For aim 1 study, the hypothesis is that a correctly performed Valsalva maneuver in the
presence of an inflated bag (stool) in the rectum initiates the rectal peristaltic reflex
that results in contraction of the rectal smooth muscles cranial to the bag and
relaxation of the rectum and internal anal sphincter caudal to the bag. The Fecobionics
device records rectal pressure as a surrogate of abdominal wall contraction. Changes in
rectal pressure, however, can also be related to the contraction of the rectal smooth
muscles. The proposed studies will record, 1) Abdominal wall EMG, and rectal wall
ultrasound imaging, using high frequency ultrasound catheter probe to distinguish the
contribution of abdominal muscle and rectal muscle contraction, respectively to the
rectal pressure, 2) The investigators will study the effects of atropine to inhibit
rectal smooth muscle contraction) on the Fecobionics expulsion, 3) EMG activity of the
EAS during the Fecobionics device expulsion will allow determination of the role of EAS
in the defecation reflex. For these studies, 3 separate experiments are proposed (15
normal healthy volunteers for each aim) to achieve above goals: 1) Record EAS and
abdominal muscle EMG during the Fecobionics expulsion test: if the increase in
intrarectal pressure is related entirely to the abdominal wall contraction, there will be
a perfect spatiotemporal synchrony (not the amplitude) between the abdominal wall EMG and
intrarectal pressure waveform as recorded by the cranial sensor of the Fecobionics
device. Fecobionics and EMG signals can be recorded using wireless system in the private
setting. 2) The investigators will record ultrasound images of the rectal wall using high
frequency ultrasound catheter probe during Fecobionics balloon test. The investigators
expect to observe an increase in the rectal smooth muscle thickness as a marker of active
smooth muscle contraction during rectal peristalsis induced by the Valsalva maneuver. The
ultrasound transducer will be placed at the location of the cranial sensor to visualize
the ascending contraction of the peristaltic reflex (contraction cranial to the distended
bag). 3) The investigators will perform Fecobionics expulsion test before and after
administration of atropine I.V. 15micrograms/Kg. Only the rectal smooth muscle
contraction-induced induced increases in the intrarectal pressure will be eliminated by
atropine (not the abdominal wall skeletal muscle contraction).
For aim 2, The investigators will study 100 patients who meet Rome IV criteria for
chronic constipation will be studied. Fecobionics recordings, along with US imaging of
the rectal wall, EMG recordings of the abdominal wall and external anal sphincter will be
performed, like the ones described in aim 1. In 15 subjects with CC, who fail to evacuate
Fecobionics bag, The investigators will administer edrophonium (Tensilon) 80 μg/Kg) and
repeat the Fecobionics expulsion test. Edrophonium increases the level of acetylcholine
at the neuromuscular synapse to stimulate cholinergic activity and will be expected to
stimulate rectal peristalsis and restore evacuation in patients with abnormalities of
rectal peristalsis. In another 15 subjects with CC who fail to evacuate Fecobionics bag,
The investigators will administer Bisacodyl (2 capsules, 10 mg, dissolved in 10 ml of
saline) into the lumen of rectum through a tubing attached to the Fecobionics device.
5-10 minutes later the investigators will repeat the Fecobionics expulsion test.
Bisacodyl is a stimulant laxative, used routinely in clinical practice. It works at the
level of the enteric nerves to stimulate colon motility. The investigators will test the
hypothesis that stimulation of rectal peristalsis by Bisacodyl restores the Fecobionics
evacuation in patients with defecatory disorder related to the abnormalities of rectal
peristalsis. Fecobionics, EMG and ultrasound image recordings, similar to what we
described in Aim 1 of the study, will be able to assess all of essential elements of
defecatory reflex. The investigators can assess them in a binary fashion whether absent
or present. Based on the studies in normal individuals, however, we will determine the
quantitative values of these parameters and compare them in patients as to which elements
are in the abnormal range. The analysis will generate data to test the hypothesis that
the following elements are part of the defecatory reflex: 1) Rectal distension by the
stool/distended balloon causing an urge to defecate, 2) Correctly performed Valsalva
maneuver that generates some critical threshold level of intra-abdominal pressure, 3)
Rectal peristalsis that cause contraction above the balloon and relaxation of the
internal anal sphincter and 4) Relaxation of the external anal sphincter and puborectalis
muscle
Aim 3 studies will validate a mathematical model of the anorectal passage of the
Fecobionics device to predict the occurrence/non-occurrence of the event in question. In
order to build a successful model, it is critical to know all the variables or parameters
involved in the occurrence of any event. Defecation/evacuation is basically the motion of
liquid/ solid material from rectum across the anal canal to the outside. The two
important players in the evacuation process are the intrarectal pressure (driving force)
and resistive force. The intrarectal pressure can be generated by abdominal wall
contraction and/or rectal muscle contraction related increases in rectal pressure. On the
other hand, resistive forces for the evacuation are related to the IAS, EAS, puborectalis
muscle and frictional forces. Fecobionics data along with the US imaging data, EMG
recordings of abdominal wall and EAS, for the first time should provide all the players
involved in the defecation process. The investigators will be collecting data from the
normal subjects and patients which can be plugged into a mathematical equation to predict
successful event. However, above would only be possible if all the elements in the
defecation/evacuation process are known. The purpose of the modelling experiment will be
to determine if the assumption of known elements of the process of defecation can predict
it correctly. For example, whether anorectal angle is critical for the continence/
incontinence function has never been addressed and the hope is that using modelling
approach we will be able to determine if the above is correct, which can also be true for
the other variables that we will record.
