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Keywords:

  • esophageal distension and contraction;
  • esophageal inhibition;
  • high frequency intraluminal ultrasonography

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Author Contributions
  9. Competing Interests
  10. References

Background  Current understanding is that swallow induces simultaneous inhibition of the entire esophagus followed by a sequential wave of contraction (peristalsis). We observed a pattern of luminal distension preceding contraction which suggested that inhibition may also traverses in a peristaltic fashion. Our aim is to determine the relationship between contraction and luminal distension during bolus transport.

Methods  Eight subjects using two solid-state pressure and two ultrasound (US) transducers were studied. Synchronous pressure and US images were obtained with wet swallows and after edrophonium and atropine. Luminal cross-sectional area (CSA) at 2 cm and 12 cm above the lower esophageal sphincter (LES) were recorded. Relationship between pressure and CSA at each site, propagation velocity of peak pressure and peak distension waves were determined. Fluoroscopy coupled with manometry was also performed in five normal subjects.

Key Results  Esophageal distension precedes contraction wave at both-recorded sites. During distension, esophageal pressure remains constant while luminal CSA increases significantly. The onset and the peak of distension wave traverses in a peristaltic fashion between both sites. A tight coupling exists between the peak distension and peak contraction waves with similar velocities (3.7 cm s−1 and 3.6 cm s−1) of propagation. The degree of distension is greater at 2 cm compared to 12 cm. Atropine and edrophonium reduced and increased the contraction pressure respectively, without affecting the distension wave. Fluoroscopic study confirmed that the wave of distension traverses the esophagus in a peristaltic fashion.

Conclusions & Inferences  Distension and contraction waves are tightly coupled to each other and both traverse in a peristaltic fashion.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Author Contributions
  9. Competing Interests
  10. References

Key elements of the peristaltic reflex throughout the gastrointestinal tract are an initial inhibition followed by contraction. While circular muscle contraction can be recorded relatively easily using intraluminal pressure recording technique, esophageal inhibition can only be studied using indirect techniques, especially in humans. Investigators have utilized multiple swallows at closely spaced intervals to show that each swallow induces initial inhibition along the entire length of the esophagus.1–3 Sifrim et al. studied esophageal inhibition using artificial pressure zones that were created by inflation of two small balloons in the esophagus. Using two high-pressure zones at two levels in the distal esophagus they observed that a swallow causes simultaneous inhibition of the both high-pressure zones.4 Based on the above and other studies, the current thinking is that each deglutition induces simultaneous inhibition along the entire length of esophagus that is followed by sequential (peristaltic) contraction.5

Using high frequency intraluminal ultrasound (HFIUS) imaging technique, we observed a peristaltic pattern of esophageal luminal distension, which precedes the contraction wave. The latter could suggest that similar to the contraction, the wave of inhibition may also traverse the esophagus in a peristaltic fashion. The aim of our study was to determine the relationship between luminal distension (surrogate marker of inhibition) and intra-luminal pressure (marker of contraction) during swallow induced bolus transport in the distal esophagus, using HFIUS imaging and fluoroscopy techniques. Furthermore, we studied the effects of atropine and edrophonium on the swallow-induced distension and contractions in the esophagus.

Materials and methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Author Contributions
  9. Competing Interests
  10. References

Study comprised two different protocols: in the first protocol, simultaneous HFIUS imaging and pressures were recorded at 2 cm and 12 cm sites above the lower esophageal sphincter (LES). The Human Investigation Committee of the University of California San Diego approved the study protocol. The second part of the study, simultaneous fluoroscopy and manometry was conducted in Brazil, following approval by the ‘Ethics Research Committee of Rio de Janeiro Federal University’. Written informed consent was obtained from each subject prior to each study.

High frequency intraluminal ultrasound and manometry

Subjects and study protocol  Eight healthy volunteers (three men, mean age: 34.7 ± 3.2 years) with no history of gastrointestinal disease were included. After an overnight fast, recordings were obtained in recumbent supine position using a special custom made catheter assembly. The latter consisted of two HFIUS catheters and two solid-state pressure transducers catheters (Millar Mikro-tip; Millar Instruments, Houston, TX, USA). Each US catheter (distal transducer: 30 MHz; MicroRail Cardiovascular Imaging Systems; Sunnyvale, CA, USA and proximal transducer: 20 MHz; Volcano Corporation, Rancho Cordova, CA, USA) was taped together with one Millar probe in such a fashion that the US and pressure transducer were located at the same axial level. The two US and two pressure transducer catheter sets were attached to each other in such a fashion that the US and pressure transducers were spaced 10 cm apart.

The nasal cavity and oropharynx were anesthetized using 1% lidocaine gel or 1% benzocaine spray. The US and pressure transducer catheter assembly was introduced into the stomach and a station pull-through technique was used to locate the LES. Recordings were performed with the pressure and US transducers located at the 2 cm and 12 cm above the LES. Five swallows of 5 mL water, and five swallows of 10 mL water at room temperature were performed under each of the following conditions: control period, after intravenous (i.v.) injection of edrophonium (80 μg kg−1), and after i.v. atropine (5 μg kg−1). Atropine injection was performed at least 5 min after edrophonium administration. Ten minutes were allowed to elapse after atropine injection and then water swallows were performed. Subjects were asked to: (i) refrain from swallowing for 30 s in between each water swallow and (ii) exhale before swallowing and hold their breath for approximately 15 s to minimize the effects of breathing on the esophageal and intrabolus pressure.

Pressures were recorded on a computer through Polygraph ID and Polygram 98 (Medtronic Synectics, Shoreview, MN, USA). Ultrasound images were recorded on VHS tape recorders interfaced to the HP Sonos 100 machine (Hewlett-Packard, Watertown, MA, USA) and an In-Vision Gold machine (Volcano Corporation, Rancho Cordova, CA, USA). Pressure and US recordings were synchronized using a time code device (Thalaner Electronics; Ann Arbor, MI, USA) that encoded the analog time clock on the video images and a marker on the polygraph at a resolution of one hundredth of a second.

Data analysis

Ultrasound images were digitized at a rate of 29.97 Hz using a video capture card (Pinnacle Express; Pinnacle, Mountain View, CA, USA) interfaced to a personal computer (PC) using Adobe Premiere 6.0 program (Adobe Systems; Mountain View, CA, USA). Ultrasound images, captured in an AVI format were exported as two-dimensional bitmap image files (B-mode) and then converted into sixteen equi-spaced (22.5°) M-mode files using a proprietary program. M-mode image was analyzed using a commercially available image analysis-software package (Sigma Scan Pro; Jandel Scientific, San Rafael, CA, USA) and the esophageal lumen edges were manually drawn in each of the sixteen M-modes. Lumen cross-section area (CSA) was calculated using a methodology created and validated in our laboratory.

The following variables were analyzed from each swallow: maximal amplitude and duration of distension and contraction, time interval between proximal and distal distension and contraction waves (both onset and peak), velocity of onset and peak propagation of distension and contraction waves, and intrabolus pressure at maximal distension (intrabolus pressure relative to baseline end-expiratory pressure before each swallow). We also performed correlations between maximal distension and peak pressure amplitude for each swallows, between distension and contraction peak velocity of propagation and between intrabolus pressure and peak distension with 5 mL swallows.

Data comparisons were performed using three grouping variables: swallow volume (5 mL vs 10 mL), esophageal location (proximal vs distal) and interventions (baseline, edrophonium and atropine).

Methodology and validation of M-mode lumen CSA calculation

In each M-mode image, the radial distance between the center of the image (US catheter location) and the outer luminal edge was determined. Area of the triangular region encompassed by the two adjacent radial lines was calculated (area = R1 × R2 × sin α × 0.5, where R1 and R2 are two adjacent radius and α = 22.5° is the angle between the two radial lines). Total lumen area was obtained from the sum of the 16 areas. The validation of the luminal measurement was performed by comparing the results from B-mode and M-mode images in two phantom models of the esophagus and then in one swallow event from three subjects. Two phantom models were created: the first one consisting of 120 circular shaped images and the second one comprised of 230 images variable elliptical shape and eccentric catheter position within the lumen. In both models, lumen CSA was first determined in the B-mode images and then correlated with M-mode findings. Linear regression analysis showed an excellent correlation of area measurements with r2 values of 0.9933 and 0.9997, respectively. For further validation, the same technique was used to analyze US images obtained 2 cm above LES after a 5 mL water swallow in three normal volunteers for 10 s following each swallow event. Lumen CSA derived from B-modes was correlated with corresponding M-mode measurements and yielded r2 values of 0.97 to 0.99.

Simultaneous manometry and fluoroscopy

Subjects and study protocol  Simultaneous manometry and X-ray fluoroscopy were performed in five healthy volunteers (two men, 26 ± 4 years). None of the subjects was taking medications that could affect gastrointestinal motility. After overnight fast and topical anesthesia of the nose, a manometry catheter with four solid-state pressure sensors, 5 cm apart was introduced into the stomach. The study was performed in supine position with pressure sensors located at 2, 7, 12 and 17 cm above the LES. Ten swallows of 10 mL, 1 : 1 diluted barium, 30 s apart were performed. The first five swallows were recorded with the subjects at 30° left anterior oblique position and the remaining five at 60° right anterior oblique position. Images were recorded on a DVD recorder (Phillips do Brazil, Sao Paulo, Brazil) at 29.97 fps and then converted to a PC as AVI movies. Pressure and fluoroscopy images were synchronized using a time code device (Horita, Mission Viejo, CA, USA) that encoded the analog time clock on the video images at a resolution of one-hundredth of a second.

Data analysis  X-ray images, captured in AVI format were exported as two-dimensional bitmap image files (B-mode) using Adobe Premiere 6.0 program (Adobe Systems, San Jose, CA, USA). Two-dimensional bitmap images for each swallow were analyzed using an image analysis-software package (Image J; National Institute of Health, Bethesda, MD, USA) and video intensity was obtained from three zones of interest, each one located at pressure sensors at 2, 7 and 12 cm above LES. Video intensity (VI), a measurement of the amount of contrast at a given location was used as a surrogate marker of esophageal distension. Video intensity and pressure data were temporally aligned using the time encoder and plotted together.

Following measurements were analyzed from each swallow: time interval between the proximal and distal distension and contraction waves (both onset and peak), velocity of onset and peak propagation of distension and contraction waves, and intrabolus pressure at maximal distension (increase of intrabolus pressure relative to baseline end-expiratory pressure before each swallow).

Statistical analysis

Data are shown as mean ± SEM. Kolmogorov–Smirnov test was used to verify each variables normal distribution. Student’s t-test was used for parametric and Kruskal–Wallis test for non-parametric data comparisons. A P-value <0.05 indicated statistical significance.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Author Contributions
  9. Competing Interests
  10. References

Simultaneous ultrasound imaging and manometry

Fifty percent of 5 mL and 10 mL recorded swallows were randomly selected for the analysis. The number of swallow-induced events analyzed in the control, edrophonium and atropine condition was 30, 30 and 26, respectively (atropine was not administered in one subject).

Relationship between bolus pressure and luminal cross sectional area  Following each swallow and at esophageal site, US images show a period of luminal distension followed by a period of luminal closure (Fig. 1). The period of luminal closure can be divided into phase 1 and phase 2. The phase 1 starts from a fully distended esophagus with the onset of luminal collapse, to the first complete collapse of esophageal lumen over the catheter. Phase 2 starts from the end of phase 1 to the end of manometric contraction wave. During the entire phase 2, the lumen size does not change (equal to the size of catheter) but there is an increase in the thickness of muscularis propria. Our earlier studies show that the circular and longitudinal muscles start to contract at the onset of lumen collapse or phase 1 and stay contracted until a short time after the manometric pressure wave has passed.6 We focused on the period of luminal distension i.e. between the onsets of increase in the lumen CSA to the peak CSA because this period ‘likely’ represents the relaxation period. Esophageal pressure remains relatively constant during the luminal distension phase (known as intrabolus pressure), both at 2 cm and 12 cm above the LES while there is large increase in the luminal CSA. Figure 2 shows the bolus pressure and change in CSA values during this period. The intrabolus pressure was slightly (1–2 mmHg) higher at the 2 cm as compared to the 12 cm site but the peak CSA at the 2 cm level was more than two times compared with 12 cm level, suggesting a greater degree of relaxation at the 2 cm site. The duration of distension wave was longer at the 2 cm site as compared to the 10 cm site and increased significantly with the increase in the bolus volume.

image

Figure 1.  M-mode images from 12 cm and 2 cm sites in the esophagus with corresponding lumen CSA-pressure plots. The 12 cm M-mode shows the onset and peak distension taking place before onset and peak distension in the distal M-mode. Corresponding pressure and lumen CSA plots are shown below each M-mode image.

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image

Figure 2.  (A) Mean intrabolus pressures at maximal distension at 12 cm and 2 cm above the LES with 5 mL and 10 mL swallows at baseline (BSL), edrophonium (EDR) and atropine (ATR). Note that the bolus pressures are slightly but significantly different between two esophageal sites and with two different volumes. Also, note that atropine and edrophonium do not affect the intrabolus pressure. (*P < 0.05) (B) Peak lumen cross sectional area (CSA) at 12 cm and 2 cm above the LES following 5 mL and 10 mL swallows before and after edrophonium and atropine. Peak CSA was significantly higher at the 2 cm site as compared to 12 cm site for 5 mL and 10 mL swallows, and for 10 mL swallows compared to 5 mL swallows in the distal esophagus. Note that edrophonium and atropine did not affect the peak CSA for either 5 mL or 10 mL swallows (*P = 0.0001; #P = 0.016).

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Increase in swallowed bolus volume increased intrabolus pressure slightly but significantly. The peak CSA was also significantly higher with 10 mL as compared to 5 mL. (Fig. 2B) Atropine and edrophonium had no effect on the intrabolus pressure and the peak CSA (Fig. 2A, B). On the other hand, atropine caused a significant decrease in the manometric contraction amplitude and edrophonium resulted in significant increase in the amplitude of contraction pressure (Fig. 3).

image

Figure 3.  Contraction wave amplitudes at 2 cm and 12 cm above LES at baseline, before and after edrophonium and atropine for 5 mL and 10 mL swallows. Note that pressures are significantly higher at 12 cm for 5 mL swallows after edrophonium and significantly lower at 2 cm and 12 cm and for 5 and 10 mL swallows after atropine (*P < 0.05).

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Relationship between distension and contraction waves in the esophagus  To demonstrate the relationship between peak esophageal contraction and corresponding maximal distension, at each level, a linear regression analysis was performed. The results disclosed a very poor correlation, with a large range of R values (−0.63 to 0.84 for 5 mL at 12 cm, −0.79 to 0.76 for 5 mL at 2 cm, −0.99 to 0.74 for 10 mL at 12 cm and −0.63 to 0.84 for 10 mL at 2 cm) with different slopes and interception points. The above results suggest that the amplitude of contraction does not determine the amplitude of distension of the esophagus.

Velocity of propagation of distension and contraction waves  The onset and the peak of distension waves show a time lag between the 12 cm and the 2 cm esophageal sites with both occurring first at the 12 cm site. The mean time lag for the onset of distension between 12 cm and 2 cm sites was 1.3 ± 0.17 s for 5 mL swallows and 1.2 ± 0.25 s for 10 mL swallows (Fig. 4A), with velocities of propagation of 13.2 ± 2 cm s−1 and 20.9 ± 3.7 cm s−1, respectively (= 0.07) (Fig. 4B). Along the same lines, the mean time lag for peak distension between the 12 cm and 2 cm sites was 2.7 ± 0.18 s for the 5 mL swallows and 2.8 ± 0.21 s for 10 mL swallows (Fig. 4A), with velocities of propagation of 6.3 ± 2.4 cm s−1 and 4.1 ± 0.33 cm s−1, respectively (= 0.38) (Fig. 4B).

image

Figure 4.  (A) Time lag between the onset and peak of distension and contraction waves at 2 cm and 12 cm sites for 5 mL and 10 mL swallows. Note that similar to contraction, the onset as well as the peak of distension waves are peristaltic. (B) Velocity of propagation of distension and contraction waves between 2 cm and 12 cm sites for 5 mL swallow and the effects of atropine and edrophonium. Note that contraction peak velocity was significantly reduced after edrophonium and increased after atropine. Edophonium and atropine did not affect velocity of onset and peak of distension wave (*P < 0.05).

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The interval between peak distension and pressure at 2 cm and 12 cm was of 2.5 ± 0.1 s and 2.6 ± 0.1 s for 5 mL and of 2.8 ± 0.1 s and 3.1 ± 0.2 s for 10 mL swallows, respectively. After edrophonium administration these values increased at 2 cm and 12 cm significantly to 4.1 ± 0.5 s and 3.5 ± 0.3 s for 5 mL swallows and to 3.1 ± 0.2 s and 3.7 ± 0.2 s for 10 mL swallows, respectively (< 0.05 for all comparisons). The velocities of distension after atropine injection in 5 mL swallows were of 13 ± 1.67 cm s−1 and 5.34 ± 1.35 cm s−1 for onset and peak distension, respectively, values not significantly different from the baseline (= 0.24 and = 0.7, respectively).

Pressure amplitudes were significantly reduced in both the proximal and the distal esophagus after atropine for both 5 mL and 10 mL swallows as compared to the baseline values (Fig. 4A). On the other hand, pressure amplitudes were significantly increased at the 12 cm after edrophonium, for both 5 mL and 10 mL swallows when compared to baseline values. (Fig. 3) The velocities of distension propagation after edrophonium injection in 5 mL swallows were of 16.8 ± 3.2 cm s−1 and 3.4 ± 0.7 cm s−1 for onset and peak distension, respectively, values not significantly different from baseline (= 0.3 and = 0.25, respectively). On the other hand, the velocity of contraction wave was significantly reduced by edrophonium and increased by atropine (Fig. 4B).

Simultaneous manometry and fluoroscopy

A total of fifteen (three from each subject) swallows were analyzed for this part of the study. Intrabolus pressure remained relatively constant during the distension phase of swallow at both 12 cm and 2 cm sites. For the 12 cm site, the mean intrabolus pressure at maximal distension (maximal video intensity value) during baseline was 14.0 ± 0.7 mmHg and for the 2 cm site the corresponding value was 13.3 ± 0.8 mmHg (Fig. 5A, B). Fluoroscopic and manometry recording shows that the onset and the peak of bolus concentration and contraction waves in the distal esophagus are sequential, i.e. peristaltic. The time lag for the onset and peak of bolus concentration as recorded by the change in the video-intensity signal between the 2 cm and 12 cm sites was 1.5 ± 0.3 s and of 4.1 ± 0.5 s, respectively. The time lag between the two esophageal sites for the onset and peak of contraction was 3.0 ± 0.4 s and of 3.5 ± 0.5 s, respectively (Fig. 5B).

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Figure 5.  (A) Fluoroscopy and pressure recording from one subject: video-intensity was determined from the fluoroscopy images (see methods for detail) and temporally aligned with the changes in video-intensity plots at 2 cm, 7 cm and 12 cm above LES. Changes in video-intensity (a marker of esophageal distension) precedes the contraction wave (pressure wave), both the onset as well as the peak of distension, similar to contraction wave, move along the length of the esophagus in a peristaltic fashion. (B) Time lag between the onset and peak of distension (from the video intensity (VI) obtained from the fluoroscopic images), and onset and peak of contraction (from pressure record) following 10 mL barium swallows. Note that similar to contraction wave, both the onset as well as the peak of distension waves are peristaltic.

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Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Author Contributions
  9. Competing Interests
  10. References

In brief, our data show several important findings: (i) Following swallow, and at each esophageal site, there is a large increase in the luminal CSA while the esophageal or intrabolus pressure remains relatively constant. The increase in luminal CSA is significantly greater at the 2 cm as compared to the 10 cm site. (ii) The onset and the peak of distension wave traverse the esophagus in a peristaltic fashion. (iii) There is no relationship between the amplitude of contraction and the amplitude of distension wave. (iv) Atropine and edrophonium that decrease and increase the contraction amplitude respectively have no effect on the distension amplitude. (v) Fluoroscopy findings confirm our observation recorded by the US image recording technique.

Initial inhibition and subsequent contraction are essential elements of the peristaltic reflex. Christensen studied muscle strip from the different regions of the opossum esophagus and observed that the electrical stimulation induces muscle contraction following an initial latency period.7 The latency period was longer in the distal as compared to proximal esophagus, suggesting the mechanism of peristalsis to be located at the peripheral level. Decktor recorded resting membrane potential of the isolated esophageal circular muscle strips and found a decrease in the resting membrane potential (hyperpolarization) during the latency period followed by the depolarization associated with spike potentials during the contraction periods.8 Hyperpolarization, which represents muscle inhibition, was longer in the distal as compared to proximal esophagus. Rattan conducted an in vitro study of electrical and mechanical events in the opossum esophagus and observed that a swallow induces an initial period of hyperpolarization followed by depolarization and the latter was associated with a contraction wave.9 There is no correlate of hyperpolarization in the pressure recording because even though esophagus has a resting tone10 but unlike LES there is no resting esophageal pressure. Whether hyperpolarization traverses the esophagus in a peristaltic fashion has never been studied. As there are no pressure changes in the esophagus during hyperpolarization, it is relatively difficult to study the esophageal inhibition.

High frequency intraluminal US imaging allows direct visualization and calculation of the luminal CSA during bolus transport and therefore is ideally suited to record changes in the luminal CSA with the change in pressure or in other words changes in esophageal wall compliance. A large increase in the luminal CSA for a constant esophageal or intrabolus pressure observed in our study implies an increase in the esophageal wall compliance and the latter most likely represents relaxation of the esophageal wall (or muscles of esophagus). Nicosia et al. also recorded esophageal distension prior to contraction at one site in the esophagus and close inspection of their graph shows that the esophageal pressure does not change significantly during the period of distension.11 We used two HFIUS probes to record peristaltic progression of the luminal distension and found that following a swallow; both the onset and peak of distension traverse the esophagus in a peristaltic fashion. The latter implies that similar to the contraction wave, the wave of distension also traverse the esophagus in a peristaltic fashion.

To confirm observations made from the HFIUS images, we also performed a fluoroscopic study coupled with manometry. We expected to see a globular distension of the esophagus traversing along the length of esophagus in a peristaltic fashion; however, that was not obvious on the fluoroscopic images. The reason is that the fluoroscopic images are record in one lateral plane and the US images visualize transverse plane or the luminal CSA of the esophagus. Therefore, instead of looking at the dimension of the esophagus we measured the video intensity signal, a measure of the amount of contrast at a single location in the esophagus. The video-intensity results are identical to the HFIUS results, i.e., the onset and peak of video-intensity signal traverse the esophagus a peristaltic fashion and the peak signal is located just distal to the onset of esophageal contractions wave. Pouderoux et al. studied esophageal bolus transport with ultrafast CT scanner and Fig. 4 of their paper, similar to our finding, suggests peristaltic progression of distension along the length of the esophagus.12

Reason for studying distension in our experiment was that it may be a surrogate marker of esophageal inhibition. Our reasoning is that the function of initial inhibition in the peristaltic reflex is bolus accommodation. We observed increasing distension in the presence of a constant esophageal pressure, which we interpret as increase in the compliance of esophageal wall. The latter in our experimental setting can only be explained on the basis of active relaxation or inhibition of the esophageal wall, as we studied subjects in the supine position and gravity did not play any role. Our study shows that the luminal CSA is significantly larger at the 2 cm as compared to the 12 cm site in the esophagus, even though intrabolus pressure was only slightly higher at the 2 cm site. The latter implies either the lower esophagus is relatively more compliant than the upper esophagus or there is a greater degree of esophageal relaxation at the 2 cm site. We favor the latter because other studies have found greater degree of nitrinergic innervation of the distal as compared to the proximal esophagus.13,14 Sifrim et al. who studied esophageal inhibition in humans by creating an artificial high pressure zones with a small balloon4,15 found results different from ours. They observed that each swallow results in drop in pressure (relaxation) of the high pressure zone. The duration of relaxation was longer in the distal as compared to proximal esophagus but the onset of relaxation at the two-recorded sites was simultaneous. The difference between our study and Sifrim study may be related to the lower sensitivity of their recording technique to detect onset of relaxation.

We observed that there is no correlation between the contraction amplitude and the distension amplitude in the esophagus. Furthermore, atropine and edrophonium that decreased and increased the contraction amplitude, respectively, had no effect on the distension amplitude. Close inspection of US images shows that during contraction the esophageal lumen is completely closed and the peak pressures in the contracted segment is located several centimeters proximal to the peak distension and therefore it should not be surprising that the contraction amplitude does not affect the distension. The distended segment is under the influence of the intrabolus pressure. As atropine and edrophonium had no effect on the bolus pressure the distension amplitude was not affected by these agents. The determinant forces of intrabolus pressure in normal subjects were recently reviewed by Gosh et al., using high resolution manometry and fluoroscopy.16 The main determinants of intrabolus pressure are peristaltic function and esophagogastric junction compliance. An important factor not considered in their study is the esophageal wall compliance that would be related to inhibition function and passive properties of esophageal wall. Hypertrophy of esophageal muscles, seen in motor disorders of the esophagus,17,18 may also be another important determinant of intrabolus pressure.

We do not imply that at any given time during peristalsis esophageal inhibition only occurs at one location (point location) and that this point traverses in a peristaltic fashion. At any given instance during peristalsis a segment of the esophagus is contracted and pressures in the contracted segment are distributed in the form of a bell-shaped curve. We propose that similar to contraction, at any given time during peristalsis, a segment of the esophagus is inhibited and this segment traverses in front of the contraction segment. The peak distension (that represents the site of maximal inhibition) is located just distal to the site of the onset of esophageal contraction and few centimeters distal to the site of peak contraction but there is a segment of the esophagus of varying length, caudal to the site of peak distension that is also inhibited (Fig. 6). Various manometry techniques, including the ‘new kid on the block’ high-resolution manometery16 record only the contraction phase of peristalsis and motor disorders of the esophagus are classified based on the contraction abnormalities of the esophagus. Studies by Sifrim and others show that inhibition is impaired in patients with diffuse esophageal spasm and possibly other motor disorders of the esophagus.15 Future studies using techniques mentioned in the current study may investigate the abnormalities of waves of distension of the esophagus as a cause of dysphagia, especially in those patients where esophageal manometry and impedance studies are normal.

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Figure 6.  Schematic of contraction and distension during swallow induced peristalsis. Note that the pressure and muscle cross sectional area (MCSA), surrogate markers of circular and longitudinal muscle contractions respectively, precede distension that marches distally in front of the onset of contraction wave in a peristaltic fashion.

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Acknowledgments

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Author Contributions
  9. Competing Interests
  10. References

This study was funded by US National Institute of Health grant support RO1-DK060733 to Dr. Ravinder K. Mittal. Authors thank Dr Petr Krysl PhD, Professor of Engineering in the Department of Structural Engineering, Jacobs School of Engineering, University of California, San Diego for assistance.

Author Contributions

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Author Contributions
  9. Competing Interests
  10. References

RKM and VB designed the research study; LA and AB conducted the research protocol; LA, AB and AH analyzed the data and LA and RKM wrote the paper.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Author Contributions
  9. Competing Interests
  10. References
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