Neural mechanisms of peristalsis in the isolated rabbit distal colon: a neuromechanical loop hypothesis

Published online: 16 April 2014.Propulsive contractions of circular muscle are largely responsible for the movements of content along the digestive tract. Mechanical and electrophysiological recordings of isolated colonic circular muscle have demonstrated that localized distension activates ascending and descending interneuronal pathways, evoking contraction orally and relaxation anally. These polarized enteric reflex pathways can theoretically be sequentially activated by the mechanical stimulation of the advancing contents. Here, we test the hypothesis that initiation and propagation of peristaltic contractions involves a neuromechanical loop; that is an initial gut distension activates local and oral reflex contraction and anal reflex relaxation, the subsequent movement of content then acts as new mechanical stimulus triggering sequentially reflex contractions/relaxations at each point of the gut resulting in a propulsive peristaltic contraction. In fluid filled isolated rabbit distal colon, we combined spatiotemporal mapping of gut diameter and intraluminal pressure with a new analytical method, allowing us to identify when and where active (neurally-driven) contraction or relaxation occurs. Our data indicate that gut dilation is associated with propagating peristaltic contractions, and that the associated level of dilation is greater than that preceding non-propagating contractions (2.7 ± 1.4 mm vs. 1.6 ± 1.2 mm; P < 0.0001). These propagating contractions lead to the formation of boluses that are propelled by oral active neurally driven contractions. The propelled boluses also activate neurally driven anal relaxations, in a diameter dependent manner. These data support the hypothesis that neural peristalsis is the consequence of the activation of a functional loop involving mechanical dilation which activates polarized enteric circuits. These produce propulsion of the bolus which activates further anally, polarized enteric circuits by distension, thus closing the neuromechanical loop.Phil G. Dinning, Lukasz Wiklendt, Taher Omari, John W. Arkwright, Nick J. Spencer, Simon J. H. Brookes and Marcello Cost

Characterization of the colonic response to bisacodyl in children with treatment-refractory constipation

Background: Colonic manometry with intraluminal bisacodyl infusion can be used to assess colonic neuromuscular function in children with treatment‐refractory constipation. If bisacodyl does not induce high‐amplitude propagating contractions (HAPCs), this can be an indication for surgical intervention. A detailed characterization of the colonic response to intraluminal bisacodyl in children with constipation may help to inform clinical interpretation of colonic manometry studies. / Methods: Studies were performed in five pediatric hospitals. Analysis included identification of HAPCs, reporting HAPCs characteristics, and an area under the curve (AUC) analysis. Comparisons were performed between hospitals, catheter type, placement techniques, and site of bisacodyl infusion. / Results: One hundred and sixty‐five children were included (median age 10, range 1‐17 years; n = 96 girls). One thousand eight hundred and ninety‐three HAPCs were identified in 154 children (12.3 ± 8.8 HAPCs per child, 0.32 ± 0.21 HAPCs per min; amplitude 113.6 ± 31.5 mm Hg; velocity 8.6 ± 3.8 mm/s, propagation length 368 ± 175 mm). The mean time to first HAPC following bisacodyl was 553 ± 669 s. Prior to the first HAPC, there was no change in AUC when comparing pre‐ vs post‐bisacodyl (Z = −0.53, P = .60). The majority of HAPCs terminated in a synchronous pressurization in the rectosigmoid. Defecation was associated with HAPCs (χ 2(1)=7.04, P < .01). Site of bisacodyl administration, catheter type, and hospital location did not alter the response. / Conclusions and Inferences: Intraluminal bisacodyl induced HAPCs in 93% of children with treatment‐refractory constipation. The bisacodyl response is characterized by ≥1 HAPC within 12 minutes of infusion. The majority of HAPCs terminate in a synchronous pressurization in the rectosigmoid. Optimal clinical management based upon colonic manometry findings is yet to be determined

The Ecology of Antibiotic Use in the ICU: Homogeneous Prescribing of Cefepime but Not Tazocin Selects for Antibiotic Resistant Infection

Background: Antibiotic homogeneity is thought to drive resistance but in vivo data are lacking. In this study, we determined the impact of antibiotic homogeneity per se, and of cefepime versus antipseudomonal penicillin/beta-lactamase inhibitor combinations (APP-beta), on the likelihood of infection or colonisation with antibiotic resistant bacteria and/or two commonly resistant nosocomial pathogens (methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa). A secondary question was whether antibiotic cycling was associated with adverse outcomes including mortality, length of stay, and antibiotic resistance

Coexistent faecal incontinence and constipation: A cross-sectional study of 4027 adults undergoing specialist assessment.

Background: In contrast to paediatric and geriatric populations, faecal incontinence and constipation in adults are generally considered separate entities. This may be incorrect. Methods: Cross-sectional study of consecutive patients (18-80 years) referred to a tertiary unit (2004-2016) for investigation of refractory faecal incontinence and/or constipation and meeting Rome IV core criteria (applied post-hoc) for self-reported symptoms. We sought to determine how frequently both diagnoses coexisted, how frequently coexistent diagnoses were recognised by the referring clinician and to evaluate differences in clinical characteristics between patients with single or both diagnoses. Findings: Study sample consisted of 4,027 patients (3,370 females [83·7%]). According to Rome IV criteria, 807 (20·0%) patients self-reported faecal incontinence in isolation, 1,569 (39·0%) patients had functional constipation in isolation, and 1,651 (41·0%) met criteria for both diagnoses (coexistent symptoms). In contrast, only 331 (8·2%) patients were referred for coexistent symptoms. Of the 1,651 patients with self-reported coexistent symptoms, only 225 (13·6%) were recognised by the referrer i.e. 86·4% were missed. Coexistent symptoms were most often missed in patients referred for faecal incontinence in isolation. In this group of 1,640 patients, 765 (46·7%) had concomitant symptoms of functional constipation. Opioid usage, comorbidities, childhood bowel problems, mixed incontinence symptoms, prolapse symptoms and structural abnormalities on defaecography were associated with reclassification. Interpretation: Over 40% of adults referred for anorectal physiological investigation had coexistent diagnoses of faecal incontinence and functional constipation, based on validated criteria. This overlap is overlooked by referrers, poorly documented in current literature, and may impact management

Disengaging spinal afferent nerve communication with the brain in live mice

Our understanding of how abdominal organs (like the gut) communicate with the brain, via sensory nerves, has been limited by a lack of techniques to selectively activate or inhibit populations of spinal primary afferent neurons within dorsal root ganglia (DRG), of live animals. We report a survival surgery technique in mice, where select DRG are surgically removed (unilaterally or bilaterally), without interfering with other sensory or motor nerves. Using this approach, pain responses evoked by rectal distension were abolished by bilateral lumbosacral L5-S1 DRG removal, but not thoracolumbar T13-L1 DRG removal. However, animals lacking T13-L1 or L5-S1 DRG both showed reduced pain sensitivity to distal colonic distension. Removal of DRG led to selective loss of peripheral CGRP-expressing spinal afferent axons innervating visceral organs, arising from discrete spinal segments. This method thus allows spinal segment-specific determination of sensory pathway functions in conscious, free-to-move animals, without genetic modification.Melinda A. Kyloh, Timothy J. Hibberd, Joel Castro, Andrea M. Harrington, Lee Travis, Kelsi N. Dodds, Lukasz Wiklendt, Stuart M. Brierley, Vladimir P. Zagorodnyuk and Nick J. Spence