Title: Asynchrony Between the Circular and the Longitudinal Muscle Contraction in Patients With Nutcracker Esophagus
Abstract: Background & Aims: The increases in intraluminal pressure and muscle cross-sectional area (CSA) during esophageal contraction are markers of circular and longitudinal muscle contractions. The goal of our study was to determine temporal synchrony between circular and longitudinal muscle contraction in healthy subjects and patients with nutcracker esophagus. Methods: Pressure and high-frequency intraluminal ultrasound (HFIUS) images were recorded simultaneously in healthy subjects and patients with nutcracker esophagus at 2 and 10 cm above the lower esophageal sphincter during wet swallow. HFIUS images were digitized and analyzed for the muscle CSA. The time interval (δ-t) between the peak muscle CSA and the peak pressure was determined. Results: In healthy subjects, a close temporal correlation existed between the peak contraction pressure and the peak muscle CSA with a maximum δ-t of 0.5 seconds at the 2- and 10-cm levels (0–0.5 seconds). On the other hand, the patient group had a median δ-t of 1.25 seconds (0.75–3.5 seconds) at the 2-cm level and 0.75 seconds (0–2.0 seconds) at the 10-cm level. Ninety-eight of 103 contractions in patients showed a δ-t >0.5 seconds. There was a significant correlation between δ-t and the amplitude of pressure wave, the duration of pressure wave, and the peak muscle CSA. The duration of pressure wave but not the duration of CSA wave was longer in patients with nutcracker esophagus as compared with healthy subjects. Conclusions: Patients with nutcracker esophagus show temporal asynchrony between the contractions of circular and longitudinal muscle layers. Background & Aims: The increases in intraluminal pressure and muscle cross-sectional area (CSA) during esophageal contraction are markers of circular and longitudinal muscle contractions. The goal of our study was to determine temporal synchrony between circular and longitudinal muscle contraction in healthy subjects and patients with nutcracker esophagus. Methods: Pressure and high-frequency intraluminal ultrasound (HFIUS) images were recorded simultaneously in healthy subjects and patients with nutcracker esophagus at 2 and 10 cm above the lower esophageal sphincter during wet swallow. HFIUS images were digitized and analyzed for the muscle CSA. The time interval (δ-t) between the peak muscle CSA and the peak pressure was determined. Results: In healthy subjects, a close temporal correlation existed between the peak contraction pressure and the peak muscle CSA with a maximum δ-t of 0.5 seconds at the 2- and 10-cm levels (0–0.5 seconds). On the other hand, the patient group had a median δ-t of 1.25 seconds (0.75–3.5 seconds) at the 2-cm level and 0.75 seconds (0–2.0 seconds) at the 10-cm level. Ninety-eight of 103 contractions in patients showed a δ-t >0.5 seconds. There was a significant correlation between δ-t and the amplitude of pressure wave, the duration of pressure wave, and the peak muscle CSA. The duration of pressure wave but not the duration of CSA wave was longer in patients with nutcracker esophagus as compared with healthy subjects. Conclusions: Patients with nutcracker esophagus show temporal asynchrony between the contractions of circular and longitudinal muscle layers. Intraluminal pressure and high-frequency intraluminal ultrasound (HFIUS) image analysis provide a unique opportunity to study the relationship between the contractions of the 2 muscle layers (ie, the circular and the longitudinal muscles) of the esophagus. Intraluminal pressure is a marker of the circular muscle contraction. On the other hand, the change in the muscle cross-sectional area (CSA) as seen on HFIUS images is a marker of the longitudinal muscle contraction of the esophagus.1Miller L.S. Liu J. Colizzo F.P. Ter H. Marzano J. Barbarevech C. Helwig K. Leung L. Goldberg B.B. Correlation of high-frequency esophageal ultrasonography and manometry in the study of esophageal motility.Gastroenterology. 1995; 109: 832-837Abstract Full Text PDF PubMed Scopus (70) Google Scholar, 2Nicosia M.A. Brasseur J.G. Liu J. Miller L.S. Local longitudinal muscle shortening of the human esophagus from high-frequency ultrasonography.Am J Physiol Gastrointest Liver Physiol. 2001; 281: G1022-G1033PubMed Google Scholar Several studies show that there is a close temporal correlation between the contraction of 2 muscle layers. Whether the onset of contraction of 2 muscle layers occurs at the same time in healthy subjects is debatable, but there is general consensus that the contraction of the 2 layers peaks at the same time during swallow-induced and distention-induced esophageal contractions in healthy subjects.1Miller L.S. Liu J. Colizzo F.P. Ter H. Marzano J. Barbarevech C. Helwig K. Leung L. Goldberg B.B. Correlation of high-frequency esophageal ultrasonography and manometry in the study of esophageal motility.Gastroenterology. 1995; 109: 832-837Abstract Full Text PDF PubMed Scopus (70) Google Scholar, 2Nicosia M.A. Brasseur J.G. Liu J. Miller L.S. Local longitudinal muscle shortening of the human esophagus from high-frequency ultrasonography.Am J Physiol Gastrointest Liver Physiol. 2001; 281: G1022-G1033PubMed Google Scholar, 3Pehlivanov N. Liu J. Kassab G.S. Puckett J.L. Mittal R.K. Relationship between esophageal muscle thickness and intraluminal pressure an ultrasonographic study.Am J Physiol. 2001; 280: 1093-1098Google Scholar, 4Taniguchi D.K. Martin R.W. Trowers E.A. Dennis M.B. Odegaard S. Silverstein F.E. Change an esophageal wall layer during motility measurement with a new miniature ultrasound device.Gastrointest Endosc. 1993; 39: 146-152Abstract Full Text PDF PubMed Scopus (29) Google Scholar, 5Yamamoto Y. Liu J. Smith T.K. Mittal R.K. Distension related responses in the circular and longitudinal muscles of the esophagus an ultrasonographic study.Am J Physiol Gastrointest Liver Physiol. 1998; 275: G805-G811Google Scholar Visual inspection of the simultaneously recorded HFIUS images and manometry suggested that there is an asynchrony between the changes in the muscle thickness and pressure waves during swallow-induced peristalsis in patients with nutcracker esophagus. Therefore, the goal of our study was to study the temporal synchrony between the circular and the longitudinal muscle contraction during swallow-induced peristalsis in healthy subjects and patients with nutcracker esophagus in a systematic fashion. Our findings indicate that, unlike in healthy subjects, there is a temporal disassociation between the contractions of 2 muscle layers in patients with nutcracker esophagus leading to asynchronous contraction. Ten patients with nutcracker esophagus (5 men and 5 women; mean age, 51 ± 8 years) and 5 healthy volunteers (3 men and 2 women; mean age, 34 ± 10 years) were studied. Nutcracker esophagus was diagnosed when the mean contraction amplitude of the 10 swallow-induced peristaltic events at any one recording site in the esophagus exceeded 180 mm Hg and the contraction waves were peristaltic.6Pehlivanov N. Liu J. Kassabe G. Mittal R.K. Relationship between muscle thickness and pressure in patients with spastic motor disorders of the esophagus.Am J Physiol Gastrointest Liver Physiol. 2002; 282: G910-G916Google Scholar The human investigation committees of the University of California San Diego approved the study protocol, and informed consent was obtained from each subject before the study. After an overnight fast, recordings were obtained with the subjects in the right recumbent position. An 8-lumen manometry catheter (Dentsleeve Pty Ltd, Wayville, Australia) with 4 circumferentially placed side holes, located 2 mm from the distal end, in conjunction with an intravascular ultrasound (US) catheter was used to record pressure and US images simultaneously (Figure 1). A 30-MHz, 3.2-F, MicroRail intravascular US catheter (Cardiovascular Imaging Systems, Inc, Sunnyvale, CA) was placed through the core lumen of the manometry catheter in such a fashion that the US transducer was positioned just distal to the tip of the catheter (Figure 1). The latter arrangement allowed us to record pressure and US images from almost the same location (2–3 mm apart) in the esophagus, and it also captured a 360° US image of the esophagus. The US transducer was encased in a water-filled polyethylene bag of the same diameter as the manometry catheter. The catheter assembly was introduced through the nose into the stomach after topical anesthesia of the nasal cavity and oropharynx using 1% lidocaine gel and 1% benzocaine spray. The station pull-through technique was used to determine the location of the lower esophageal sphincter (LES). The recordings were performed at 2 levels in the esophagus: 2 cm and 10 cm above the LES. Five to 6 swallows of 5 mL of water at room temperature were recorded at each of the 2 levels. Swallows were performed 30 seconds apart, and subjects refrained from swallowing in between the swallows. Pressures were recorded on a computer through Polygraph ID and Polygram 98 (Medtronic Synectics, Shoreview, MN). US images were recorded on an S-VHS tape recorder using an HP Sonos 100 machine (Hewlett-Packard, Watertown, MA). The pressure and US recordings were synchronized using a time code device (Thalaner Electronics, Ann Arbor, MI) 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. The time intervals of 10 milliseconds can be resolved in this method of recording. The US images were digitized using a video editing device (Pinnacle Express; Pinnacle Systems Inc, Mountain View, CA) on a personal computer program (Adobe Premiere 6.0; Adobe Systems Inc, Mountain View, CA) and analyzed using a commercially available image analysis software package (Sigma Scan Pro; Jandel Scientific, San Rafael, CA). The US images were quantitated every 250 milliseconds for a period of 10 seconds before and 20–40 seconds after the onset of each esophageal contraction (based on the pressure tracings). Therefore, for each swallow, a total of 120–200 US images were analyzed. The inner and outer borders of the muscularis propria, which includes both the circular and longitudinal muscle layers and the intermuscular septum, were identified visually and marked on the images using a personal computer and image analysis software package. The inner border represented the boundary between the outer margin of the mucosa and the inner margin of the circular muscle layer, and the outer border was the interface between the outer margin of the longitudinal muscle layer and the adventitia of the esophagus. The muscle CSA was calculated from the inner and outer borders of the muscularis propria. The CSA of the inner ring was used to determine the luminal radius (Figure 1). Baseline muscle CSA was measured from the 4 images during the first second of each swallow sequence (4 frames before swallow). Baseline pressure was defined as the end-expiratory pressure before the onset of contraction. The onset of manometric contraction was defined at the point of the rapid upstroke on the pressure wave (rate of pressure increase, >40 mm Hg/s). This point usually follows the bolus pressure wave, which is the initial slow and small increase in pressure corresponding to the pressure values of at least 5 mm Hg greater than the baseline pressure. The end of the pressure wave was defined as the point at which it returned to the baseline value (Figure 2). We determined the precise temporal relationship between US images, muscle CSA, and contraction pressure wave using a plot that included M-mode images of the esophagus, muscle CSA, and pressure wave arranged in a perfectly synchronized fashion. M-mode images were obtained from the 2-dimensional US images using specially designed software developed in our laboratory.7Bhargava V. Jung H.-Y. Bhalla V. Puckett J.L. Liu J. Mittal R.K. Derived M-mode ultrasonography a valuable imaging modality for the visual assessment of esophageal motility (abstr).Gastrointest Endosc. 2004; 59: AB220Abstract Full Text Full Text PDF Google Scholar Analog HFIUS images were digitized off-line frame by frame for the entire duration of the swallow sequence at 30 frames/s (30 Hz). By sectioning 2-dimensional stacked HFIUS images along a line passing through the center of the catheter, identified on the 2-dimensional image, an M-mode image was created. The muscle CSA measured from the B-mode US images and pressure waves obtained digitally were temporally aligned and superimposed on the M-mode US images (Figure 3). The onset of the muscle CSA wave was defined as the point when CSA increases from its minimal value (Figure 2). The end of the muscle CSA wave was defined as the point when it returns to the baseline value. We also determined the onset of lumen collapse from the M-mode US images, defined as a point at which the fully distended esophagus during swallow starts to collapse (ie, reduction of lumen dimension). Complete lumen collapse was defined as the point at which the esophageal lumen all around the circumference of the mucosa of the esophagus collapses on the US probe (Figure 3). The relationship between time interval (δ-t) and (1) peak contraction amplitude, (2) contraction duration, and (3) peak muscle CSA was determined during all swallows in healthy subjects and patients. Central tendencies and range of pressure and muscle CSA are expressed as the median, minimum, and maximum range. The nonparametric test for comparing various parameters between the 2 patient populations was the Wilcoxon test. A Spearman test was used to determine the correlation between the degree of asynchrony between the pressure and muscle CSA. Coefficient of variance was used to determine the variability of the duration of contraction pressure wave and muscle CSA wave. F test was used to determine the differences between intrasubject and intersubject variability. P < .05 was considered significant. Table 1 is a summary of the pressure and muscle CSA data of the 2 groups. The amplitude of peak pressure and peak muscle CSA was significantly greater in the high amplitude esophageal contraction (HAEC) patients at both 2 cm and 10 cm above the LES as compared with healthy subjects. In addition, the baseline muscle CSA was significantly greater in the patients at both levels in the esophagus as compared with healthy subjects.Table 1Comparison of Pressure and Muscle CSA Data Between Healthy Subjects and Patients With Nutcracker EsophagusLevelGroupBaseline CSA (mm2)Peak valueDuration (seconds)Pressure (mm Hg)CSA (mm2)Pressure (mm Hg)CSA (mm2)2 cm5 healthy subjects (28 swallows)53 (37–67)91 (35–178)103 (67–137)3.8 (2.5–6.3)6.5 (5.3–8.5)10 patients (52 swallows)88aP < .05 compared with healthy subjects using Wilcoxon rank sum test. (33–142)217aP < .05 compared with healthy subjects using Wilcoxon rank sum test. (76–701)165aP < .05 compared with healthy subjects using Wilcoxon rank sum test. (80–222)6.0aP < .05 compared with healthy subjects using Wilcoxon rank sum test. (3.0–14.0)7.0 (4.0–16.5)10 cm5 healthy subjects (28 swallows)39 (33–58)113 (64–182)89 (74–123)4.0 (3.0–4.75)6.75 (5.75–7.5)10 patients (51 swallows)53aP < .05 compared with healthy subjects using Wilcoxon rank sum test. (22–104)128aP < .05 compared with healthy subjects using Wilcoxon rank sum test. (56–256)116aP < .05 compared with healthy subjects using Wilcoxon rank sum test. (55–187)4.3 (2.8–7.5)7.0 (4.5–12.0)NOTE. All data are shown as median (range).a P < .05 compared with healthy subjects using Wilcoxon rank sum test. Open table in a new tab NOTE. All data are shown as median (range). We analyzed 28 swallows at the 2-cm site and 28 swallows at the 10-cm site in healthy subjects. At each site, swallows resulted in bolus-induced distention followed by the collapse of the esophageal lumen and esophageal contraction. The increase in muscle CSA was synchronous with the onset of esophageal lumen collapse (Figure 3). The onset of manometric contraction coincided with the first complete collapse of the lumen on the manometric probe, following which muscle thickness and pressure increased simultaneously. The increase in muscle CSA occurred before the onset of pressure wave, but the two peaked simultaneously with a maximum separation between the peaks (δ-t of 0.5 seconds) (Figure 3A). The peak CSA occurred either earlier than or at the same time as the peak pressure but never later than the peak pressure. The temporal relationship between the previously described events was similar at 2 cm and 10 cm above the LES. In the patients with nutcracker esophagus, 52 swallows at 2 cm and 51 swallows at 10 cm above the LES were analyzed. Similar to healthy subjects, swallows resulted in distention of the esophagus followed by lumen collapse. The onset of manometric contraction coincided with the first total collapse of the esophageal lumen on the recording probe (Figure 3B). The onset of increase in muscle CSA preceded the onset of pressure wave by an average of 1.93 seconds, which was significantly greater than in the healthy subjects (1.56 seconds) (Figure 4). The peak muscle CSA and the peak pressure, unlike in healthy subjects, revealed greater temporal asynchrony. Peak muscle CSA occurred before the peak pressure, with δ-t ranging from 0.75 to 3.5 seconds (median δ-t, 1.25 seconds) at 2 cm and from 0 to 2.0 seconds (median, 0.75 seconds) at 10 cm above the LES. While δ-t in the healthy subjects was <0.5 seconds during all contractions (both 2 cm and 10 cm), 95% of the contractions in the patient group revealed a δ-t of >0.5 seconds. In some instances (7 of 52 at the 2-cm level), the muscle CSA returned almost to the baseline value while the contraction pressure was still increasing. δ-t at the 2-cm level was greater than the δ-t at the 10-cm level in the patient group, suggesting a greater asynchrony between the 2 muscle layers in the distal as compared with a relatively proximal site in the esophagus (Figure 4). Contraction amplitude, duration of pressure, and peak muscle CSA were significantly larger at 2 cm compared with 10 cm above the LES in the patient group (for all, P < .001). The δ-t variability during esophageal contractions was less in a given subject as compared with between subjects (F test; P < .05). The rate of pressure increase in the patient group was higher (104 ± 42 mm Hg/s) as compared with healthy subjects (67 ± 29 mmHg/s) (P < .001), which suggests that the longer δ-t in patients is not caused by the slow rate of contraction of the circular muscles of the esophagus. M-mode images revealed the temporal relationship between the changes in muscle thickness and the pressure wave. Similar to muscle CSA, muscle thickness peaked earlier than the peak of pressure wave in patients (Figure 3). A statistically significant correlation was found between δ-t and peak contraction amplitude, contraction duration, and peak muscle CSA, with r values ranging from 0.613 to 0.746 (Figure 5). However, all 13 contractions with normal contraction amplitude (<180 mm Hg, 2-cm level) in the patient group demonstrated a δ-t >0.5 seconds (Figure 6), suggesting that asynchrony can occur in the presence of normal contraction amplitude in patients but not in healthy subjects.Figure 6An example of wide time lag (δ-t) between the peak of muscle CSA and the peak pressure in a patient with nutcracker esophagus with normal amplitude contraction. This swallow sequence showed 1.25-second dissociation and a contraction pressure amplitude of 160 mm Hg. (δt=1.25 sec).View Large Image Figure ViewerDownload (PPT) Figure 7 shows the relationship between the durations of pressure wave and the muscle CSA wave in healthy subjects and patients. In healthy subjects, the duration of pressure wave was shorter than that of the muscle CSA wave at both 2 and 10 cm above the LES. The duration of pressure wave at 2 cm was longer in the patients as compared with healthy subjects; however, unlike in healthy subjects, there was no difference in the duration of pressure and muscle CSA waves in the patients. The latter observation suggests that the duration of the circular but not the longitudinal muscle contraction may increase in the patients. At the 10-cm level, on the other hand, there was no difference in the duration of pressure wave between healthy subjects and patients and, similar to healthy subjects, the duration of muscle CSA was longer than the duration of pressure wave in patients. Our data showed the following. (1) The peak of circular and longitudinal muscle contraction occurred almost synchronously (δ-t <0.5 seconds) in healthy subjects, but patients with nutcracker esophagus showed disassociation between the peak contraction of the 2 muscle layers at the 2-cm and 10-cm sites above the LES. The asynchrony was greater at the 2-cm site as compared with the 10-cm site. (2) There was a significant correlation between the degree of asynchrony of peak contraction of the 2 muscle layers and contraction amplitude, contraction duration, and peak muscle CSA. (3) The duration of the pressure wave (circular muscle contraction) but not the muscle CSA (longitudinal muscle contraction) was increased in patients with nutcracker esophagus. We, for the first time, report asynchrony between the contractions of 2 muscle layers during peristalsis in patients with nutcracker esophagus. Furthermore, the asynchrony was greater at 2 cm as compared with 10 cm above the LES, a finding compatible with the general belief that nutcracker esophagus and other spastic disorders affect the distal esophageal muscle more than the proximal esophageal muscle.8Clouse R.E. Staiano A. Topography of normal and high-amplitude esophageal peristalsis.Am J Physiol. 1993; 265: G1098-G1107PubMed Google Scholar The validity of our observation depends on the accuracy of our recording techniques, specifically with regard to the temporal alignment of acquisition systems for recording pressure and US images. We used a video timer that imprints time on the recorded video images. This clock imprints hour, minute, and second to a one hundredth of a second resolution on the video images. The video timer also sends 1-mV pulses to the polygraph every second. Therefore, the system allows temporal alignment of physiologic signals with US images with an accuracy of one hundredth of a second. US images were recorded on an NTSC videotape recorder (imaging frequency of 29.97 Hz), and therefore the changes in US images can be detected with an accuracy of one thirtieth of a second, or 33.3 milliseconds. M-mode image temporal resolution is the same as the video frame rate (33.3 milliseconds). The M-mode US images superimposed with the muscle CSA and the pressure signal showed that the onset of contraction pressure coincided with the onset of first complete lumen collapse around the recording probe. Because manometry records the onset of contraction wave at the initial contact of the mucosa with the manometry catheter, we believe that our synchronization system is accurate. Based on the frequency of the muscle CSA measurements (4 Hz), the accuracy of δ-t in our studies was 0.5 seconds. We found that the δ-t was never >0.5 seconds in healthy subjects. On the other hand, almost all contractions in the patient group revealed a δ-t >0.5 seconds, and in 2 contractions it exceeded 3 seconds. Another factor that may influence the accuracy of δ-t is related to the displacement between the pressure recording and US imaging recording sites in our experiment. The pressure was recorded 2–3 mm proximal to the image recording site. The reason for doing so was that our recording technique, unlike others in which the pressure and US images are recorded at the same site, allowed us to capture a full 360° view of the esophagus.1Miller L.S. Liu J. Colizzo F.P. Ter H. Marzano J. Barbarevech C. Helwig K. Leung L. Goldberg B.B. Correlation of high-frequency esophageal ultrasonography and manometry in the study of esophageal motility.Gastroenterology. 1995; 109: 832-837Abstract Full Text PDF PubMed Scopus (70) Google Scholar, 2Nicosia M.A. Brasseur J.G. Liu J. Miller L.S. Local longitudinal muscle shortening of the human esophagus from high-frequency ultrasonography.Am J Physiol Gastrointest Liver Physiol. 2001; 281: G1022-G1033PubMed Google Scholar, 3Pehlivanov N. Liu J. Kassab G.S. Puckett J.L. Mittal R.K. Relationship between esophageal muscle thickness and intraluminal pressure an ultrasonographic study.Am J Physiol. 2001; 280: 1093-1098Google Scholar, 5Yamamoto Y. Liu J. Smith T.K. Mittal R.K. Distension related responses in the circular and longitudinal muscles of the esophagus an ultrasonographic study.Am J Physiol Gastrointest Liver Physiol. 1998; 275: G805-G811Google Scholar We do not believe that our conclusions are affected by our recording technique. First, we studied healthy subjects and patients in an identical fashion. Second, we recorded circular muscle contraction at a site proximal to the longitudinal muscle contraction site, yet we found that the CSA peaks either earlier or at the same time as the pressure peak, a finding similar to those made by others who recorded pressure and US images at the same location.1Miller L.S. Liu J. Colizzo F.P. Ter H. Marzano J. Barbarevech C. Helwig K. Leung L. Goldberg B.B. Correlation of high-frequency esophageal ultrasonography and manometry in the study of esophageal motility.Gastroenterology. 1995; 109: 832-837Abstract Full Text PDF PubMed Scopus (70) Google Scholar, 2Nicosia M.A. Brasseur J.G. Liu J. Miller L.S. Local longitudinal muscle shortening of the human esophagus from high-frequency ultrasonography.Am J Physiol Gastrointest Liver Physiol. 2001; 281: G1022-G1033PubMed Google Scholar Another limitation of our data analysis could be that we collected multiple swallows from each subject and made swallows instead of subject the unit of analysis, which creates the potential for bias because the variability within subjects is lower than the variability between subjects. However, the analysis was based on equal numbers of swallows from each subject to minimize biasing the results by overrepresenting atypical subjects. Furthermore, nonparametric statistical tests were used to adjust for the heterogeneity of variance. Several investigators have studied the relationship between the contractions of circular and longitudinal muscles of the esophagus. Sugarbaker et al implanted strain gauzes in the axis of circular and longitudinal muscles of the esophagus in the opossum and came to the conclusion that the longitudinal muscle contracts before and outlasts the circular muscle contraction and that the peak contraction occurs at the same time.9Sugarbaker D.J. Rattan S. Goyal R.K. Mechanical and electrical activity of esophageal smooth muscle during peristalsis.Am J Physiol Gastrointest Liver Physiol. 1984; 246: G145-G150Google Scholar, 10Sugarbaker D.J. Rattan S. Goyal R.K. Swallowing induces sequential activation of esophageal longitudinal smooth muscle.Am J Physiol. 1984; 247: G515-G519PubMed Google Scholar Pouderoux et al11Pouderoux P. Lin S. Kahrilas P.J. Timing, propagation, and effect of esophageal shortening during peristalsis.Gastroenterology. 1997; 112: 1147-1154Abstract Full Text PDF PubMed Scopus (109) Google Scholar used mucosal clips along the length of the esophagus and manometry to study the circular and longitudinal muscles and arrived at the same conclusion as Sugarbaker et al. Miller et al1Miller L.S. Liu J. Colizzo F.P. Ter H. Marzano J. Barbarevech C. Helwig K. Leung L. Goldberg B.B. Correlation of high-frequency esophageal ultrasonography and manometry in the study of esophageal motility.Gastroenterology. 1995; 109: 832-837Abstract Full Text PDF PubMed Scopus (70) Google Scholar and Nicosia et al2Nicosia M.A. Brasseur J.G. Liu J. Miller L.S. Local longitudinal muscle shortening of the human esophagus from high-frequency ultrasonography.Am J Physiol Gastrointest Liver Physiol. 2001; 281: G1022-G1033PubMed Google Scholar used a high-frequency US imaging technique and manometry to study the longitudinal and circular muscle, respectively, and found that the increase in muscle CSA occurs earlier and outlasts the pressure wave, which is consistent with our findings. Furthermore, similar to our findings, they also found that the peak of contraction of the 2 muscle layers occurs almost synchronously in healthy subjects (δ-t, <0.5 seconds). These observations may be interpreted that the longitudinal muscle contraction starts earlier than the circular muscle contraction and the contraction of 2 layers peak together. However, if one considers the onset of lumen collapse, rather than the onset of manometric contraction, as the marker of the onset of circular muscle contraction, then the onset of contraction of 2 layers is synchronous in healthy subjects and patients. On the other hand, if one considers the onset of manometric contraction as the marker for the onset of circular muscle contraction, then the latter is somewhat delayed in relationship to the increase in muscle CSA in patients as compared with healthy subjects. The asynchrony of contraction between the 2 muscle layers during peristalsis is more obvious at the peak of contraction rather than the onset of contraction. It is interesting that the asynchrony between the circular and longitudinal muscle contraction is unique to patients with nutcracker esophagus, but it is not entirely dependent on the amplitude of contraction because even some of the normal-amplitude contractions in these patients demonstrated this phenomenon. The latter may suggest that the asynchrony between the contractions of 2 muscle layers is a manifestation of the pathologic or diseased state. Furthermore, the asynchrony is greater at 2 cm as compared with 10 cm above the LES, a finding compatible with the general belief that nutcracker esophagus and other spastic disorders affect the distal esophageal muscle more than the proximal esophageal muscle.8Clouse R.E. Staiano A. Topography of normal and high-amplitude esophageal peristalsis.Am J Physiol. 1993; 265: G1098-G1107PubMed Google Scholar To our knowledge, the mechanism of coordination between the 2 muscle layers of the esophagus during peristalsis has never been reported. However, it is generally believed that timing and propagation of contraction during peristalsis are related to the neural element. These neural elements could be located at the level of the vagal complex or myenteric plexus. On the other hand, amplitude and duration of contraction are more likely to be related to the properties of the muscles themselves. We believe that, during peristalsis, the true onset of circular muscle contraction is the onset of lumen collapse, which occurs at the same time as the increase in muscle CSA (marker of longitudinal muscle contraction) in healthy subjects and patients with nutcracker esophagus. Therefore, onset of contraction of 2 muscle layers is in synchrony in patients with nutcracker esophagus. The asynchrony of contraction in the time to peak contraction and duration of contraction of 2 muscle layers seen in our study is likely to be related to the muscles themselves. Even though our study does not allow us to conclude the precise mechanisms of asynchrony, our finding of an increase in muscle thickness in patients with nutcracker esophagus may indicate a muscular etiology of asynchrony. What is the clinical significance of asynchrony between the contractions of 2 muscle layers? Contraction of the longitudinal muscle during peristalsis increases the thickness of the muscularis propria and, in accordance with Laplace's law, reduces the wall stress at the site of contraction. Temporal synchrony between the contractions of 2 muscle layers assures that the maximal thickness occurs at the time of maximum pressure, which guarantees a relative homeostasis of the wall stress during the entire period of contraction.12Puckett J.L. Bhalla V. Liu J. Kassab G. Mittal R.K. Esophageal wall stress Potential mechanism of increased muscle thickness in patients with high amplitude esophageal contractions (abstr).Gastroenterology. 2004; 126: A-27Google Scholar, 13Pal A. Brasseur J.G. The mechanical advantage of local longitudinal shortening on peristaltic transport.J Biomech Eng. 2002; 124: 94-100Crossref PubMed Scopus (64) Google Scholar, 14Takeda T. Kassab G. Liu J. Puckett J.L. Mittal R.R. Mittal R.K. A novel ultrasound technique to study the biomechanics of the human esophagus in vivo.Am J Physiol Gastrointest Liver Physiol. 2002; 282: G785-G793PubMed Google Scholar The stress homeostasis has been studied extensively in blood vessels.15Kassab G.S. Gregersen H. Nielsen S.L. Liu X. Tanko L. Falk E. Remodeling of the coronary arteries in supra-valvular aortic stenosis.J Hypertens. 2002; 20: 2429-2437Crossref PubMed Scopus (45) Google Scholar, 16Liu S.Q. Fung Y.C. Relationship between hypertension, hypertrophy, and opening angle of zero-stress state of arteries following aortic constriction.J Biomech Eng. 1989; 111: 325-335Crossref PubMed Scopus (178) Google Scholar, 17Laurent S. Arterial wall hypertrophy and stiffness in essential hypertensive patients.Hypertension. 1995; 26: 335-361Crossref Scopus (176) Google Scholar, 18London G.M. Safar M.E. Arterial wall remodeling and stiffness in hypertension heterogeneous aspects.Clin Exp Pharmacol Physiol. 1996; 23: S1-S5Crossref PubMed Scopus (20) Google Scholar An increase of wall stress in blood vessels leads to the formation of an aneurysm.19Vorp D.A. Raghavan M.L. Webster M.W. Mechanical wall stress in abdominal aortic aneurysm influence of diameter and asymmetry.J Vasc Surg. 1998; 27: 632-639Abstract Full Text Full Text PDF PubMed Scopus (348) Google Scholar Asynchrony between the contractions of the 2 muscle layers of the esophagus results in a situation in which the maximal increase in muscle thickness and maximal increase in pressure occur at 2 different times, resulting in an increase in esophageal wall stress at the site of increase in pressure. Similar to an aneurysm in blood vessels, an increase in esophageal wall stress may predispose to the formation of an esophageal diverticulum. It is interesting that the esophageal diverticuli occur in patients with high-amplitude contractions of the esophagus.20Dodds W.J. Stef J.J. Hogan W.J. Hoke S.E. Stewart E.T. Arndorfer R.C. Radial distribution of esophageal peristaltic pressure in normal subjects and patients with esophageal diverticulum.Gastroenterology. 1975; 69: 584-590PubMed Google Scholar, 21Nehra D. Lord R.V. DeMeester T.R. Theisen J. Peters J.H. Crookes P.R. Bremner C.G. Physiological basis for the treatment of epiphrenic diverticulum.Ann Surg. 2002; 235: 346-354Crossref PubMed Scopus (148) Google Scholar We speculate that the asynchrony between the contractions of 2 muscle layers during peristalsis is a risk factor for the formation of an esophageal diverticulum.
Publication Year: 2005
Publication Date: 2005-05-01
Language: en
Type: article
Indexed In: ['crossref', 'pubmed']
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