TY - JOUR
T1 - A pharmacological challenge predicts reversible rectal sensorimotor dysfunctions in women with fecal incontinence
AU - Sharma, M.
AU - Feuerhak, K.
AU - Zinsmeister, A. R.
AU - Bharucha, A. E.
N1 - Funding Information:
The project described was supported by USPHS NIH Grant R01 DKDK78924 and Grant Number 1 UL1 RR024150* from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and the NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH. Information on NCRR is available at http://www.ncrr.nih.gov/. Information on Reengineering the Clinical Research Enterprise can be obtained from http://nihroadmap.nih.gov. ClinicalTrials.gov, No. NCT00884832.
Funding Information:
This study was funded in part by National Institutes of Health grant number RO1 DK 78924 to Dr. Bharucha.
Publisher Copyright:
© 2018 John Wiley & Sons Ltd
PY - 2018/10
Y1 - 2018/10
N2 - Background: In order to understand the pathophysiology of rectal sensorimotor dysfunctions in women with fecal incontinence (FI) and rectal urgency, we evaluated the effects of a muscarinic antagonist and an adrenergic α2 agonist on these parameters. Methods: Firstly, rectal distensibility and sensation were evaluated with a barostat and sinusoidal oscillation at baseline and after randomization to intravenous saline or atropine in 16 healthy controls and 44 FI patients. Thereafter, FI patients were randomized to placebo or clonidine for 4 wk; rectal compliance and sensation were revaluated thereafter. The effect of atropine and clonidine on rectal functions and the relationship between them were evaluated. Results: At baseline, compared to controls, rectal capacity was lower (P =.03) while the mean pressure (P =.02) and elastance (P =.01) during sinusoidal oscillation were greater, signifying reduced distensibility, in FI. Compared to placebo, atropine increased (P ≤.02) the heart rate in controls and FI and reduced (P =.03) the variability in rectal pressures during sinusoidal oscillation in controls. Clonidine increased rectal compliance (P =.04) and reduced rectal capacity (P =.03) in FI. The effects of atropine and clonidine on compliance (r =.44, P =.003), capacity (r =.34, P =.02), pressures during sinusoidal oscillation (r =.3, P =.057), pressure (r =.6, P <.0001), and volume sensory thresholds (r =.48, P =.003) were correlated. Conclusions: The effects of atropine and clonidine on rectal distensibility and sensation were significantly correlated. A preserved response to atropine suggests that reduced rectal distensibility is partly reversible, mediated by cholinergic mechanisms, and may predict the response to clonidine, providing a pharmacological challenge.
AB - Background: In order to understand the pathophysiology of rectal sensorimotor dysfunctions in women with fecal incontinence (FI) and rectal urgency, we evaluated the effects of a muscarinic antagonist and an adrenergic α2 agonist on these parameters. Methods: Firstly, rectal distensibility and sensation were evaluated with a barostat and sinusoidal oscillation at baseline and after randomization to intravenous saline or atropine in 16 healthy controls and 44 FI patients. Thereafter, FI patients were randomized to placebo or clonidine for 4 wk; rectal compliance and sensation were revaluated thereafter. The effect of atropine and clonidine on rectal functions and the relationship between them were evaluated. Results: At baseline, compared to controls, rectal capacity was lower (P =.03) while the mean pressure (P =.02) and elastance (P =.01) during sinusoidal oscillation were greater, signifying reduced distensibility, in FI. Compared to placebo, atropine increased (P ≤.02) the heart rate in controls and FI and reduced (P =.03) the variability in rectal pressures during sinusoidal oscillation in controls. Clonidine increased rectal compliance (P =.04) and reduced rectal capacity (P =.03) in FI. The effects of atropine and clonidine on compliance (r =.44, P =.003), capacity (r =.34, P =.02), pressures during sinusoidal oscillation (r =.3, P =.057), pressure (r =.6, P <.0001), and volume sensory thresholds (r =.48, P =.003) were correlated. Conclusions: The effects of atropine and clonidine on rectal distensibility and sensation were significantly correlated. A preserved response to atropine suggests that reduced rectal distensibility is partly reversible, mediated by cholinergic mechanisms, and may predict the response to clonidine, providing a pharmacological challenge.
KW - atropine
KW - clonidine
KW - fecal incontinence
KW - rectal capacity
KW - rectal compliance
KW - urgency
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U2 - 10.1111/nmo.13383
DO - 10.1111/nmo.13383
M3 - Article
C2 - 29856103
AN - SCOPUS:85053923483
SN - 1350-1925
VL - 30
JO - Neurogastroenterology and Motility
JF - Neurogastroenterology and Motility
IS - 10
M1 - e13383
ER -