Characterization of Simultaneous Pressure Waves as Biomarkers for Colonic Motility Assessed by High-Resolution Colonic Manometry

Abstract

Simultaneous pressure waves (SPWs) in manometry recordings of the human colon have been associated with gas expulsion. Our hypothesis was that the SPW might be a critical component of most colonic motor functions, and hence might act as a biomarker for healthy colon motility. To that end, we performed high-resolution colonic manometry (HRCM), for the first time using an 84-sensor (1 cm spaced) water-perfused catheter, in 17 healthy volunteers. Intraluminal pressure patterns were recorded during baseline, proximal and rectal balloon distention, after a meal and following proximal and rectal luminal bisacodyl administration. Quantification was performed using software, based on Image J, developed during this study. Gas expulsion was always associated with SPWs, furthermore, SPWs were associated with water or balloon expulsion. SPWs were prominently emerging at the termination of proximal high amplitude propagating pressure waves (HAPWs); we termed this motor pattern HAPW-SPWs; hence, SPWs were often not a pan-colonic event. SPWs and HAPW-SPWs were observed at baseline with SPW amplitudes of 12.0 ± 8.5 mmHg and 20.2 ± 7.2 mmHg respectively. The SPW occurrence and amplitude significantly increased in response to meal, balloon distention and luminal bisacodyl, associated with 50.3% anal sphincter relaxation at baseline, which significantly increased to 59.0% after a meal, and 69.1% after bisacodyl. Often, full relaxation was achieved. The SPWs associated with gas expulsion had a significantly higher amplitude compared to SPWs without gas expulsion. SPWs could be seen to consist of clusters of high frequency pressure waves, likely associated with a cluster of fast propagating, circular muscle contractions. SPWs were occasionally observed in a highly rhythmic pattern at 1.8 ± 1.2 cycles/min. Unlike HAPWs, the SPWs did not obliterate haustral boundaries thereby explaining how gas can be expelled while solid content can remain restrained by the haustral boundaries. In conclusion, the SPW may become a biomarker for normal gas transit, the gastrocolonic reflex and extrinsic neural reflexes. The SPW assessment reveals coordination of activities in the colon, rectum and anal sphincters. SPWs may become of diagnostic value in patients with colonic dysmotility.

Keywords: anal sphincter pressure; bisacodyl; colonic motility; gastro-colonic reflex; high-amplitude propagating pressure wave; high-resolution manometry; simultaneous pressure waves.

FIGURE 1

A HAPW that develops into a SPW in response to proximal balloon distention, the HAPW-SPW. In this and all other figure panels, the position of a balloon is indicated by a white line. This means that there are 10 cm gaps in this recording at the two white lines. Hence a recording including 80 sensors will have a total reach of 100 cm. In (A,B), the dashes at the right side of the figure represent the position of the sensors (80 sensors were in the colon, spaced 1 cm apart). The proximal colon is at the top of the figures. In (C,D) on the distance axis, 0 is the location of the most proximal sensor. (A) The time period of proximal balloon distention by 240 ml air is indicated by the black line above (A). The balloon is positioned at the proximal white line. Proximal HAPWs developed into SPWs (generating HAPW-SPWs) associated with extensive anal sphincter relaxation. Extensive haustral activity (see Chen et al., 2017; Quan et al., 2017) is seen between 30 and 35 cm following each HAPW. (B) Same as (A), shown are the actual pressure traces. (C) Section of (A) between the first two vertical dashed lines show two HAPW-SPWs that are followed by anal sphincter relaxation. Note that the HAPW evoked by the balloon starts at the most proximal sensor or more proximal. (D) Section of (A) between the 3rd and 4th vertical dashed lines. A low amplitude SPW with anal sphincter relaxation is seen at 1.8 cm. This is followed by an HAPW-SPW and anal sphincter relaxation; the relaxation is preceded by a brief voluntary external anal sphincter contraction. The subject was asked a minute after the motor pattern occurred whether or not the sphincter was voluntarily squeezed. The first HAPW-SPW during balloon distention was associated with bloating, the second with a feeling of urgency. The HAPW-SPW that occurred ∼5 min after balloon distention was associated with urgency. The SPW was not associated with gas or liquid expulsion.

FIGURE 2

Two proximal High Amplitude Pressure Waves (HAPWs) that develop into SPWs: HAPW-SPWs in response to a meal. (A) HAPWs that turn into SPWs with full anal sphincter relaxation. The image shows activity in 100 cm of the colon (position of 84 sensors are shown at the left side of the figure). The activity was observed 12 min after meal intake. The first HAPW-SPW was associated with liquid outflow, the second with liquid and gas expulsion. (B) 3D representation of (A).

FIGURE 3

Amplitude and duration distribution of SPWs and their relationship to gas or liquid expulsion. (A,B) Number of occurrences of SPWs, binned according to amplitudes (A) or duration (B), observed in 17 subjects, before and after a meal and in response to bisacodyl. (C,D) Number of occurrences of SPW amplitudes (C) and durations (D) for SPWs associated with gas or liquid expulsion under all conditions.

FIGURE 4

A proximal HAPW and an HAPW-SPW in response to a meal. (A) Two very similar proximal HAPWs appeared in response to a meal, but only one developed into an SPW. The SPW was accompanied by external sphincter contraction and by sphincter relaxation and gas expulsion. The SPW started at the end of the HAPW, hence it was not pan-colonic. The first HAPW was not asssociated with gas expulsion. Position of the pressure sensors is shown on the left side. (B) 3D rendering of (A). The 0 cm position is in the proximal colon.

FIGURE 5

Rhythmic activity of the internal anal sphincter. (A) Rhythmic activity of the internal anal sphincter at 0.7 cpm. In addition, a short proximal HAPW appears followed by an SPW and full anal sphincter relaxation. This activity was recorded 80 min after meal intake. (B) Low amplitude colonic activity during baseline with rhythmic anal sphincter activity at 1.2 cycles per min.

FIGURE 6

Relaxation of the anal sphincters associated with different motor patterns and in different conditions. Shown is the relaxation of the anal sphincter as a percentage of the anal sphincter pressure just prior to the motor patterns indicated on the X axis. ^∗P < 0.05; ^∗∗∗P < 0.01; ^∗∗∗∗P < 0.001.

FIGURE 7

An HAPW that was not followed by an SPW, was not associated with anal sphincter relaxation. Most HAPWs that are associated with anal sphincter relaxation terminate into an SPW that enters the anal canal. In this subject, an HAPW that terminated suddenly and was not followed by an SPW and did not evoke anal sphincter relaxation. This motor pattern occurred 4 min into a proximal balloon distention (240 ml air). The motor pattern started distal to the balloon distention.

FIGURE 8

Simultaneous Pressure Waves in response to a meal. (A) SPWs that span the entire colon (102 cm). The lighter area, between ∼4 and 12 min, is the time period where the subject sits up causing an increase in intraluminal pressure, and takes in the meal. In this subject, a meal did not induce HAPWs but relatively high amplitude SPWs associated with liquid expulsion. An SPW appeared just before (anticipating the meal) and two following the meal. Anal sphincter relaxations were part of the SPW activity and the SPWs were consistently preceded by relatively low amplitude proximal propagating pressure waves. In addition, a lot of segmenting activity occurred. No pressure waves appeared in the time period between the end of balloon distention and the start of meal intake which was 20 min, except for the one just 1 min before meal intake. All three SPWs were associated with liquid outflow. (B) A 3D rendition of (A). (C) 3D image of an SPW.

FIGURE 9

Rhythmic SPWs after meal intake. (A) Note that SPWs start at sensor 11, hence not in the proximal colon. The SPWs did not obliterate ongoing haustral boundary activities. In vivo, this likely means that under such conditions, gas can pass but stool flow will be restricted by the haustral boundaries. A functional sphincter is prominent, 12 cm above the anal sphincters. The response was observed 44 min after meal intake. There was no gas or liquid outflow. (B) Rhythmic SPWs with anal sphincter relaxation. Note that increasing SPW amplitudes are associated with increasing anal sphincter relaxations. This response was observed 150 min after meal intake. There was gas expulsion with the SPW at 3.5 min, and liquid outflow with the SPWs at 5.5 and 7.4 min.

FIGURE 10

SPWs consist of multiple high frequency pressure waves. (A) Two SPWs appear in response to the meal. They can be seen as consisting of clusters of high frequency multiple pressure waves, suggesting that they may be caused by a cluster of rapidly propagating circular muscle contractions as was shown to be the case in the rabbit colon (Quan et al., 2017). (B) 3D image of (A).

FIGURE 11

A high amplitude SPW associated with balloon expulsion. (A) Two SPWs appear in response to rectal balloon distention; the dark area above the anal sphincter shows the pressure in the rectum induced by the balloon. The first SPW was associated with liquid outflow. The second SPW consists of a cluster of high frequency multiple pressure waves, the last wave at 55 mmHg is followed by relaxation of the sphincter and it expels the balloon. Preceding the balloon expulsion, the SPW was associated with pain and urge. (B) 3D image of (C), the balloon distention and anal sphincter activity was removed to make the SPW better visible. (C) Close up of the second SPW as shown in (B) where its composition of multiple pressure waves is clearly visible.

FIGURE 12

High amplitude SPWs in response to rectal bisacodyl. A 10 mg bisacodyl suspension was injected in the rectum at 16 min. Between 3 and 4 min, data acquisition was halted due to refilling of water reservoirs. This subject produced normal HAPWs in response to balloon distention (not shown). The average amplitude of the SPWs in response to bisacodyl was 32.2 mmHg. All 4 SPWs were associated with liquid outflow and the middle two SPWs with gas expulsion as well.

FIGURE 13

Independent HAPWs and SPWs show addition of pressure. (A) Concomittant occurrence of HAPWs and SPWs. The anal sphincter pressure is not shown. (B) A closeup of one of the HAPWs with unrelated SPWs. (C) The 3D graph of (A) shows that the pressures of the HAPW and the SPWs add up. This activity started 8 min after injecting 20 mg bisacodyl suspension in the descending colon. There was no outflow felt.