRs is contained within a wider field for elicitation of gastric receptive relaxation and that only the first is affected by fundoplication.     

Esophageal tone in patients with total aperistalsis: gastroesophageal reflux disease versus achalasia

We have evaluated esophageal tone in two different conditions that, in some cases, similarly impair phasic esophageal motility. Studies were performed in 14 healthy volunteers, 10 patients with total esophageal aperistalsis secondary to gastroesophageal reflux disease (GERD), and 25 untreated achalasia patients. We quantified esophageal compliance and relaxation induced by a nitric oxide donor using a barostat. Intraesophageal volume at a minimal distending pressure (2 mmHg) was not significantly different among all three groups (4.1 +/- 0.7, 3.8 +/- 0.7, and 4.2 +/- 1.2 ml for healthy, GERD, and achalasia groups, respectively). Esophageal compliance was significantly increased (P < 0.05 vs. healthy group) in the two groups of patients with aperistalsis (1.9 +/- 0.2, 3.0 +/- 0.2, and 3.1 +/- 0.3 ml/mmHg for healthy, GERD, and achalasia groups, respectively). Esophageal relaxation was decreased in GERD patients (Delta diameter: 0.4 +/- 0.1 cm) and increased in achalasia patients (Delta diameter: 1.3 +/- 0.4 cm) relative to healthy subjects (Delta diameter: 0.9 +/- 0.2 cm) (P < 0.05 for GERD vs. achalasia and healthy groups). Our results indicate that diseases that similarly impair phasic esophageal motility may affect esophageal tone differently.     

Utilizing intraluminal pressure differences to predict esophageal bolus flow dynamics

Successful esophageal emptying depends on the generation of a sustained intrabolus pressure (IBP) sufficient to overcome esophagogastric junction (EGJ) obstruction. Our aim was to develop a manometric analysis paradigm that describes the bolus driving pressure difference and the flow permissive time for esophageal bolus transit. Twenty normal subjects were studied with a 36-channel manometry assembly (1-cm spacing) during two 5- and one 10-ml barium swallows and concurrent fluoroscopy. Bolus domain pressure plots were generated by plotting bolus domain pressure (BDP) and EGJ relaxation pressure. BDP was defined as the pressure midway between the peristaltic ramp-up and the proximal margin of the EGJ. The flow permissive time was defined as the period where the BDP was > or = EGJ relaxation pressure. The mean BDP was 11.7 +/- 1.0 mmHg (SE), and the mean flow permissive time was 3.9 +/- 0.4 s for 5-ml swallows in normal controls. The mean BDP difference during flow was 4.0 +/- 1.0 mmHg. There was no significant difference in the fluoroscopic transit time and the flow permissive time calculated from the BDP plots (5 ml: fluoroscopy 3.4 +/- 0.2 s; BDP 3.9 +/- 0.4 s, P > 0.05). BDP plots provide a reliable measurement of IBP and its relationship with EGJ relaxation. The time available for flow can be readily delineated from this analysis, and the driving pressure responsible for flow can be accurately described and quantified. This may help predict abnormal bolus transit and the underlying mechanical properties of the EGJ.     

Complete lower esophageal sphincter relaxation observed in some achalasia patients is functionally inadequate

Generally accepted manometric criteria for the diagnosis of achalasia are absent peristalsis and incomplete lower esophageal sphincter (LES) relaxation. However, in some patients with otherwise typical features of achalasia, esophageal manometry shows complete LES relaxation during swallowing. To establish whether such apparently complete LES relaxations are functionally adequate, we quantified changes in resistance to flow at the esophagogastric junction (EGJ) during wet swallowing. We studied seven achalasia patients with manometrically complete (>80%) LES relaxation, eight achalasia patients with incomplete (<40%) LES relaxation, and eight healthy volunteers. Complete LES relaxation on standard manometry (open-tip catheters) was confirmed in five of the seven achalasia patients by a Dentsleeve. Changes in EGJ resistance to flow were quantified using a pneumatic resistometer. Manometrically, the relaxation time span was significantly longer in patients with complete LES relaxation than in those with incomplete relaxation (7. 3 +/- 0.5 vs. 4.4 +/- 0.7 s; P < 0.05). The fall in EGJ resistance from basal values during swallowing was markedly reduced in both achalasia groups (21 +/- 8% in those with manometrically complete relaxation and 4 +/- 2% in those with incomplete relaxation) by comparison with healthy individuals, in whom resistance fell by 90 +/- 3% (P < 0.05 vs. both achalasia groups). The duration of EGJ resistance drop was also much shorter in achalasia with (0.7 +/- 0.2 s) and without (0.2 +/- 0.1 s) complete LES relaxation compared with healthy control values (6.6 +/- 1.2 s). Our results reveal that the apparently complete LES relaxation observed manometrically in some patients with achalasia is functionally inadequate since it is not associated with the normal profound fall in EGJ resistance to flow.     

Current Advancement on the Dynamic Mechanism of Gastroesophageal Reflux Disease

Gastroesophageal reflux disease (GERD) is a common clinical disease associated with upper gastrointestinal motility disorders. Recently, with improvements in living standards and changes in lifestyle and dietary habits, the incidence of GERD has been increasing yearly. However, the mechanism of GERD has not been fully elucidated due to its complex pathogenesis, and this had led to unsatisfactory therapeutic outcomes. Currently, the occurrence and development of GERD involve multiple factors. Its pathogenesis is mainly thought to be related to factors, such as lower esophageal sphincter pressure, transient lower esophageal sphincter relaxation, crural diaphragmatic dysfunction, hiatus hernia, and impaired esophageal clearance. Therefore, explaining the pathogenesis of GERD more clearly and systematically, exploring potential and effective therapeutic targets, and choosing the best treatment methods have gradually become the focus of scholars'' attention. Herein, we reviewed current advancements in the dynamic mechanism of GERD to better counsel patients on possible treatment options.     

Space-time pressure structure of pharyngo-esophageal segment during swallowing

We applied high-resolution manometry with spatiotemporal data interpolation and simultaneous videofluoroscopy to normal pharyngeal swallows to correlate specific features in the space-time intraluminal pressure structure with physiological events and normal deglutitive transsphincteric bolus flow to define normal biomechanical properties of the pharyngo-esophageal (PE) segment. Pressures were recorded by microperfused catheter, and the two-dimensional space-time data sets were plotted as isocontours. On these were superimposed bolus trajectories, anatomic segment movements, and hyo-laryngeal trajectories from concurrent videofluoroscopy. Correlation of the highly reproducible space-time-pressure structure with radiographic images confirmed that primary deglutitive PE segment functions (pressure profile, laryngeal elevation, axial sphincter motion, timing of relaxation, contraction) are accurately discernible from single isocontour pressure visualization. Pressure during bolus flow was highly dependent on axial location within PE segment and time instant. The intrabolus pressure domain, corresponding to the space-time region between bolus head and tail trajectories, demonstrated significant bolus volume dependence. High-resolution manometry accurately, comprehensively, and highly reproducibly depicts the PE segment space-time-pressure structure and specific physiological events related to upper esophageal sphincter opening and transsphincteric flow during normal swallowing. Intrabolus pressure variations are highly dependent on position within the PE segment and time.     

GERD is associated with shortened telomeres in the squamous epithelium of the distal esophagus

Telomeres are repetitive DNA sequences located at the ends of chromosomes. Telomeres are shortened by repeated cell divisions and by oxidative DNA damage, and cells with critically shortened telomeres cannot divide. We hypothesized that chronic gastroesophageal reflux disease (GERD)-induced injury of the esophageal squamous epithelium results in progressive telomeric shortening that eventually might interfere with mucosal healing. To address our hypothesis, we compared telomere length and telomerase activity in biopsy specimens of esophageal squamous epithelium from GERD patients and control patients. Endoscopic biopsies were taken from the esophageal squamous epithelium of 38 patients with GERD [10 long-segment Barrett's esophagus (LSBE), 15 short-segment (SSBE), 13 GERD without Barrett's esophagus] and 16 control patients without GERD. Telomere length was assessed using the terminal restriction fragment assay, and telomerase activity was studied by the PCR-based telomeric repeat amplification protocol assay. Patients with GERD had significantly shorter telomeres in the distal esophagus than controls [8.3 +/- 0.5 vs. 10.9 +/- 1.5 (SE) Kbp, P = 0.043]. Among the patients with GERD, telomere length in the distal esophagus did not differ significantly in those with and without Barrett's esophagus (LSBE 7.9 +/- 0.8, SSBE 8.6 +/- 0.9, GERD without BE 8.7 +/- 1.0 Kbp). No significant differences in telomerase activity in the distal esophagus were noted between patients with GERD and controls (4.0 +/- 0.39 vs. 5.2 +/- 0.53 RIUs). Telomeres in the squamous epithelium of the distal esophagus of patients who have GERD, with and without Barrett's esophagus, are significantly shorter than those of patients without GERD despite similar levels of telomerase activity.     

Distension during gastroesophageal reflux: effects of acid inhibition and correlation with symptoms

We studied spontaneous gastroesophageal reflux (GER)-induced esophageal distension using ultrasound imaging and its role in the genesis of esophageal symptoms before and during esomeprazole therapy. Ten controls and 10 GER disease (GERD) patients were studied by combined impedance, esophageal pH, manometry, and ultrasonography before and during esomeprazole therapy. Physiological data and symptoms were recorded for 2 h following a standardized meal. From ultrasound images, the esophageal cross-sectional area (CSA) at the peak of GER-induced distension was determined and compared between controls vs. patients, symptomatic vs. asymptomatic GER episodes, and before vs. during esomeprazole in GERD patients. The mean lumen CSA is greater in the patients than controls (271 +/- 71 mm(2) vs. 163 +/- 56 mm(2), P = 0.001) but not different among asymptomatic reflux episodes, and those associated with regurgitation (290 +/- 110 mm(2)) or heartburn (271 +/- 67 mm(2)). Eight chest pain episodes associated with reflux revealed a tendency toward larger mean esophageal distension (459 +/- 40 mm(2)) compared with asymptomatic reflux (268 +/- 70 mm(2), P = 0.058). Following esomeprazole treatment, most GER episodes were nonacidic and asymptomatic except in two patients in whom cyclical reflux was associated with large esophageal distensions. Esomeprazole did not alter the lumen CSA during GER. Esophageal distension is greater in the GERD subjects compared with controls; however, it is unlikely that the GER-induced distension of the esophagus plays a significant role in the genesis of heartburn sensation. Esomeprazole therapy does not alter the GER-induced distension of the esophagus.     

Distension of the esophagogastric junction augments triggering of transient lower esophageal sphincter relaxation

Patients with gastroesophageal reflux disease show an increase in esophagogastric junction (EGJ) distensibility and in frequency of transient lower esophageal sphincter relaxations (TLESR) induced by gastric distension. The objective was to study the effect of localized EGJ distension on triggering of TLESR in healthy volunteers. An esophageal manometric catheter incorporating an 8-cm internal balloon adjacent to a sleeve sensor was developed to enable continuous recording of EGJ pressure during distension of the EGJ. Inflation of the balloon doubled the cross-section of the trans-sphincteric portion of the catheter from 5 mm OD (round) to 5 × 11 mm (oval). Ten healthy subjects were included. After catheter placement and a 30-min adaptation period, the EGJ was randomly distended or not, followed by a 45-min baseline recording. Subjects consumed a refluxogenic meal, and recordings were made for 3 h postprandially. A repeat study was performed on another day with EGJ distension status reversed. Additionally, in one subject MRI was performed to establish the exact position of the balloon in the inflated state. The number of TLESR increased during periods of EGJ distension with the effect being greater after a meal [baseline: 2.0(0.0-4.0) vs. 4.0(1.0-11.0), P=0.04; postprandial: 15.5(10.0-33.0) vs. 22.0(17.0-58.0), P=0.007 for undistended and distended, respectively]. EGJ distension augments meal-induced triggering of TLESR in healthy volunteers. Our data suggest the existence of a population of vagal afferents located at sites in/around the EGJ that may influence triggering of TLESR.     

Adding a radial dimension to the assessment of esophagogastric junction relaxation: validation studies of the 3D-eSleeve

High-resolution manometry (HRM) with esophageal pressure topography (EPT) allowed for the establishment of an objective quantitative measurement of esophagogastric junction (EGJ) relaxation, the integrated relaxation pressure (IRP). This study assessed whether or not a novel 3D-HRM assembly could improve on this measurement. Twenty-five normal subjects were studied with both a standard HRM assembly and a novel hybrid assembly (3D-HRM), including a 9.0 cm 3D-HRM segment composed of 96 radially dispersed independent pressure sensors. The standard IRP was computed using each assembly and compared with a novel paradigm, the 3D-IRP, an analysis premised on finding the axial maximum and radial minimum pressure at each sensor ring along the sleeve segment. Fourteen additional subjects underwent barium swallows with 3D-HRM and concurrent videofluoroscopy to compare the electronic sleeve (eSleeve) paradigm (circumferential average) to the 3D eSleeve paradigm (radial minimum) as a predictor of transphincteric flow. The 3D-IRP was significantly less than all other calculations of IRP with the upper limit of normal being 12 mmHg vs. 17 mmHg for the standard IRP. The sensitivity (0.78) and the specificity (0.88) of the 3D-eSleeve were also better than the standard eSleeve (0.55 and 0.85, respectively) for predicting flow permissive time verified fluoroscopically. The 3D-IRP and 3D-eSleeve calculated using the radial pressure minimum lowered the normative range of EGJ relaxation (upper limit of normal 12 mmHg) and yielded intraluminal pressure gradients that better correlated with bolus flow than did analysis paradigms based on circumferentially averaged pressure.     

The functional lumen imaging probe (FLIP) for evaluation of the esophagogastric junction

There is a need for new methods to study the dynamics of the esophagogastric junction (EGJ). The aims were to verify the efficacy and usefulness of a "functional lumen imaging probe" (FLIP) for the evaluation of the EGJ. Eight healthy volunteers (6 men), median age 26 (21-35) yr, and two achalasia patients underwent the FLIP procedure. The EGJ was located by manometry. The FLIP measured eight cross-sectional areas (CSAs) 4 mm apart together with the pressure inside a saline-filled cylindrical bag. The data showed the geometric profile of the EGJ reconstructed in a video animation of its dynamic activity. A plot of curve-fitted data for the smallest CSA vs. pressure after balloon distension indicated that the pressure increased from 18 cmH2O at a CSA of 38 mm2 to a pressure of 37 cmH2O at a CSA of 230 mm2 for the healthy controls. In one achalasia patient (unsuccessfully treated with dilations), the CSA never rose above the minimal measurable value despite the pressure increasing to 50 cmH2O. In another achalasia patient (successfully treated with dilations), the pressure only reached 15 cmH2O despite opening to a CSA of 250 mm2. In conclusion, FLIP represents the first dynamic technique to profile the function and anatomy of the EGJ. The method can be used practically to evaluate difficult cases of EGJ dysfunction and may provide a role in evaluating patients before and after therapies for diseases affecting the EGJ such as achalasia and gastroesophageal reflux disease.     

Biomechanics of failed deglutitive upper esophageal sphincter relaxation in neurogenic dysphagia

Our aims were to examine the etiology and biomechanical properties of the nonrelaxing upper esophageal sphincter (UES) and the relationship between UES opening and failed relaxation. We examined the relationships among swallowed bolus volume, intrabolus pressure, sagittal UES diameter, the pharyngeal swallow response, and geniohyoid shortening in 18 patients with failed UES relaxation, 23 healthy aged controls, and 15 with Zenker's diverticulum. Etiology of failed UES relaxation was 56% medullary disease, 33% Parkinson's or extrapyramidal disease; and 11% idiopathic. Extent of UES opening ranged from absent to normal and correlated with preservation of the pharyngeal swallow response (P = 0.012) and geniohyoid shortening (P = 0.046). Intrabolus pressure was significantly greater compared with aged controls (P < 0.001) or Zenker's diverticulum (P < 0.001). The bolus volume-dependent increase in intrabolus pressure evident in controls was not observed in failed UES relaxation. The nonrelaxing UES therefore displays a constant loss of sphincter compliance throughout the full, and potentially normal, range of expansion during opening. Adequacy of UES opening is influenced by the degree of preservation of the pharyngeal swallow response and hyolaryngeal traction. In contrast, the stenotic UES displays a static loss of compliance, only apparent once the limit of sphincter expansion is reached.     

Deglutitive inhibition affects both esophageal peristaltic amplitude and shortening

Deglutitive inhibition attenuates ongoing esophageal contractions if swallows are separated by short time intervals. This study aimed to determine whether esophageal shortening, mediated by longitudinal muscle, was similarly affected. Eight healthy subjects with two distal esophageal segments demarcated by mucosal clips and manometric recording sites positioned within those segments underwent concurrent manometry and fluoroscopy. Peristaltic amplitude and change in distal segment lengths were quantified during single swallows, paired swallows separated by progressively prolonged intervals, and a series of rapid repetitive swallows. During grouped swallows, deglutitive inhibition with complete attenuation of both the manometric contraction and segment shortening was evident with short-interval swallows and rapid-sequence swallows. No inhibition of either was evident with long-interval pairs. With intermediate interswallow intervals, the occurrence and degree of deglutitive inhibition between peristaltic amplitude and segment shortening were closely correlated. Deglutitive inhibition affects both the longitudinal and circular muscle layers of the esophageal wall, and the occurrence of inhibition evident in one layer is strongly correlated with the other.     

The role of hiatus hernia in GERD

Increased esophageal acid exposure in gastroesophageal reflux disease has several potential causes, some related primarily to physiological dysfunction of the LES and others related to anatomic distortion of the gastroesophageal junction as occurs with hiatus hernia. One attractive feature of implicating hiatal hernias in the pathogenesis of reflux disease is that, like reflux disease, axial hernias become more common with age and obesity. However, the importance of hiatus hernia is obscured by imprecise definition and an all-or-none conceptualization that has led to wide variation in estimates of prevalence among normal or diseased populations. There are at least three potentially significant radiographic features of a hiatus hernia: axial length during distention, axial length at rest, and competence of the diaphragmatic hiatus. Although any or all of these features may be abnormal in a particular instance of hiatus hernia, each is of different functional significance. Grouping all abnormalities of the gastroesophageal junction as "hiatus hernia" without detailing the specifics of each case defies logic. Mechanistically, the gastroesophageal junction must protect against reflux both in static and dynamic conditions. During abrupt increases in intra-abdominal pressure, the crural diaphragm normally serves as a "second sphincter," and this mechanism is substantially impaired in individuals with a gaping hiatus. Large, non-reducing hernias also impair the process of esophageal emptying, thereby prolonging acid clearance time following a reflux event (especially while in the supine posture). These anatomically-determined functional impairments of the gastroesophageal junction lead to increased esophageal acid exposure. Thus, although hiatus hernia may or may not be an initiating factor at the inception of reflux disease, it clearly can act as a sustaining factor accounting for the frequently observed chronicity of the disease.     

Upper esophageal sphincter impedance as a marker of sphincter opening diameter

The measurement of the physical extent of opening of the upper esophageal sphincter (UES) during bolus swallowing has to date relied on videofluoroscopy. Theoretically luminal impedance measured during bolus flow should be influenced by luminal diameter. In this study, we measured the UES nadir impedance (lowest value of impedance) during bolus swallowing and assessed it as a potential correlate of UES diameter that can be determined nonradiologically. In 40 patients with dysphagia, bolus swallowing of liquids, semisolids, and solids was recorded with manometry, impedance, and videofluoroscopy. During swallows, the UES opening diameter (in the lateral fluoroscopic view) was measured and compared with automated impedance manometry (AIM)-derived swallow function variables and UES nadir impedance as well as high-resolution manometry-derived UES relaxation pressure variables. Of all measured variables, UES nadir impedance was the most strongly correlated with UES opening diameter. Narrower diameter correlated with higher impedance (r = -0.478, P < 0.001). Patients with <10 mm, 10-14 mm (normal), and ≥ 15 mm UES diameter had average UES nadir impedances of 498 ± 39 Ohms, 369 ± 31 Ohms, and 293 ± 17 Ohms, respectively (ANOVA P = 0.005). A higher swallow risk index, indicative of poor pharyngeal swallow function, was associated with narrower UES diameter and higher UES nadir impedance during swallowing. In contrast, UES relaxation pressure variables were not significantly altered in relation to UES diameter. We concluded that the UES nadir impedance correlates with opening diameter of the UES during bolus flow. This variable, when combined with other pharyngeal AIM analysis variables, may allow characterization of the pathophysiology of swallowing dysfunction.     

The mechanical basis of impaired esophageal emptying postfundoplication

Fundoplication (FP) efficacy is a trade-off between protection against reflux and postoperative dysphagia from the surgically altered mechanical balance within the esophagogastric segment. The purpose of the study was to contrast quantitatively the mechanical balance between normal and post-FP esophageal emptying. Physiological data were combined with mathematical models based on the laws of mechanics. Seven normal controls (NC) and seven post-FP patients underwent concurrent manometry and fluoroscopy. Temporal changes in geometry of the distal bolus cavity and hiatal canal, and cavity-driving pressure were quantified during emptying. Mathematical models were developed to couple cavity pressure to hiatal geometry and esophageal emptying and to determine cavity muscle tone. We found that the average length of the hiatal canal post-FP was twice that of NC; reduction of hiatal radius was not significant. All esophageal emptying events post-FP were incomplete (51% retention); there was no significant difference in the period of emptying between NC and post-FP, and average emptying rates were 40% lower post-FP. The model predicted three distinct phases during esophageal emptying: hiatal opening (phase I), a quasi-steady period (phase II), and final emptying (phase III). A rapid increase in muscle tone and driving pressure forced normal hiatal opening. Post-FP there was a severe impairment of cavity muscle tone causing deficient hiatal opening and flow and bolus retention. We conclude that impaired esophageal emptying post-FP follows from the inability of distal esophageal muscle to generate necessary tone rapidly. Immobilization of the intrinsic sphincter by the surgical procedure may contribute to this deficiency, impaired emptying, and possibly, dysphagia.     

Evidence for a peripheral mechanism of esophagocrural diaphragm inhibitory reflex in cats

The esophagogastric junction (EGJ) is guarded by two sphincters, a smooth muscle lower esophageal sphincter (LES) and a skeletal muscle crural diaphragm. These two sphincters relax simultaneously under certain physiological conditions, i.e., swallowing, belching, vomiting, transient LES relaxation, and esophageal distension. Esophageal distension-induced crural diaphragm relaxation is mediated through vagal afferents that are thought to exert inhibitory influence on the central mechanism (brain stem) of crural diaphragm contraction. We conducted studies in 10 cats to determine whether a mechanism of crural diaphragm relaxation was located at the level of the neuromuscular junction and/or muscle. Stimulation of the crural diaphragm neuromuscular junction through 1) the electrodes implanted in the muscle and 2) the bilateral phrenic nerve resulted in an increase in EGJ pressure. Nicotinic receptor blockade (pancuronium, 0.2 mg/kg) abolished the EGJ pressure increase caused by electrical stimulation of the neuromuscular junction. Esophageal distension and bolus-induced secondary esophageal peristalsis caused relaxation of the EGJ during the stimulation of the neuromuscular junction. Bilateral phrenicotomy and vagotomy had no influence on this relaxation. These data suggest the existence of a peripheral mechanism of crural diaphragm inhibition. This peripheral inhibitory mechanism may reside at the level of either the neuromuscular junction or the skeletal muscle.