Relationship between distension-contraction waveforms during esophageal peristalsis: effect of bolus volume, viscosity, and posture

Abstract

High-resolution esophageal manometry (HRM) in its current form assesses only the contraction phase of peristalsis. Degree of esophageal distension ahead of contraction is a surrogate of relaxation and can be measured from intraluminal esophageal impedance measurements. The characteristics of esophageal contractions, i.e., their amplitude, duration, velocity, and modulating factors, have been well studied. We studied the effect of bolus volume and viscosity and posture on swallow-induced distension and contraction and the temporal relationship between the two. HRM impedance recordings of 50 healthy subjects with no esophageal symptoms were analyzed. Eight to ten swallows of 5 and 10 mL of 0.5 N saline and a viscous bolus were recorded in the supine and Trendelenburg positions. Custom-built computer software generated the distension-contraction plots and numerical data of the amplitudes of distension (cross-sectional area) and contraction, and the temporal relationship between distension and peak contraction. The hallmarks of distension waveforms are that 1) distension peak, similarly to contraction, travels the esophagus in a peristaltic fashion, and the amplitude of distension increases from the proximal-to-distal direction; 2) the amplitude of distension is greater with 10 mL than with 5 mL and greater in Trendelenburg than in supine posture; and 3) bolus viscosity increases the amplitude of distension and alters the temporal relationship between distension and contraction waveforms. We describe the characteristics of esophageal distension during peristalsis and the relationship between distension and contraction in a relatively large cohort of normal subjects. These data can be used to compare differences between normal subjects and patients with various esophageal motility disorders in future studies.

NEW & NOTEWORTHY We studied esophageal distension (surrogate of inhibition) ahead of contraction during peristalsis from intraluminal esophageal impedance measurements. Esophageal distension, similarly to contraction, travels the esophagus in a sequential manner, and the amplitude of esophageal distension increases from proximal to distal direction in the esophagus. Bolus volume, viscosity and posture have significant effects on the amplitude of distension and its temporal relationship with contraction.

INTRODUCTION

Each swallow induces a wave of inhibition followed by contraction along the length of the esophagus. The contraction wave travels the esophagus in a peristaltic/sequential fashion along the length of the esophagus. During the inhibition phase, there is cessation of any ongoing contraction in the skeletal and smooth muscle, if present, and relaxation of the tonic activity of the smooth muscles. The esophageal inhibition is followed by contraction, which propels the bolus toward the stomach. The duration of the inhibition increases from the cranial-to-caudal direction in the esophagus, resulting in a delay of contraction in the distal esophagus, also known as the latency period (6, 13, 25). Initial inhibition followed by contraction is the basis of peristalsis or the “law of intestine”, throughout the gastrointestinal tract, described by Bayless and Starling 120 yr ago (2, 3).

Esophageal manometry measures the contraction phase of peristalsis and has provided several important insights into the characteristics of swallow-induced contraction waveforms in the esophagus: 1) the amplitude and duration of contractions are greater in the distal compared with the proximal esophagus; 2) esophageal contraction waveforms generally have a single peak; and 3) bolus volume (9), bolus viscosity (4, 5), and subject’s posture (24, 27) have significant effects on the amplitude, duration, and velocity of esophageal contractions. However, only limited information is available on the inhibitory phase of peristalsis. Deglutitive inhibition, i.e., a second swallow soon after the first swallow inhibits esophageal contraction related to the first swallow and is currently used to study the inhibitory phase of peristalsis during routine manometry studies (12). Using an ingenious system of balloons mounted on the manometry catheter, Sifrim recorded esophageal relaxation associated with single swallows (21, 22). The main function of the inhibitory phase of peristalsis is to allow passage of a bolus with minimal resistance during peristalsis, which is vital to bolus transport. The degree of distension of the esophagus during peristalsis is a surrogate of inhibition: greater inhibition should result in greater distension. Ultrasound imaging to record luminal cross-sectional area (CSA) reveals that the esophageal distension, similarly to contraction, travels along the length of the esophagus in a sequential manner (1, 27).

High-resolution manometry impedance (HRMZ) recordings are done routinely in clinical practice. The impedance component of the HRMZ allows measurement of the luminal CSA of the esophagus (11, 26, 27). Since the currently used HRMZ catheters measure intraluminal impedance every 2 cm along the length of the esophagus, one can measure esophageal distension at closely spaced intervals. In an earlier paper (27), we described the effects of posture on the transit of a bolus in the esophagus. We have now developed a computer software program that allows visualization and quantification of esophageal distension and contraction in several formats, i.e., waveform, topographical plots, and/or a combination of the two. The goal of our study was to determine the characteristics of distension waveforms in a manner similar to what is known about contraction and the temporal relationship between distension and contraction in a large cohort of normal, healthy subjects under various physiological conditions so that future studies may compare these parameters between normal subjects and patients with various motility disorders.

METHODS

Study population.

Fifty healthy subjects (18 males), mean age 36 yr (range 21–74 yr), with no history of gastrointestinal disease or surgery, were part of this study. None of these subjects had symptoms pertaining to the esophagus. The Human Investigation Committee of the University of California, San Diego, approved the study protocol, and all subjects signed an informed consent form before enrollment in the study.

HRMZ recordings.

All subjects were studied using a catheter assembly that consisted of a HRMZ catheter (4.2 mm diameter; Medtronic Inc.), equipped with 36 pressure transducers (1 cm apart) and 18 impedance electrodes (2 cm apart). Viscous Lidocaine (2% lidocaine hydrochloride topical solution, USP) was administered orally and nasally for local anesthesia, followed by placement of the HRMZ-US catheter assembly through the nose. Eight to ten swallows using 0.5 N were performed in each subject under the following iterations: 1) 5 mL in supine and Trendelenburg positions (n = 10 subjects), 10 mL in supine and Trendelenburg positions (n = 40 subjects), and 3) 10 mL of saline and 10 mL of custom-made viscous solution of conductivity similar to 0.5 N, in supine and Trendelenburg positions (n = 10 subjects). For the supine position, the stretcher was in the perfect horizontal condition (parallel to the ground), and for the Trendelenburg (T) position it was tilted to −15° (head of the subject lower than the feet).

Data analysis.

HRMZ data were exported as text files and imported into MATLAB for further analysis. The esophageal luminal CSAs were calculated using principles described in an earlier study (27). A custom-built software program (D-Plots; Motilityviz, La Jolla, CA.) allows a user to import studies and select individual swallows to carry out the analysis. The regions of interest (ROIs) for each swallow were extracted from the HRMZ data by using an interactive rectangle superimposed on the HRM topograph, starting from the onset of upper esophageal (UES) sphincter relaxation to 2 s after the return of lower esophageal (LES) pressure back to baseline at the end of peristaltic contraction. The selected ROI was located between the lower edge of UES and the upper edge of LES. The selected ROI was divided into four equal segments, and the following parameters were extracted: 1) average peak amplitude of distension and contraction in each of the four segments and 2) time period between the onset of UES relaxation and peak distension (i.e., nadir impedance) (T1) and time difference between T1 and peak contraction pressure (T2) at the most distal location in the esophagus.

Statistical analysis.

Quantitative data are reported as means ± SE. The normality of the distributions was checked by the Shapiro-Wilk test. For across (posture, volume) comparisons, we used a nonparametric Wilcoxon signed rank test for all comparisons, and the Wilcoxon rank sum test in the case of nonpaired data. P < 0.05 was deemed significant.

RESULTS

Effect of bolus volume on the distension contraction waveform during peristalsis in the supine position.

Figures 1 and 2 show the impedance pressure topographical plot and distension-contraction waveforms at 18 different locations in the esophagus (2 cm apart) under four different conditions: 5 and 10 mL boluses of 0.5 N saline in the supine and Trendelenburg positions. The distension amplitude increased from the proximal to the distal locations along the length of the esophagus. Esophageal distension at each location in the esophagus is greater, with 10-mL compared with 5-mL swallows (P < 0.01), overall mean (across all 4 segments) 85 ± 7 mm² for supine 5 mL vs. 122 ± 15 mm² for supine 10 mL. Distension is greater in the Trendelenburg (mean of 138 ± 16 mm²) compared with supine posture in all four subsegments (P < 0.01). Peak esophageal contraction amplitude also increased, with the increase in bolus volume; the effects were significant in segment 2 (P < 0.01) in the supine posture and segment 2 (97 ± 30 mmHg for 5 mL vs. 113 ± 24 mmHg for 10 mL, P < 0.01) and segment 3 (P < 0.05) in the Trendelenburg posture, 133 ± 53 mmHg for 5 mL vs. 156 ± 47 mmHg for 10 mL (Fig. 3).

Fig. 1.

Sample 0.5 N saline swallows in supine and Trendelenburg positions for 5-mL (A and B) and 10-mL (C and D) swallows. Each panel consists of a pressure topograph (right), a combined pressure topograph with isocontour of (20 mmHg) shown in pink, and the corresponding impedance values shown as bars. Note that bar colors turn more red in the Trendelenburg position (high impedance), representing air moving ahead of saline bolus as a result of change in posture. Also note the increase in contraction amplitude in the transition zone going from supine to Trendelenburg position.

Fig. 2.

Distension-contraction (DC) plots of 5-mL (A and B) and 10-mL (C and D) swallows in supine and Trendelenburg positions. Note a shorter T2 time in the Trendelenburg position, and amplitude of distension more in the distal compared with proximal location and from supine to Trendelenburg position. Both pressure and distension share the z-axis limits.

Fig. 3.

Comparison of mean peak distension (A) and peak pressures (B) with 5- and 10-mL saline (S) swallows. Also, comparison of peak distension (C) and peak pressures (D) with 10-mL saline and 10-mL viscous (V) bolus in both supine and Trendelenburg (TB) positions. Numbers of subjects for each comparison are provided in methods.

Effect of posture (supine vs. trendelenburg) on the distension contraction waveform during peristalsis.

Figure 4 shows two swallows, each 10 mL, 0.5 N saline, one in the supine and the other in the Trendelenburg position. These images display the dynamics of bolus movements and the temporal relationship between the distension and contraction of the esophagus along its entire length during a 12-s period immediately following the onset of swallow. In this display, the location and amplitude of distension as well as the location and amplitude of contraction along the whole length of the esophagus are displayed (41 images for each of the 2 swallows, spaced 0.3 s apart, during the 12-s period). Important features of the esophageal distension-contraction waveforms in these figures are that 1) the esophageal contraction is behind (orad) and esophageal distension in front of contraction, the two distinct compartments/domains of the esophagus during peristalsis; 2) the bolus travels the esophagus in the shape of an “American football”, more so in the Trendelenburg than in the supine position; 3) the degree of esophageal distension increases as the bolus travels from the proximal to the distal location; 4) the length of the esophagus that is distended with the bolus is smaller in the Trendelenburg position (compact bolus); and 5) the bolus moves in closer proximity to the contraction in the Trendelenburg position compared with the supine position. Figure 3 shows a summary of the data from all subjects, comparing esophageal distension and contraction in the supine and Trendelenburg positions. Similar to the findings shown with a single swallow in Fig. 4, the mean data in Fig. 3 confirm the above-mentioned findings. The effect of posture on mean contraction amplitude, i.e., greater amplitudes are significant in segments 1 and 2. On the other hand, peak distension amplitude is significantly higher in the Trendelenburg position in the first 3 segments of the esophagus but not in segment 4.

Fig. 4.

Sample swallow comparing supine and Trendelenburg positions. Pressure is shown as a color topograph (jet map color) superimposed on a distended esophagus. Note the increase in intrabolus pressure in Trendelenburg position and the proximity of the peak of distension with contraction waveforms, which indicates the prominence of the pharyngeal pump in bolus propulsion in the supine position compared with the Trendelenburg position.

Effect of posture on the temporal relationship between distension-contraction waveform during peristalsis.

In the supine position, the bolus traveled to segments 3 and 4 of the esophagus relatively quickly after the swallow, but the contraction wave arrived in the distal esophagus much later than the bolus. On the other hand, in the Trendelenburg position, the bolus arrival in the distal esophagus took significantly longer, and the peak of distension traveled in close proximity to the onset and peak of contraction. Consequently, the T1 was longer and T2 shorter in the Trendelenburg position (P < 0.01). The total time for the contraction peak to travel the esophagus, i.e., T1 + T2 was not affected by the bolus volume and subject’s posture (Fig. 5).

Fig. 5.

A: sample 10-mL swallow, showing definitions of T1 and T2; T1 (per channel peak distension times) and T2 (per channel difference of peak pressure minus peak distension times) are shown for the 2 postures using 10-mL saline (S; B) and 10-mL viscous bolus (V; C). dashed line denotes SE limits. TB, Trendelenburg position. Numbers of subjects for each comparison are provided in methods.

Effect of bolus viscosity on the amplitude and temporal relationship between distension contraction during peristalsis.

The viscous bolus in the supine position traveled the esophagus in a manner similar to the saline bolus in the Trendelenburg position, i.e., slowly and in close temporal correlation with the contraction waveform (Fig. 6). Hence T1 in the supine position was longer with the viscous compared with the saline bolus in the supine position (P < 0.01), with overall mean changes of 2.53 ± 0.28 and 1.12 ± 0.27 s for viscous and saline bolus, respectively. The peak distension amplitude in all segments was greater with the viscous bolus (with mean 162 ± 14 mm² for viscous bolus, vs. 127 ± 12 mm² for saline bolus) in the supine position compared with the saline bolus in supine (P < 0.01), but only in segment 2 (near the transition zone) in the Trendelenburg position (154 ± 14 mm² for viscous bolus vs. 120 mm² for saline bolus). Unlike the saline bolus, posture (supine vs. Trendelenburg position) had no effect on the amplitude of distension and contraction distally [segments 3 (P = 0.92) and 4 (P = 0.56)] or the temporal relationship between distension and contraction with the viscous bolus (Figs. 3 and 5).

Fig. 6.

Distension-contraction plots of 10-mL 0.5 N saline and viscous bolus in supine and Trendelenburg positions. CSA, cross-sectional area. Note that the bolus travels closer to the contraction wave in the Trendelenburg position with saline swallows. With viscous bolus, the bolus moves closer to the contraction wave in both supine and Trendelenburg positions.

DISCUSSION

In summary, our data show the following findings. 1) Esophageal distension travels sequentially along the length of the esophagus; the amplitude of distension is greater in the distal esophagus than in the proximal esophagus. 2) The amplitude of distension is greater with 10-mL than with 5-mL bolus swallows and greater in Trendelenburg than in supine posture. 3) The end of distension at each location in the esophagus is followed by the onset of contraction. Trendelenburg posture alters the temporal relations between the peak distension and the peak contraction; the saline bolus moves closer to the contraction in the Trendelenburg position. 4) A viscous bolus increases the amplitude of esophageal distension throughout the length of the esophagus. A viscous bolus in the supine posture behaves likes a saline bolus in the Trendelenburg position; i.e., it moves in close proximity to the contraction wave.

The luminal CSA values calculated by the impedance methodology in the current set of data are in close agreement with the measurements made by intraluminal catheter-based ultrasound images in several studies over many years (1, 11, 20, 23, 26, 27). The CSA measurements in our earlier studies were made by different investigators (first authors of those papers) and in different normal subjects than reported in this study. The peak distension amplitude (CSA) in the distal esophagus with bolus volumes of 5 mL in the supine, 10 mL in the supine, and 10 mL in the Trendelenburg positions were ~128 mm², 178 mm², and 190 mm² respectively, which translate into esophageal diameters of approximately 12.7, 15, and 15.6 mm, respectively. With the viscous bolus, the mean amplitude of distension was 200 mm² (diameter 15.9 mm) in the supine and Trendelenburg positions.

Esophageal distension during peristalsis is a surrogate marker of esophageal inhibition. Our finding that the distension amplitude is greater in the distal esophagus than in the proximal esophagus is consistent with the electrophysiological studies in animals that show greater inhibitory innervation in the distal esophagus compared with proximal esophagus (7). Our observation that the bolus travels the esophagus in the shape of an American football is also consistent with our earlier study where luminal CSA was measured using an ultrasound imaging technique (1). The above-mentioned observation is also consistent with electrophysiological studies in animals that revealed gradients of inhibition along the length of esophagus (8). One must keep in mind, though, that, besides neurally mediated inhibition, passive properties of the esophageal wall, i.e., compliance, outflow obstruction and possibly other factors, are likely to determine the amplitude of distension in a given subject in our studies. However, given that we report only normal, healthy, asymptomatic subjects in this study, abnormalities of esophageal wall compliance are less likely to play dominant role in the amplitude of distension that we report in the current study.

Studies show that patients with diffuse esophageal spasm and spastic motor disorders may have problems with the inhibitory phase of peristalsis, which is difficult to measure during routine clinical manometry (21, 22). Distension measurements derived from impedance recordings provide important information about the inhibitory phase of peristalsis and the viscoelastic properties of the esophagus wall. Distension-contraction plots allow easy visualization of the temporal relationship between distension and contraction at closely spaced intervals. We developed a software program that allows automated calculation of distension from the impedance measurements and displays the distension-contraction plots along the entire length of the esophagus in several different formats. Similarly to contraction, the distension can be displayed as topographical color plots (Fig. 1), waveforms (Figs. 2 and 6), and schematic displays of esophageal distension along the length of the esophagus (Fig. 4). These displays also allow easy visualization and quantitation of the temporal relationship between distension and contraction, which we determined as times T1 and T2. We observed that posture and viscosity of bolus have significant influence on the T1 and T2. The saline bolus moves closer to the contraction waves in the Trendelenburg position, and the viscous bolus in the supine position behaves like the saline bolus in the Trendelenburg position.

Measurements of distension and the temporal relationship between distension and contraction have clinical significance. Studies by Omari and colleagues show that patients with functional dysphagia have higher nadir impedance values, shorter T2 values, and greater bolus pressure during the T1 period (15, 17). They found that the pressure flow dynamics allows one to predict development of dysphagia after Nissen’s fundoplication surgery (14, 16). Based on the principles of electrical conductivity and Ohm’s law, a higher nadir impedance value implies smaller distension and smaller T2 implies that the bolus travels close to the contraction wave in these patients. We (10) found alteration in the bolus flow patterns in patients with achalasia esophagus. In patients with achalasia 3 esophagus, even though the bolus clears completely with the swallow-induced contraction, the amplitude of distension is low and there is delay in the arrival of bolus in the distal esophagus compared with normal subjects (18). Studies by Omari and colleagues and our studies in patients were performed with the subjects in the supine position and using saline bolus swallows. In the current study, we found that in normal subjects swallowing a viscous material in the supine position is similar to swallowing a saline bolus in the Trendelenburg position; i.e., the bolus moves closer to the contraction wave (similar to patients with functional dysphagia in the supine position). The amplitude of distension increases in normal subjects in Trendelenburg compared with supine position. The distension amplitude with a viscous bolus is not affected by posture, and it is greater than with a saline bolus. Similar to Omari and colleagues, we also believe that alteration in the bolus flow pattern during peristalsis may play an important role in the genesis of dysphagia symptoms.

In the supine position, one swallows air that is normally present in the pharynx, along with liquid (saline) (19), the two mix in the esophagus and have a significant effect on the conductivity of the swallowed saline bolus. The conductivity value of the swallowed bolus is an important parameter in the calculation of luminal CSA area from the impedance measurement. In the Trendelenburg position, even though one may swallow air along with saline, due to the effect of gravity (air being lighter than liquid), air and saline get separated and traverse separately, air ahead of liquid (26). The latter makes calculation of the luminal CSA from the impedance values more accurate in the Trendelenburg than in the supine position. Our observation that the distension pattern with a viscous bolus in the supine position is similar to the saline bolus in the Trendelenburg position provides a good rationale to perform routine clinical esophageal motility studies with a viscous bolus, given that there may be some concern with regard to placing a patient in the Trendelenburg position during routine manometry recordings.

We propose that display of the HRMZ data in the distension-contraction format allows easy display of normal and abnormal flow patterns in the esophagus. We provide data in a relatively large number of normal subjects to provide normative values against which one should be able to compare patients with nonobstructive (functional dysphagia) and other esophageal motility disorders. These values of luminal CSA during peristalsis are similar to what we (1, 19, 20, 23) have reported in several papers where the CSA was measured using intraluminal ultrasound imaging. We believe that bolus volumes of 10-mL as opposed to 5-mL swallows, done routinely in clinical practice, are more likely to distinguish normal subjects from dysphagia patients in future studies. We propose that the distension-contraction display should become the standard routine of esophageal motility testing.

GRANTS

This work was supported by National Institute of Diabetes and Digestive and Kidney Diseases Grant R01 DK-109376.

DISCLOSURES

No conflicts of interest, financial or otherwise, are declared by the authors.

AUTHOR CONTRIBUTIONS

R.K.M. conceived and designed research; R.K.M. and M.L.-L. performed experiments; R.K.M., K.M., M.L.-L., and A.Z. analyzed data; R.K.M., K.M., and A.Z. interpreted results of experiments; M.L.-L. and A.Z. prepared figures; R.K.M. and A.Z. drafted manuscript; R.K.M., M.L.-L., and A.Z. edited and revised manuscript; R.K.M., K.M., M.L.-L., and A.Z. approved final version of manuscript.