| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
NEUROREGULATION AND MOTILITY
1Department of Mechanical Engineering, The Pennsylvania State University, University Park, Pennsylvania; 2Department of Gastroenterology, University Hospital, Zürich, Switzerland; and 3Department of Gastroenterology, The Royal Melbourne Hospital, Melbourne, Victoria, Australia
Submitted 20 June 2005 ; accepted in final form 3 November 2005
 |
ABSTRACT |
|---|
 TOP ABSTRACT METHODSRESULTSDISCUSSIONREFERENCES |
|---|
esophagus; pressure trough
35% of the esophageal length (15). Manometrically, it is well established that that pressure amplitude during esophageal bolus transport consistently reaches a minimum in the aortic arch region (6). The transition in muscle physiology has been associated with the manometrically measured reduction in muscle contraction activity in the aortic arch region (6, 8), more recently using space-time isocontour representations of manometric pressure by Clouse and Staiano (2, 3). Kahrilas et al. (9) studied esophageal bolus transport in subjects with normal and abnormal bolus transport using conventional manometry and videofluoroscopy, in which they analyzed one case of successful esophageal transport and three cases of incomplete esophageal emptying. One of the latter three cases included a subject with chronic retention of bolus fluid in the aortic arch region. Subsequently, Li et al. (10) developed a mathematical model based on the laws of mechanics to study the contractile behavior of the esophageal wall during normal and abnormal esophageal transport using the manometry fluoroscopy data of Kahrilas et al. (9). Li et al. (10) showed that the computer simulation of bolus retention in the aortic arch region could only be made consistent with the measured pressure by assuming the existence of two separate contraction waves, one above and one below the transition zone (TZ), separated by >4 cm. Li et al. (10) argued that the upper contraction wave (UCW)/lower contraction wave (LCW) reflected the striated/smooth muscle regions of the esophagus and that bolus retention resulted from poor coordination between the UCW and LCW in the TZ. They further hypothesized the existence of two distinct contraction waves in normal esophageal physiology that are spatially and temporally coordinated across the TZ to effect complete bolus clearance during peristalsis.
We tested here the hypothesis of Li et al. (10): that separate contraction waves above and below the TZ are part of normal esophageal physiology and that these contraction waves are well coordinated to prevent bolus retention in the TZ. We analyzed data from concurrent high-resolution manometry and fluoroscopy in asymptomatic subjects and quantified the trajectories of the bolus tail in relationship to the peristaltic waves surrounding the TZ.
|
METHODS |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONREFERENCES |
|---|
Data collection.
Low-compliance perfused manometry (rise rates > 115 mmHg/s) was used to record pressures with a 21-lumen catheter (4.0 mm outer diameter and 0.4 mm lumen diameter, Dentsleeve; Wayville, Australia). Pressures were measured over 28 cm, with the most proximal seven recording sites (sideholes 1–7) spaced 1.5 cm apart, sideholes 7–19 spaced 1.0 cm apart (total: 12.0 cm), a 6-cm sleeve (port 20), and a gastric recording site 1.0 cm distal to the sleeve. Each sidehole, except for sleeve and gastric sideholes, was identified with a radioopaque tantalum marker. Water was perfused through each of the 21 lumina at 0.08 ml/min total. Manometric data were digitized at 125 Hz and median filtered to an acquisition frequency of 25 Hz using the HAD software system (version 5.2.1, G. Hebbard, The Royal Melbourne Hospital, Melbourne, Victoria, Australia). The manometry catheter was preflushed with CO2 to remove air. Perfusion offsets were removed at the beginning of every study by placing the catheter with continuous perfusion in a water bath. The catheter was inserted through an anesthetized nostril, and a pull- through was performed for accurate placement of the sleeve across the lower esophageal sphincter (LES). After completion of the study, the manometry system was checked for drift and blocked pressure sideholes by remeasuring baseline pressures with the catheter placed in the water bath. No significant drift or blocked sideholes were observed. Fluoroscopic images were digitized in situ in eight-bit grayscale and stored at 4 Hz. All swallows analyzed were with 10-ml boluses of high-viscosity radioopaque barium (Micropaque, Guerbet; Roissy, France; density 
2.2 g/ml; viscosity 50,000 cP). Manometry and fluoroscopy data were carefully synchronized in time (t) using an electrical impulse generated by the fluoroscope.
Analysis of image data. Digital AVI movies were created from the fluoroscopic images using an SGI Indigo 4000 computer (Silicon Graphics; Mountain View, CA), and assessments of bolus transport were based on these digital movies. The pattern shown in Fig. 2 was observed in every swallow without exception. As the bolus tail approached the aortic arch region, it slowed and then suddenly "jumped" a finite spatial distance at time tjump [Fig. 2, time instant 7 (t7) = tjump]. Subsequent to the jump, the bolus tail traveled toward the distal esophagus. We quantified this pattern as follows. First, we followed the bolus tail from the upper esophagus to the time when a well-defined point of luminal closure was no longer visible (t7 in Fig. 2). We called the space-time trajectory of the bolus tail up to this point the UCW. Second, starting well below this point where the bolus tail was again clearly defined, we followed the bolus tail backward in time to the instant when the UCW terminated (t7 in Fig. 2). It was observed that this lower bolus tail trajectory always arrived (backward in time) at a point below the termination of the UCW. We therefore refer the lower bolus tail trajectory as the LCW, with the UCW and LCW spatially separated by a distinct "jump." In Fig. 2, the UCW terminates at UCWe and the LCW initiates at LCWb. Finally, once LCWb was identified, the lower wave was followed backward further in time as an indentation that progressively weakened until it was no longer visible. We call the trajectory of this indentation the "indentation wave" (IW). Going forward in time, the IW becomes the LCW at tjump, when the indentation fully occludes the lumen and becomes a true bolus tail. During this formation process, the bolus fluid between the tail of the UCW and the IW was continuously squeezed until the LCW tail formed (tjump). At this time, the region between UCWe and LCWb was either completely depleted of bolus fluid or some bolus fluid was retained as the LCW tail propagated distally. When any amount of retained bolus fluid was visible, its volume was estimated by approximating the retained bolus segments as ellipsoidal. The volume of catheter was excluded. Figure 2 is further discussed in the RESULTS.
|
Muscle squeeze is a consequence of changes in muscle wall stress, which is directly proportional to the transmural pressure difference. We have found in previous analyses of esophageal wall stress (18, 21) that the space-time changes in transmural pressure difference reflect space-time variations in esophageal wall muscle stress. Furthermore, Nicosia and Brasseur (18) showed that in contracting segments, active tone overwhelms passive wall stress. For these reasons, all intraluminal pressures were referenced to intrathoracic pressure. We argue that the resulting space-time pressure characteristics of the TZ presented in this study reflect, qualitatively, space-time changes in active tone.
Intrathoracic pressure was approximated by averaging pressure along the esophageal body in its resting state before the commencement of any swallowing activity over at least five complete breathing cycles. Care was taken to exclude the high-pressure impression of the aortic arch. All pressure magnitudes presented in this analysis are referenced to this estimated intrathoracic pressure. As the subjects were supine, no correction for hydrostatic pressures was required.
Perfused manometry data were recorded as the temporal variation of intraluminal pressure at fixed catheter recording sites along the esophagus (Fig. 1A). To visualize the evolution of the esophageal contractile activity concurrently in both space and time, pressure data were interpolated in space time and plotted as isocontours, as shown in Fig. 1B. The isocontour representation accentuates the space-time structure of the peristaltic contraction wave (2). In Fig. 1B, high pressures are shown in red and low pressures are shown as blue isocontours. In this study, manometry data were interpolated to create 10 virtual ports/cm at 50 Hz using cubic splines on a staggered grid that approximately followed the space-time pressure wave trajectory.
|
We defined the "center" of the TZ as the space-time point of the minimum Pamp within the trough (point C in Fig. 1, B and C). This nadir pressure amplitude (PTZ) during the TZ period (referenced to intrathoracic pressure) was quantified. The upper and lower margins of the TZ were defined based on the spatial variation in Pamp, as described in Fig. 1, C and D. The TZ length (
XTZ) was defined as the distance between the upper and lower margins, and the temporal separation of the TZ (TTZ) was defined as the time difference (in s) of Pamp at the upper margin and lower margin of the TZ.
In addition to space-time local nadir Pamp, we quantified "TZ strength," defined as the average Pamp (referenced to intrathoracic pressure) from the upper to lower margins of the TZ (the shaded region in Fig. 1C divided by XTZ). As discussed above, intraluminal pressure referenced to intrathoracic pressure reflects muscle tone during the transition from UCW to LCW in the TZ. As discussed below, to completely clear bolus fluid from the TZ during evolution from an UCW to a LCW (shown pictorially in Fig. 2, roughly the TZ period shown in Fig. 1), it is necessary that sufficient tone be generated throughout the TZ during the entire period of transition. TZ strength is a measure of average muscle force (per unit area) available to close the TZ segment during the transition period.
Concurrent analysis of manometry and image data. To quantify pressures along the UCW, LCW, and IW, radiographic images and spatially interpolated pressures were placed adjacent to each other and spatially coordinated at fixed times using an interactive in-house computer-based data-analysis system. The series of images coordinated with pressure are shown in Fig. 3. From such series of coordinated data, various pressures and trajectories were quantified during bolus transport through the TZ. The maximum intraluminal pressure at each time instant was defined as PA in Fig. 3. Note that the spatial maximum in pressure defined in Fig. 3 is not the same as the classical Pamp defined in Fig. 1A. During peristaltic transport, PA reflects the maximum muscle squeeze pressure above the bolus tail; PA must exceed the pressure at the bolus tail if luminal closure is be maintained (1). t1 through t7 in Fig. 3 correspond to the same time instants shown in Fig. 2. A computer-based analysis system was developed within the Matlab software environment (version 6.5, MathWorks; Natick, MA) to align and scale the radiographic images adjacent to spatially interpolated manometric pressure (referenced to average thoracic pressure). The following locations and pressures were quantified as a function of time for the coordinated image/pressure data: 1) the bolus tail (XT, PT); 2) the spatial maximum in pressure above the bolus tail (XA, PA); and 3) the IW (XI, PI). Figure 3 is further discussed in the RESULTS.
|
|
RESULTS |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONREFERENCES |
|---|
XTZ was 5.14 ± 2.09 cm (P = 0.0001) and spanned 19.4% ± 6.8 of LE. TTZ was 2.27 ± 0.67 s (P < 0.0001). The center of the TZ was 7.70 ± 1.53 cm below the peak in UES pressure on average. The upper and lower margins of the TZ were 4.87 ± 1.08 and 10.0 ± 1.08 cm below peak UES pressure, respectively. Average PTZ (the lowest pressure in the TZ) was 32.1 ± 11.9 mmHg above intrathoracic pressure. The strength of the TZ (average Pamp through the TZ) was 46.5 ± 12.4 mmHg. These statistics are summarized in Table 1.
|
Xjump [3.32 ± 1.63 cm on average (P = 0.004, CI95 = 2.0–5.1 cm); Table 1]. Figure 4A shows the average over all space-time trajectories of the UCW, LCW, and IW referenced spatially to the midpoint of the jump and temporally to the time of the jump. The shaded rectangular box shown in Fig. 4A shows the average space-time locations of the upper/lower margins of the manometrically defined TZ (Fig. 1B) and the triangle shows the TZ center, all referenced to the center of the jump. The center of the TZ was located spatially and temporally between the UCW and the IW that initiates the formation of a LCW. The spatial jump from the UCW to the LCW occurred, on average, within the lower latter parts of the TZ, and the LCW initiated at the distal margin of the TZ.
|
Figure 4B shows the average PT following the UCW, LCW, and IW. As in Fig. 4A, the shaded region shows the temporal extent of the TZ referenced to the time of the jump. The pressure along the UCW decreased relatively slowly as the bolus tail approached the TZ (3.3 mmHg/s) and then more rapidly as the UCW moved through the TZ (13 mmHg/s). This rapid decrease in tail pressure from 40 to 18 mmHg above intrathoracic pressure as the UCW passed through the TZ was concurrent with the slowing of the UCW (Fig. 4A) and with a rapid rise in pressure along the IW (21 mmHg/s). Statistically, the IW initiated at the ending pressure of the UCW (P = 0.47) and then increased rapidly to initiate the LCW at pressures comparable to the tail pressure of the UCW in the proximal esophagus. The pressure that initiated the LCW (50 mmHg on average) was significantly higher than the ending pressure of the UCW (18 mmHg, P = 0.037).
Aperistaltic physiology of the TZ.
During peristalsis, the spatial maximum in pressure and its location (PA, XA) are generally associated with a propagating bolus tail (PT, XT), as shown in Fig. 3 for the UCW (t1–t4) and LCW (t7 and t8). Figure 3 also shows a spatial jump in PA (XA) between t4 and t5. These jumps in PA were analyzed similarly to the jumps in the bolus tail, as described in METHODS, but were highly resolved in time because the manometry data were collected at 25 Hz (fluoroscopy at 4 Hz).
Figure 5 shows an isocontour representation of an example swallow; higher pressures are shown in red and lower pressures are shown in blue. The white lines show the space-time trajectories of the UCW, LCW, and IW, and the black lines show the space-time trajectories of the spatial maximum in pressure XA versus t, or XA(t). The most proximal pressure maximum trajectory drives the UCW; the most distal pressure maximum wave drives the LCW. In both cases, XA(t) does not cross tail trajectory XT(t) (i.e., the black lines remain proximal to the white lines). However, it was observed that the upper XA trajectory terminates in a jump and crosses the UCW trajectory. This behavior is atypical of a propagating peristaltic contraction because it implies the abolition of the favorable pressure gradient (PA > PT) that drives bolus fluid at the bolus tail. In effect, as the UCW enters the TZ and slows to a stop, the Pamp that had been driving the UCW and maintaining closure at the bolus tail develops aperistaltic behavior. A new pressure maximum develops that is associated with the forming IW. A second jump in XA(t) occurs as the transitional pressure wave realigns itself to the LCW and reestablishes a peristaltic force that drives the LCW into the distal esophagus.
|
XA in Figs. 2 and 6) associated with the TZ region. Spatial jumps in XA(t) typically occurred with the slowing and termination of the UCW and with the formation of the LCW. For a jump to qualify as being associated with the TZ, we required that at least one end of the jump be within the TZ. With this criterion, the average jump width was XA = 2.11 ± 1.76 cm (Table 1). No correlation was found between XA and Xjump.
|
Muscle physiology surrounding the TZ from the UCW to LCW. The closure forces at the bolus tail are reflected by the pressures between PA and PT. The average temporal variations of PA and PT are shown in Fig. 7A. The dotted line is the pressure maximum averaged after UCWe and before LCWb. Figure 7A indicates that the pressure maximum within the TZ is associated with the formation of the IW that precedes the LCW. On average, both PT and PA decreased as the UCW approached and entered the TZ and increased as the IW and LCW moved away from the TZ.
|
|
DISCUSSION |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONREFERENCES |
|---|
Meyer et al. (16) and Clouse and Staiano (2) quantified the location of the pressure trough as 6 cm from the lower margin of the UES, or at 22% of the LE, on average. Mayrand and Diamant (14) applied the smooth muscle relaxant amyl nitrite to the esophagus in vivo and found that striated muscle peristalsis was confined to the proximal 5–6 cm of the esophagus (19–23% of the esophagus), consistent with the distance to the trough. An early histological study (7) of the esophagus claimed that a full 25–30% of the proximal esophagus is striated and 60% of the distal esophagus is fully smooth, implying a very narrow segment with mixed fibers. Meyer et al. (15), however, found from histological study of cadavers that only the proximal 4–5% of the esophagus was fully striated, the distal 54 - 62% of the esophagus was smooth muscle, and the zone of mixed muscle fibers was 35–40% of the LE. In several manometry studies (2, 16, 20), it has been suggested that the manometric pressure trough is correlated with the histological transition in muscle fiber type. Clouse et al. (4) studied the velocity of propagation during peristalsis and demarcated three regions of sequential contraction within the esophagus, with the region between the first and second contraction waves roughly coinciding with the striated-to-smooth muscle transition region. They further demonstrated the presence of two manometrically distinct contraction waves in a subsequent study (5) using the topographic method of analysis. However, in the absence of concurrent radiology studies describing bolus transport, the neurophysiology of the TZ remains a mystery, and the relationship between bolus transport and esophageal contractile activity is unknown. We analyzed here concurrent high-resolution manometry and digital fluoroscopy data to explore the physiology surrounding the TZ of the upper esophagus with bolus transport. In this study, the TZ is objectively defined from high-resolution manometry as a space-time region defined by the trough in Pamp. The minimum Pamp in the trough is the TZ pressure.
Esophageal peristalsis is classically described as the propagation of a wave of active tone and contraction that passes the length of the esophagus, with the TZ explained as a temporary reduction in muscle tone and peristaltic wave speed that produces a pressure trough surrounding a minimum in Pamp (6). By this description, chronic retention of bolus fluid in the aortic arch region reflects an excessive loss of tone and retrograde leakage of bolus fluid as the peristaltic wave traverses the TZ (9, 13). However, it was discovered by Li et al. (10) via physics-based computer simulation of chronic bolus retention during peristaltic transport in the aortic arch region (9) that for their mathematical model to predict the concurrent manometry and fluoroscopy data, it was necessary to assume the existence of two distinct contraction waves: one that reduced in strength and speed above the segment of retained bolus and another that formed concurrently >4 cm below, pinching off the retained bolus fluid as it developed into a fully occluding lower peristaltic wave. Li et al. (10) hypothesized that separate peristaltic waves above/below the TZ are normal esophageal physiology, with the upper wave reflecting the neurophysiology of the upper striated esophagus and the lower wave reflecting a different neurophysiology associated with the smooth muscle lower esophagus. The TZ, rather than a weakening of a single continuous peristaltic wave, was hypothesized to reflect the transition from the UCW to LCW, so that complete/incomplete bolus transport would result from proper/improper space-time coordination of these two distinct waves.
In our study, concurrent high-resolution manometry and digital fluoroscopy were correlated quantitatively through a special-purpose computer-based image manometry-analysis system. Significantly, the two most robust features observed in the each swallow, without exception, were 1) a manometrically well-defined trough in Pamp (Fig. 1) (the average minimum TZ pressure was 32.1 mmHg above intrathoracic pressure); and 2) a fluoroscopically well-defined transition in the position of the bolus tail from an upper to a lower wave trajectory separated by a jump of 3.32 cm on average (Figs. 2 and 4). Given the robustness of these observations, the center of the jump was chosen as the space-time reference. The result was a clear correlation between location of the jump and the TZ (Fig. 4A). We conclude that the hypothesis of Li et al. (10), the existence of distinct upper and lower peristaltic contraction waves as normal esophageal physiology, is confirmed. The transition from the UCW to LCW takes place within the manometrically defined TZ (Fig. 4A). It follows that the space-time changes in esophageal muscle tone associated with this transition defines the physiology of the TZ, manifested manometrically by the temporal changes in spatial structure of pressure, and fluoroscopically by the space-time deformations of the esophageal lumen. Referencing the histological studies that related the pressure trough to the transition in esophagus muscle type, it is reasonable to propose that the neurophysiology underlying the coordination of distinct contraction waves above and below the TZ is associated with a transition in neurophysiological control from the dominantly striated to dominantly smooth muscle esophagus. We elucidate interesting aspects of this transition in neurophysiology with our detailed analyses of space-time relationships between muscle-induced pressure and luminal deformation.
Particularly interesting is the process by which muscle tone transitions from the UCW to LCW, driving deformation of the lumen and interaction with bolus fluid and consequent passage of fluid through the TZ. As the tail of the UCW approaches the TZ, three basic physiological processes take place, as shown by comparing Figs. 4 with 5. The upper wave slows (Fig. 4A), and simultaneously the level of tone (indicated by relative pressure) decreases rapidly (Fig. 4B). During this process, a localized tonic contraction initiates about 2 cm below the tail of the upper wave on average (Fig. 4A), creating an indentation in the lumen (Fig. 2). The level of tone at the initiation of this IW is about the same as the tone at the termination of the UCW (Fig. 4B). As the tonic contraction increases (Fig. 4B), so does the level of indentation (Fig. 2) until bolus fluid is fully depleted locally and the indentation fully occludes the lumen, at roughly the same tonic level as the tail of the UCW above the TZ (Fig. 4B). The indentation initiates a peristaltic wave of tonic contraction that culminates in a fully occlusive LCW that propagates into the distal smooth muscle esophagus (Fig. 4A).
The physiology surrounding the death of the UCW and initiation of the IW and LCW is elucidated in Figs. 2 and 7, where the TZ appears as a special segment that maintains an overall level of tone while a localized tonic contraction above dissipates and, simultaneously, another localized tonic contraction below initiates. The simultaneous process of tonic death above with tonic birth below appears in Fig. 6 as a "rocking" exchange of tone from the UCW to LCW. As illustrated in Fig. 3, during the time period over which the upper wave is exchanged with the lower wave, a sufficient level of tone must be maintained in between to fully deplete the intermediary segment of bolus fluid. At the instant that depletion is complete, the upper wave ceases to exist, and a new tail is born several centimeters below. It is the time instant at which bolus fluid is fully depleted from the segment between the UCW and LCW within the TZ that we quantified as a jump between upper and lower wave tails. The time period of depletion is the time period of the IW, roughly 1.5 s with complete clearance (Fig. 4A). The "strength" of the muscles in the segment of depletion may be quantified by the average pressure within the pressure trough relative to intrathoracic pressure (46.5 ± 12.4 mmHg) and by TZ pressure (32.1 ± 11.9 mmHg). We hypothesize that chronic bolus retention results from impaired neurophysiology of the TZ, producing chronic combinations of weak segmental pressure, extreme separation between UCW and LCW, and/or insufficient clearance time for depletion of bolus fluid during the transition from the UCW to LCW. Occasional discoordination of upper-to-lower wave transition appears to be a part of normal physiology (6).
We focused above on variations in pressure at the bolus tail, especially as required to maintain closure. However, in normal peristalsis pressure (and tone) increases proximal to the tail, to a peak pressure typically 1–2 cm proximal (1) (see also Fig. 2, t1). During normal peristaltic transport, peak pressure exceeds tail pressure, generally by tens of mmHg. At the same time that a peristaltic wave fails to maintain luminal closure at the bolus tail, peak pressure and tail pressure coincide. Therefore, the difference between peak pressure and tail pressure is a measure of the efficacy of peristalsis and the potential for failure to maintain closure. Figure 7 shows that peak pressure and tail pressure approach each other in the TZ. In fact, the pressure difference drops rapidly as the upper wave enters the TZ and is at a minimum during formation of the LCW (Fig. 7B). Thus, during the transition from the UCW to LCW in the TZ, the potential for failure and bolus retention is much higher than during normal peristalsis. The level of minimum pressure difference, we conjecture, is a measure of propensity for failure; the closer the minimum in pressure difference shown in Fig. 7B is to zero, the greater is the potential for retention of bolus fluid in the TZ. Figure 4A indicates that the normal minimum in pressure difference is 8–10 mmHg.
In summary, we have shown that the existence of two distinct waves about the TZ is normal esophageal physiology with a complex segmental space-time transition in tone that leaves the TZ susceptible to failure and bolus retention. We are led to conjecture that chronic bolus retention in the aortic arch region is indicative of pathology in the neurophysiological transition between a poorly coordinated UCW and LCW.
|
FOOTNOTES |
|---|
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
|
REFERENCES |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONREFERENCES |
|---|
This article has been cited by other articles:
|
|
 |
|
  M R Fox and A J Bredenoord Oesophageal high-resolution manometry: moving from research into clinical practice Gut, March 1, 2008; 57(3): 405 - 423. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
