Departments of 1 Medicine and 2 Surgery, Northwestern University, The Feinberg School of Medicine, Chicago, Illinois
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ABSTRACT |
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Deglutitive inhibition attenuates ongoing esophageal contractions if swallows are separated by short time intervals. This study aimed to determine whether esophageal shortening, mediated by longitudinal muscle, was similarly affected. Eight healthy subjects with two distal esophageal segments demarcated by mucosal clips and manometric recording sites positioned within those segments underwent concurrent manometry and fluoroscopy. Peristaltic amplitude and change in distal segment lengths were quantified during single swallows, paired swallows separated by progressively prolonged intervals, and a series of rapid repetitive swallows. During grouped swallows, deglutitive inhibition with complete attenuation of both the manometric contraction and segment shortening was evident with short-interval swallows and rapid-sequence swallows. No inhibition of either was evident with long-interval pairs. With intermediate interswallow intervals, the occurrence and degree of deglutitive inhibition between peristaltic amplitude and segment shortening were closely correlated. Deglutitive inhibition affects both the longitudinal and circular muscle layers of the esophageal wall, and the occurrence of inhibition evident in one layer is strongly correlated with the other.
peristalsis; swallowing
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INTRODUCTION |
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DEGLUTITIVE INHIBITION is a fundamental property of primary esophageal peristalsis. The peristaltic activity resultant from a swallow is rapidly and completely inhibited by a second swallow if the interval between swallows is inadequate for the first contraction to traverse the striated muscle (proximal) esophagus. Once the peristaltic contraction associated with the first swallow reaches the distal esophagus, a second swallow cannot totally inhibit the contraction but can abort its distal propagation. Deglutitive inhibition can be directly demonstrated experimentally by creating an artificial high-pressure zone in the distal esophagus by wedging a manometric catheter between the wall of the esophagus and a small intraesophageal balloon (10-12). The resultant artificial high-pressure zone is inhibited with swallowing such that the period of inhibition is inversely proportional to the propagation rate of the peristaltic contraction. If a second swallow follows the first by only a short interval, the associated peristaltic contraction may also be attenuated or incomplete as a result of muscle refractoriness (1, 6, 14). Thus the interaction of a second swallow with an earlier swallow is dependent on the interval between the two swallows and can result in attenuation or complete inhibition of either peristaltic sequence.
Note that all of the experiments described above relate to the contraction amplitude of peristalsis as recorded by esophageal manometry. Because contraction amplitude is mainly a function of esophageal circular muscle contraction, it is reasonable to attribute these observations to deglutitive inhibition of the circular muscle layer of the muscularis propria. However, peristalsis also involves a sequenced contraction of esophageal longitudinal muscle. Esophageal shortening (a consequence of contraction of the longitudinal muscle layer of the muscularis propria) has been studied with several techniques: fluoroscopic observation of radiopaque markers sewn to the esophageal muscle (2), fluoroscopic observation of mucosally attached metal clips (3, 4, 8, 9), or observation of dynamic changes in the thickness of the longitudinal muscle layer during intraluminal high-frequency ultrasonograpy (7, 15). Such studies have demonstrated that both layers of esophageal muscle exhibit a coordinated contraction during peristalsis. However, it has yet to be ascertained as to whether or not deglutitive inhibition affects the esophageal longitudinal muscle contraction (esophageal shortening) in the same way that it affects the circular muscle contraction. Thus the aim of this study was to determine whether or not deglutitive inhibition also affects the esophageal longitudinal muscle and, if so, how this correlates with inhibition of the circular muscle.
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METHODS |
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Eight healthy volunteers (3 males, 5 females) free of gastrointestinal symptoms and without a history of upper gastrointestinal surgery were studied. The mean age of participants was 26 ± 1 yr. The study protocol was approved by the Northwestern University Institutional Review Board and informed consent was obtained from each subject. No subjects were taking any medications that could affect esophageal motility. Tobacco use was not permitted on the day of the study.
Endoscopic marking of the esophageal segments by mucosal
clipping.
Subjects fasted overnight before undergoing an esophagoscopy under
sedation with 1-3 mg of intravenous midazolam. During this procedure, three 11-mm stainless steel clips were attached to the
esophageal mucosa using an endoscopic clip-fixing device (HX-3L, Olympus America, Lake Success, NY). Clip 1 was fixed at the
squamocolumnar junction (SCJ), and clips 2 and 3 were placed ~3 and 6 cm proximal, respectively. Clips 1 and 2 thus delineated the distal esophageal segment, whereas
clips 2 and 3 delineated the proximal esophageal segment in the subsequent analysis (Fig.
1). After completion of the clipping
procedure, subjects were allowed to recover from sedation for at least
1 h before proceeding with the remainder of the experimental
protocol. The esophagus was again imaged fluoroscopically 1 mo after
the completion of the study, and mucosal clips that had not
spontaneously dislodged were removed endoscopically.
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Manometric and fluoroscopic evaluation. Manometric recording was performed with a 9-lumen silicone catheter, 3.5-mm outer diameter (Dentsleeve, Bowden, South Australia). A 6-cm sleeve was used to monitor the esophagogastric junction pressures. Side-hole recording sites were spaced 3 cm apart proximal to the sleeve center, with an additional site 27 cm above the sleeve center that was used as a swallow marker and another 4 cm distal to the sleeve center used to monitor intragastric pressure (Fig. 1). Manometric recording channels were connected to external pressure transducers that were, in turn, connected to a 16-channel computerized polygraph (Neomedix Systems, Warriewood, New South Wales, Australia) set at a sampling frequency of 40 Hz. The manometric assembly was passed transnasally, positioned such that the sleeve sensor straddled the lower esophageal sphincter, and taped securely to the subject's nose. Subjects laid in a supine posture and were allowed to adapt to the recording apparatus for at least 15 min before experimentation. This was followed by a 15-min baseline recording period. Manometric data were processed using Gastromac software (Version 3.5, Neomedix).
The subject was then positioned under a fluoroscope centered on the lower chest and upper abdomen. Two swallows of 5 ml room-temperature water were imaged fluoroscopically. Thereafter, six to eight paired swallows separated by short, intermediate, or long intervals were tested. The intended separations between the short-, intermediate-, and long-interval paired swallows were 3, 6, and 9 s, respectively. Finally, a series of 10-14 rapid repetitive swallows was done with the subject swallowing as rapidly as possible. Each element of the swallow protocol was separated by at least 30 s. Fluoroscopic images were recorded with a videotape recorder (VO 9800 model; Sony, Tokyo, Japan) at 30 frames/s while the signals detailed in the preceding paragraph were displayed and stored concurrently on the polygraph. Video images and tracings recorded on the polygraph were synchronized using a video timer (model VC 436; Thalner Electronics Laboratories, Ann Arbor, MI) that encoded time in hundredths of a second on each video frame and sent a 1-V, 10-ms pulse to an instrumentation channel of the polygraph at whole second intervals.Data analysis. Fluoroscopic images were analyzed to determine the time course and extent of clip movement. Images recorded during swallow protocols were digitized at 0.5-s intervals and analyzed using image-analysis software to correct for fluoroscopic magnification and to track the movement of each clip. The lengths of the two esophageal segments between the three clips were calculated on each digitized image. Segment lengths were normalized among individuals by establishing the baseline separation as 100% and expressing the separation at subsequent times as a percentage of that value. Maximal shortening of each segment was determined. A shortening index was then calculated to normalize data among subjects. The shortening index was equal to the fractional value of a test swallow over the mean shortening observed with single swallows. For example, if a subject exhibited two single swallows with segmental shortening of 25 and 29% and a paired swallow with shortening of 27%, the shortening index of the paired swallow was {27%/[(25% + 29%)/2]} = 1.
The amplitude of the peristaltic contraction corresponding to segment shortening during swallows was measured from the side-hole recording sites positioned within the limits of each esophageal segment. The mean amplitude was calculated for single swallows for each subject from within each esophageal segment. A contraction index was then calculated to normalize data among subjects. The contraction index was equal to the fractional value of a test swallow over the mean peristaltic amplitude of single swallows. This contraction index was used to correlate contractile amplitude with the percentage of shortening or shortening index. Data were summarized as means ± SE unless otherwise specified. Averaged data were compared using Student's t-test. The Pearson test was used to correlate the percentage of shortening with the contraction index; P < 0.05 was considered significant throughout. ![]() |
RESULTS |
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All subjects completed the protocol without unforeseen problems; clip attachment was easily accomplished, and the procedures were well tolerated. The clips and sites of mucosal attachment were readily identified fluoroscopically.
The intervals between two swallows measured from the pharyngeal recording site on the manometric tracing were 3.2 ± 0.2, 6.2 ± 0.3, and 9.3 ± 0.3 s for short-, intermediate-, and long-interval pairs, respectively. The interval between the first and second swallows during swallowing at maximal rate was 1.4 ± 0.1 s, and the number of swallows was 12 ± 2.
Interactions between swallows. Normally propagated peristalsis was observed in all subjects during the single swallow. In synchrony with the propagated contraction, the two esophageal segments exhibited an immediate initial lengthening (6-9% of baseline length) and subsequent shortening. The segments began to shorten 1-2 s before the arrival of the contractile wave within each segment. Maximal shortening ranged from 15 to 25%. After segment shortening, they regained their initial length before the termination of the propagated contraction within that segment.
With paired swallows, complex interactions were observed between the swallows. Figures 2 and 3 illustrate examples of manometric tracing and esophageal segment shortening from two of the subjects selected because of the clarity with which one exhibited deglutitive inhibition (Fig. 2) and the other exhibited muscle refractoriness (Fig. 3). Note that in both cases during the multiple swallow sequence, only the final swallow was associated with a propagated contractile sequence and an accompanying sequence of esophageal shortening. In Fig. 2, four paired swallows with different intervals are illustrated. When the interval between two swallows was very short (1.9 s), the first swallow was totally inhibited and the second was completely propagated, similar to a single swallow as evident by the manometrically recorded contraction and the sequenced esophageal shortening of both segments. When the interval between swallows was long (8.9 s), each resulted in a completely propagated manometrically recorded contraction and sequenced shortening, although the peristaltic amplitude was slightly lower than that of a single swallow. With paired swallows with intermediate intervals (4.3 and 4.6 s), the first contractile sequence was partially inhibited, evidenced by lower contraction amplitude and early termination of the manometrically recorded contraction in the distal segment. Analogous to this, only the proximal, not distal, segment exhibited slight shortening. On the other hand, the second swallow of the pairs appeared relatively normal, both manometrically and in terms of sequenced shortening.
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Duration of deglutitive inhibition.
Figure 4 summarizes the contraction
amplitudes and the associated percentages of shortening observed during
all single swallows; paired swallows of short, intermediate, and long
intervals; and rapidly sequenced swallows for all subjects. The
contraction amplitude and the extent of shortening observed for a
single swallow, the second swallow of a pair, or the last of a series
of multiple swallows was very similar within both esophageal segments.
However, both peristaltic amplitude and the extent of segmental
shortening were strongly influenced by the duration of the time
interval between the paired swallows. With short intervals, there was
nearly complete inhibition of the first peristaltic contraction both in
terms of peristaltic amplitude and segmental shortening. Conversely, with long-interval swallows, there was no significant inhibition of
peristaltic amplitude or segmental shortening within either esophageal
segment. However, for paired swallows separated by intermediate time
intervals, both segments exhibited significantly lower amplitude and a
reduced extent of shortening (limited to the distal segment). Note that
because deglutitive inhibition was by far the dominant pattern of
interaction observed, the influence of muscle refractoriness is not
evident in Fig. 4.
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Correlation between manometric amplitude and the extent of segment
shortening.
A case-by-case correlation of the contraction index with the shortening
index for the first swallow of every pair is illustrated in Fig.
7. In every instance, the occurrence of a
manometric contraction was accompanied by some degree of segment
shortening. Quantitatively, a highly significant correlation was found
between the contraction index and the percentage of shortening during
the first of the paired swallows (r = 0.6, P 0.001 for the proximal segment, r = 0.66, P
0.001 for the distal segment).
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DISCUSSION |
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The major aims of this study were to determine whether or not deglutitive inhibition affected the longitudinal muscle of the esophageal muscularis propria in a similar manner to the circular muscle and, if so, to determine how the two correlated. Experiments were done using concurrent manometry and fluoroscopy after having demarcated two distal esophageal segments by placement of mucosal clips and situating side-hole recording sites within each segment. The major findings of the investigation were that longitudinal muscle does exhibit deglutitive inhibition, that the degree of attenuation of segment shortening observed strongly correlated with the degree of attenuation of peristaltic amplitude, and that the period of inhibition of segment shortening was 1-2 s less than the inhibition of contractile amplitude within that segment.
The manometric contractions associated with two closely spaced swallows observed in the current study closely parallel the earlier description of Vanek and Diamant (14): with short interswallow intervals (<4 s) or a rapid sequence of swallows, only the final swallow was associated with a propagated contraction; with interswallow intervals >8 s, there were two normal-appearing propagated contractions; with interswallow intervals between 4 and 8 s, there was either significant or complete inhibition of the first propagated contraction. We also observed that in every case, complete inhibition of the manometric contraction was matched by inhibition of shortening in the corresponding segment, and in cases of partial inhibition, the degree of inhibition evident manometrically was closely correlated with the degree to which segment shortening was attenuated. These observations suggest that the property of deglutitive inhibition affects both the longitudinal and circular muscle contractile patterns that are integral to esophageal peristalsis and that if one component is subject to partial or complete deglutitive inhibition, the other is similarly affected.
An elegant investigation by Sifrim et al. (11) used an artificial high-pressure zone in the distal esophagus to demonstrate that normal peristalsis was comprised of a wave of inhibition followed by a sequenced contraction. That investigation uniquely focused on manometric recordings, presumably indicative of circular muscle contractility. In the current study, we tested the hypothesis that deglutitive inhibition is another manifestation of the initial wave of inhibition that precedes the sequenced esophageal contraction. We reasoned that if this were the case, the latency between swallowing and manometrically recorded contraction at a given esophageal locus would closely parallel the period of deglutitive inhibition operational at that locus. As evident by the analysis illustrated in Fig. 5, this relationship is highly significant; deglutitive inhibition persisted in both the proximal and distal esophagus for time periods equal to the respective latencies observed during normal peristalsis. We then tested the hypothesis that deglutitive inhibition of segment shortening, indicative of longitudinal muscle activity, should exhibit similar temporal characteristics. Figure 6 illustrates the findings from that analysis. Note that although there is a clear relationship between the degree of inhibition of shortening and the time reference, inhibition does not persist to time 0 as was the case with the manometric (circular muscle) contraction. In the case of shortening, deglutitive inhibition ends 1-2 s before the time references that were equal to the respective latencies of circular muscle contraction observed during peristalsis. In fact, owing to an inherent methodological limitation of our study, we probably somewhat underestimated the magnitude of the delay between the end of longitudinal and circular muscle inhibition. The methodological limitation in question is that segmental shortening was measured along a 3-cm segment of esophagus, whereas circular muscle contraction was measured at the proximal margin of that segment. Thus, if circular and longitudinal muscle contractions were simultaneous, the inherent error in our measurement would make it appear that the circular muscle contraction preceded the longitudinal muscle contraction, which is the opposite of what was observed. Intraluminal high-frequency ultrasound would overcome this limitation because it can quantify muscle thickness and hence contraction of both layers of esophageal muscle at a given location (7, 15). However, our observation is consistent with earlier observations relating to the relative timing of contraction of the longitudinal and circular muscle during peristalsis. Analysis using methods similar to the current investigation (4, 8, 9), external markers placed directly on the muscularis propria (2), or intraluminal high-frequency ultrasound (7) have all concluded that the onset of longitudinal muscle contraction precedes that of circular muscle contraction.
Swallow-evoked peristaltic sequences are mediated via vagal efferent nerves. Neurophysiological studies in animals support the hypothesis that peristalsis is comprised of active inhibition followed by a sequenced esophageal contraction and that both esophageal inhibition and contraction are centrally mediated (14). Vagal efferent fiber recordings have demonstrated populations of short- and long-latency neurons whose activity temporally corresponds with inhibition and contraction, respectively. Furthermore, the long-latency neurons to the striated and smooth muscles are sequentially activated. Peripheral mechanisms can also mediate sequential esophageal contractions as evidenced by the persistence of secondary peristalsis after thoracic vagotomy (5). No direct neurophysiological data exist regarding the mechanism of deglutitive inhibition of esophageal longitudinal muscle. However, on the basis of the similarities of deglutitive inhibition of the propagated contraction and segment shortening observed in the current investigation, we suspect that the mechanisms are similar, and both likely involve centrally mediated vagal inhibition. Furthermore, centrally mediated vagal inhibition may be the only mechanism operational for longitudinal muscle, because the peripheral mechanism of sequential contraction was not demonstrated in longitudinal muscle (13).
In conclusion, esophageal shortening is affected by deglutitive inhibition in a similar manner to manometrically recorded esophageal contractions. The presence and degree of inhibition evident in peristaltic amplitude closely correlates with those observed in segmental shortening, indicative of longitudinal muscle activity. The deglutitive inhibition evident in both muscle layers is likely attributable to the same vagally mediated inhibition that is an integral component of normal peristalsis, with the caveat that just as the onset of longitudinal muscle contraction precedes circular muscle contraction, the period of deglutitive inhibition of the longitudinal muscle is 1-2 s shorter than that of circular muscle.
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ACKNOWLEDGEMENTS |
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This work was supported by National Institute of Diabetes and Digestive and Kidney Diseases Grant RO1-DK-56033 (to P. J. Kahrilas and R. J. Joehl).
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FOOTNOTES |
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Address for reprint requests and other correspondence: P. J. Kahrilas, Northwestern Univ., Feinberg School of Medicine, Dept. of Medicine, Div. of Gastroenterology and Hepatology, 676 St. Claire St., Suite 1400, Chicago, IL 60611 (E-mail: p-kahrilas{at}northwestern.edu).
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.
10.1152/ajpgi.00311.2002
Received 29 July 2002; accepted in final form 2 December 2002.
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