Results of 24-h manometric recording of colonic motor activity with endoluminal instillation of bisacodyl in patients with severe chronic slow transit constipation

The aims of this study were to assess the prevalence of manometric colonic abnormalities and to evaluate the motor effect of intraluminal bisacodyl in a cohort of refractory constipated patients. Twenty-four hour colonic motility recordings were performed in 40 patients referred for a severe intractable chronic constipation. At the end of each recording session the motor effects of the endoluminal instillation of 10 mg bisacodyl were assessed. These patients were compared with 20 healthy subjects. The number of high-amplitude propagating contractions (HAPC) was significantly decreased in patients with slow transit constipation (12 +/- 11.6 vs 1 +/- 8.6, P < 0.001). Based on manometric patterns four groups of patients were isolated. Ten patients had no spontaneous HAPC, no food-induced colonic motor response and significantly lower colonic activity in transverse colon (374 +/- 1220 vs 3249 +/- 3458, P < 0.05). Five patients had significantly increased sigmoid segmental motility (20298 +/- 6364 vs 88780 +/- 3643, P < 0.001) and eight patients had significantly lower number of HAPC without other manometric abnormalities while 17 patients had normal colonic motility recordings. Endoluminal bisacodyl was able to induce HAPCs in all groups of patients. Patients with severe slow transit refractory constipation represented a heterogeneous group and endoluminal bisacodyl was able to promote a propagated motor activity in a majority of patients even in those suspected of having an inert colon.     

High amplitude propagated contractions

While most colonic motor activity is segmental and non‐propulsive, colonic high amplitude propagated contractions (HAPC) can transfer colonic contents over long distances and often precede defecation. High amplitude propagated contractions occur spontaneously, in response to pharmacological agents or colonic distention. A subset of patients with slow transit constipation have fewer HAPC. In this issue of Neurogastroenterology and Motility, Rodriguez et al. report that anal relaxation during spontaneous and bisacodyl‐induced HAPC exceeds anal relaxation during rectal distention in constipated children undergoing colonic manometry. Moreover, and consistent with a neural mechanism, anal relaxation often precedes arrival of HAPC in the left colon. High amplitude propagated contractions are also used to evaluate the motor response to a meal and pharmacological stimuli (e.g., bisacodyl, neostigmine) and to identify colonic inertia during colonic motility testing in chronic constipation. This editorial comprehensively reviews the characteristics, physiology and pharmacology of HAPC, their assessment by manometry, and relevance to constipation and diarrhea.     

In search of objective manometric criteria for colonic high-amplitude propagated pressure waves

Abstract The aims of this study were to explore all characteristics of high-amplitude propagated contractions (HAPCs) that would allow them to be distinguished from nonHAPC colonic pressure waves, and to develop computer algorithms for automated HAPC detection. Colonic manometry recordings obtained from 24 healthy volunteers were used. Automated analysis was performed to detect propagated pressure waves and to determine their amplitude, duration and area under the curve (AUC). For each of these variables distribution plots were made. Automated HAPC counts were compared to visual counts by experienced investigators. Distribution plots of 141093 colonic pressure waves lacked a bimodal pattern, as was also the case for propagated contractions (n = 8758). With increasing high-amplitude thresholds for HAPC detection, a gradual decrease in the automatically detected HAPC number was observed. These findings precluded determination of a threshold. Taking visually detected HAPCs as reference, amplitude thresholds of 100 mmHg in two channels, and 80 mmHg in one channel yielded the highest sensitivity (92%). In conclusion, objective criteria to distinguish HAPCs from other propagated pressure waves on the basis of their amplitude, duration or AUC do not exist. Automated detection of HAPCs using empirically derived criteria leads to an acceptable degree of correlation with visually detected HAPCs.     

Solid-state vs water-perfused catheters to measure colonic high-amplitude propagating contractions

Background Solid‐state (SS) manometry catheters with portable data loggers offer many potential advantages over traditional water‐perfused (WP) systems, such as prolonged recordings in a more physiologic ambulatory setting and the lack of risk for water overload. The use of SS catheters has not been evaluated in comparison with perfused catheters in children. This study aims to compare data provided by SS and WP catheters in children undergoing colonic manometry studies. Methods A SS catheter and a WP catheter were taped together such that their corresponding sensors were at the same location. Simultaneous recordings were obtained using the SS and WP catheters (both 8 channels, 10 cm apart) in 15 children with severe defecation disorders referred for colonic manometry. Signals were recorded for a minimum of 1 h during fasting, 1 h after ingestion of a meal, and 1 h after the administration of bisacodyl. Solid‐state signals from the data logger were analyzed against the perfused signals. All high‐amplitude propagated contractions (HAPCs), the most recognizable and interpreted colonic motor event, were evaluated for spatial and temporal features including their durations, amplitudes, and propagation velocities. Key Results A total of 107 HAPCs were detected with SS and 91 with WP catheters. All WP‐HAPC were also observed with SS. Linear regression analysis showed that SS catheters tended to give higher readings in the presence of amplitudes <102 mmHg and lower reading with amplitudes >102 mmHg. An opposite trend was found for the duration of contractions. No significant difference was found for HAPC velocity. Conclusions & Inferences SS catheters are more sensitive in recording HAPCs in children with defecation disorders compared with the more traditional WP assembly. There is a difference in measurements of amplitude between the two systems. Solid‐state catheters offer potential advantages over WP catheters in children, being portable, safer to use, and may provide data over a more prolonged period.     

Internal anal sphincter relaxation associated with bisacodyl‐induced colonic high amplitude propagating contractions in children with constipation: a colo‐anal reflex?

Background Describe the association of internal anal sphincter (IAS) relaxation with colonic high‐ amplitude peristaltic contractions (HAPCs). Methods Retrospective review of colon manometry tracings of children with constipation to determine the IAS relaxation characteristics associated with HAPC’s (HAPC‐IASR) events and compare them to the those seen during the performance of the anorectal manometry (ARMRAIR) events. Key Results A total of 70 HAPC‐ IASRs were observed in 15 patients, 65 after bisacodyl, two during fasting and three after a meal. In 64% of events, the IAS relaxation started when the HAPC reached left colon and in 36% as proximal as the hepatic flexure. High‐ amplitude peristaltic contraction propagation seems to be important in HAPC‐IASR characteristics; those propagating distal to sigmoid colon demonstrated larger and longer IAS relaxation as well as lower residual pressure, but equivalent resting pressure compared with HAPC’s ending proximal to sigmoid colon. Although IAS resting pressure was comparable for ARM‐RAIRs and HAPC‐IASRs, the duration and magnitude of anal relaxation was higher, and the anal residual pressure was lower in HAPC‐IASRs. Conclusions & Inferences We demonstrated that IAS relaxation in constipated children is associated with HAPCs migrating in the proximal and distal colon; in most cases, starting when peristalsis is migrating through left colon and in an important proportion while migrating proximally. We also demonstrated that HAPC‐IASRs are different from ARM‐RAIRs suggesting a neurally mediated reflex. Finally, the IAS relaxation characteristics are highly dependent on the degree of propagation of HAPCs, which could have important implications in the understanding of defecation disorders.     

Fermentation of starch stimulates propagated contractions in the human colon

Background In healthy humans, up to 30 g of daily ingested starch escape small intestinal digestion, and are fermented in the colon. This physiological starch malabsorption could modify colonic motility through metabolites such as short‐chain fatty acids produced by fermentation. Methods Ten healthy volunteers swallowed a probe, consisting of an infusion catheter, six perfused catheters and a balloon connected to a barostat. On two consecutive days colonic motility was recorded in fasting subjects in the basal state (1 h), and then during (3 h), and after (2 h) the intracolonic infusion of 750 mL of isoosmotic and isovolumetric solutions containing sodium chloride with or without 15 g wheat starch. We determined (i) the volume of hydrogen and methane exhaled in breath, (ii) a global motility index and the number of high amplitude propagated contractions (HAPCs), and (iii) the mean balloon volume, reflecting the tonic motor activity. Key Results [median (IQR)] Compared to the basal period, colonic infusion of starch or saline did not modify the colonic motility index and tone. However, the number of HAPCs was significantly higher during and after infusion of starch than of saline [4.5 (2.75–6.5) vs 0.96 (0–2.66)/5 h, starch vs saline respectively; P = 0.011]. Conclusions & Inferences In healthy humans, colonic fermentation of a physiological malabsorbed amount of starch has no effect on the tonic and phasic colonic motor activities, but produces a significant increase in the number of HAPCs. This may participate in the physiological propulsion of colonic contents.     

Effect of extrinsic denervation on muscarinic neurotransmission in the canine ileocolonic region

To explore the hypothesis that denervation hypersensitivity increases ileocolonic motor activity after extrinsic denervation, we compared muscarinic neurotransmission in canine ileocolonic loops that were isolated and either extrinsically innervated or extrinsically denervated. We recorded ileal, ileocolonic sphincter (ICS) and colonic pressures, and colonic tone, compliance and relaxation during ileal distention. Muscarinic effects were probed by neostigmine, and minimally effective doses of muscarinic receptor antagonists. Denervation augmented ileal, ICS and colonic contractile activity; colonic high-amplitude propagating contractions (HAPCs) were also augmented; colonic relaxation during ileal distention was abolished. Neostigmine induced HAPCs in both loop preparations. Pirenzipine (M1 antagonist) reduced ileal contractile activity in all loops and reduced colonic relaxation during ileal distention in innervated loops. Pirenzipine also reduced colonic tone and colonic HAPCs, more in denervated loops. Darifenacin (M3 antagonist) reduced ileocolonic contractile activity and tone more than did AF-DX 116 (M2 antagonist) in all loops. Cholinergic receptor subtypes modulate different facets of ileocolonic motor activity in the canine ileocolonic region. Increased sensitivity at M1 muscarinic receptors may partly account for the effects of extrinsic denervation.     

Ileal manometry in children following ileostomies and pull-through operations

Our aim was to analyse the patterns of ileal contractions in children. We reviewed the charts of 23 children who had ileal manometry studies (16 males), mean age 7 years (range 2 months to 17 years). We positioned the manometry catheters with 4-8 recording sites, 5 or 15 cm apart, through ileostomies fashioned for clinically indicated reasons. We studied six additional children with persistent faecal soiling following endorectal pull through for Hirschsprung's disease; the catheters were positioned through the anus and colon into the ileum. We recorded phasic and tonic intermittent contractions in all the subjects, clustered contractions (rate 5-9 min-1, duration 20-120 s) in 19 subjects with ileostomies and four with endorectal pull throughs. In 13 children there were prolonged propagated contractions, > 60 mmHg in amplitude, > 15 s in duration, propagating at rates of 2-6 cm s-1 over at least 20 cm. The migrating motor complex was rare; in 55 h of fasting recording there were two phase III sequences. There are four distinctive features of ileal manometry recordings in children: random intermittent contractions, clustered contractions, prolonged propagated contractions and tonic contractions. The features of ileal motility differ from motility in the proximal small bowel.     

Factors associated with successful decrease and discontinuation of antegrade continence enemas (ACE) in children with defecation disorders: a study evaluating the effect of ACE on colon motility

Background Antegrade continence enemas (ACE) have been used in the treatment of defecation disorders in children; little is known on their effect on colon motility and the utility of the colon manometry (CM) predicting long‐term ACE outcomes. Methods Retrospective review of children with constipation undergoing CM before and after ACE to evaluate CM changes and their utility on predicting ACE outcome. Key Results A total of 40 patients (mean age 8.8 SD 3 years and 53% female patients) were included; 39 of 40 responded to the ACE. Of these 39, 14 (36%) were dependent and 25 (64%) had decreased it (11 of those or 28% discontinued it). On repeat CM we found a significant increase in the fasting (P < 0.01) and postprandial (P = 0.03) motility index, number of bisacodyl‐induced high amplitude propagating contractions (HAPCs) (P = 0.03), and total HAPCs (P = 0.02). Gastrocolonic response to a meal, propagation and normalization of HAPCs improved in 28%, 58%, and 33%, respectively, with CM normalizing in 33% of patients. The baseline CM did not predict ACE outcome. The presence of normal HAPCs on the repeat CM was associated with ACE decrease. Progression and normalization of HAPCs (P = 0.01 and 0.02, respectively) and CM normalization (P = 0.01) on repeat CM were individually associated with ACE decrease. No CM change was associated with ACE discontinuation. Multivariate analysis showed that older age and HAPC normalization on CM predict ACE decrease and older age is the only predictor for ACE discontinuation. Conclusions & Inferences Colon motility improves after ACE and the changes on the repeat CM may assist in predicting ACE outcome.     

Comparison of simultaneous recordings of human colonic contractions by manometry and a barostat

Abstract Our hypothesis was that manometry in the colon was less sensitive than the electronic barostat in detection of colonic contractions. In ten healthy volunteers, we have characterised the pressure activity and tone of the colon by means of combined multilumen manometry and a barostatic balloon that was infinitely compliant, conformed to the colon's inner wall, and was clamped at a constant 'operating' pressure throughout the study. A computer program separated indices of the colon's motor function detected by the barostat: a baseline volume and phasic volume events. The barostat detects on average 70% more phasic pressure events than manometric sideholes located 2 em proximal to 7 cm distal to the balloon. Manometry becomes less sensitive than the barostat when the colonic diameter exceeds 5.6 em. The barostat detects on average 90% of all propagated and non-propagated (>30 mmHg) manometric peaks. The baseline volume changes significantly after the ingestion of a 1000-kcal meal, consistent with an increment in colonic tone, undetected by manometry. A combined barostat—manometry assembly appears to be preferable to manometry alone in the intraluminal evaluation of human colonic pressure activity and tone.     

High‐resolution colonic manometry accurately predicts colonic neuromuscular pathological phenotype in pediatric slow transit constipation

Background Severe pediatric slow transit constipation (STC) is commonly due to intrinsic colonic neuromuscular disease. We sought to correlate neuromuscular histological phenotypes in pediatric STC with colonic manometric phenotypes using high‐resolution manometry (HRM). We tested the hypothesis that failure of motor quiescence (FQ) between bisacodyl‐induced high amplitude propagating sequences (HAPSs) might predict neuromuscular pathology. Methods Eighteen children (10 males, median age: 7.5 years) with refractory STC underwent stationary colonic HRM before segmental colonic resection. Six age‐matched constipated children with normal colonic transit served as controls. Colonic resection specimens underwent histopathological analysis. Conventional manometric parameters and area under the curve (AUC) during a 1‐min period following bisacodyl‐induced HAPSs [PBAUC₁], as measure of FQ, were calculated. Key Results Numbers of postbisacodyl HAPSs in descending and sigmoid segments were lower in patients than controls (P < 0.01, respectively). Low amplitude propagating sequences (LAPSs) were common prebisacodyl in controls and rare in STC (P < 0.001), whereas postbisacodyl LAPS were more common in STC (P < 0.001). Postbisacodyl, both retrograde propagating contractions and bursts of contractions were present in STC patients only (P < 0.001 and P < 0.01). Postbisacodyl simultaneous pressurization was seen only in STC (P < 0.05 and P < 0.001, in descending and rectosigmoid segments). Histological abnormalities were present in 17/18. Fourteen were neurogenic, one neuro‐myogenic, and two myogenic. In segments with HAPS, PBAUC₁ was predictive of colonic neuropathy using a cutoff of 205 mmHg.s^‐1 (Sensitivity 100%, specificity 86%, PPV92%, NPV100%). Conclusions & Inferences PBAUC₁ is increased in multiple colonic segments in neuropathic pediatric STC and constitutes a sensitive and specific biomarker of neuropathy.     

Proximal colonic propagating pressure waves sequences and their relationship with movements of content in the proximal human colon

Abstract  Abnormal colonic motor patterns have been implicated in the pathogenesis of severe constipation. Yet in health, the mechanical link between movement of colonic content and regional pressures have only been partially defined. This is largely due to current methodological limitations. Utilizing a combination of simultaneous colonic manometry, high-resolution scintigraphy and a quantitative technique for detecting discrete episodic flow, our aim was to examine the propulsive properties of colonic propagating sequences (PS) in the healthy colon. In six healthy volunteers a nasocolonic manometry catheter was positioned to record colonic pressures at 7.5 cm intervals from terminal ileum to the splenic flexure. With subjects positioned under a gamma camera, 30 MBq of ^99mTc sulfur colloid was instilled into the terminal ileum, 22.5 cm proximal to the ileocolonic junction. Isotopic images were recorded (10 s/frame) and synchronized with the manometric trace. In the proximal colon we identified 137 antegrade PSs, of which 93% were deemed to be associated temporally with movements of luminal content. Low amplitude PSs, with component pressure waves between 2 mmHg and 5 mmHg, were as likely to be associated with colonic movements as higher amplitude PSs. As such there was no correlation between the amplitude of the PS and the temporal relationship with colonic movements. Within the proximal colon, 24 retrograde PSs were identified, 23 of which were associated with retrograde movements of colonic content. We conclude that proximal colonic PSs are highly propulsive and are a major determinant of proximal colonic flow.     

Does magnetic stimulation of sacral nerve roots modify colonic motility? Results of a randomized double‐blind sham‐controlled study

Abstract  Although sacral nerve root stimulation (SNS) can result in a symptomatic improvement of faecal incontinence, the mechanism of action remains unknown. The aim of this study was to assess whether short-term magnetic SNS can inhibit pharmacologically induced propulsive colonic contractions. Twelve healthy volunteers (median age: 43.5 years old) were studied on two separate occasions and randomized into either active (15 Hz, 100% output intensity for 5 s min⁻¹ for 30 min) or sham rapid rate lumbosacral magnetic stimulation (rLSMS). Colorectal motility was recorded with a manometric catheter located at the most proximal transducer in the left colon and the most distal, in the rectum. Colonic contractions were provoked by instilling Bisacodyl. The effects of rLSMS on colonic, sigmoid and rectal contractions were monitored and recorded after Bisacodyl instillation. The appearance of high-amplitude contractions propagated or not (HAC/HAPC) provoked by Bisacodyl instillation was significantly delayed during active compared to sham stimulation ( P  = 0.03). There was no difference in the characteristics of HAC/HAPC (i.e. frequency, amplitude, duration, velocity of propagation) or the motility index with active or sham stimulation. The perception of urgency tended to be decreased with rLSMS following Bisacodyl instillation. The catheter was expulsed within a median of 16.5 min (range 8–39) after Bisacodyl administration during active stimulation compared to 14 min (range 5–40) during sham stimulation ( P  = 0.03). This study suggests that rLSMS could delay the appearance of the first Bisacodyl-induced colonic contractions.     

Role of motility in chronic diarrhoea

Patients complaining of 'chronic diarrhoea' usually mean the passage of loose, urgent stools. Chronic diarrhoea is a feature of malabsorption; it may also be seen in the 'dumping syndrome' which follows gastric surgery, small intestinal bacterial overgrowth, bile salt malabsorption and in malabsorption of simple sugars including most commonly lactose, fructose and sorbitol. Excessively rapid entry of chyme into the small or large intestine generates propulsive motor patterns leading to accelerated transit. Inflammation is associated with decreased normal mixing motor patterns but increased propulsive motility including high amplitude propagated contractions (HAPCs). Evidence for abnormal small intestinal motility in the diarrhoea associated with irritable bowel syndrome (IBS) is conflicting and any difference appears small. Increased colonic HAPCs with increased propulsion is seen in IBS with diarrhoea (IBS-D). Stress-induced colonic motility is increased in IBS-D with hyper-responsiveness to corticotrophin releasing factor (CRF). Long-lasting increases in mucosal serotonin availability may contribute to the chronic diarrhoea seen in IBS-D and coeliac disease. Treatments for abnormal motility in chronic diarrhoea include those designed to correct specific underlying abnormalities including octreotide, antibiotics, colestyramine, specific food avoidance and anti-inflammatory agents. There are also treatments aimed primarily at altering motility directly including opiates, 5HT3 receptor antagonists and amitriptyline.     

Functional Role of the Equine Ileocecal Sphincter

Recordings of intraluminal pressure at the equine ileocecal junction indicate the presence of a high-pressure zone of about 6 mm Hg over a distance of 5 cm. Both cecal distention by air and acidification of cecal contents by short-chain fatty acids elicited bursts of phasic pressure waves at the ileocecal junction. Phasic contractions contributed to the concomitant increase of tone at the ileocecal junction. Reflux of acidic cecal contents into the ileum was immediately counteracted by propagated phasic contractions. It appears that contractions propagated toward the cecum, rather than stationary contractions, contribute to the sphincteric properties at the ileocecal junction. The patterns of motor activity of the ileocecal region in species with a well-developed cecum suggest the additional presence of numerous propagated contractions of cecal origin.     

Day‐to‐day reproducibility of prolonged ambulatory colonic manometry in healthy subjects

Background Although colonic manometry provides useful information regarding colonic physiology, considerable variability has been reported both for regional motility and manometric patterns. Whether colonic manometry is reproducible is not known. Methods Seven healthy volunteers (three men, four women, mean age = 34 years) underwent two studies of 24‐h ambulatory colonic manometry, each 2 weeks apart. Manometry was performed by placing a six‐sensor solid‐state probe, up to the hepatic flexure and anchored to colonic mucosa. Colonic motility was assessed by the number and area‐under‐curve (AUC) of pressure waves and motility patterns such as high‐amplitude propagating contractions (HAPC). Waking and meal‐induced gastrocolonic responses were also assessed. Paired t‐test was used to examine the reproducibility and intra and interindividual variability. Key Results The number of pressure waves and propagating pressure waves and HAPC, and AUC were similar between the two studies. Diurnal variation, waking and meal‐induced gastrocolonic responses were also reproducible. There was some variability in the incidence of individual colonic motor patterns. Conclusions & Inferences Colonic manometry findings were generally reproducible, particularly for the assessment of key physiologic changes, such as meal‐induced gastrocolonic, HAPC, and waking responses.     

The relationship between propagated contractions and pseudoaffective changes in blood pressure in response to intestinal distension

We investigated the relationship between changes in small intestinal motility and changes in blood pressure and heart rate in response to intestinal distension. Rats were maintained under stable anaesthesia with alpha-chloralose, and jejunal motility, blood pressure and heart rate were recorded. Pressure changes during propagated contractions of the circular muscle were recorded in the jejunum when the intraluminal pressure was maintained at 10 mmHg. Raising the pressure in 10 mmHg increments from 10 mmHg to 40 mmHg increased the frequency of propagated contractions from 0.30 +/- 0.06 min-1 (mean +/- SEM) to 1.29 +/- 0.09 per min. In contrast, amplitudes of contractions above baseline pressure decreased from 19.5 +/- 0.6 mmHg to 7.8 +/- 0.5 mmHg. Simultaneously, blood pressure and heart rate were both increased. Pretreatment of rats with capsaicin, or severing the mesenteric nerves acutely, prevented these cardiovascular responses, but did not influence the changes in propagated activity caused by distension. Propagated contractions were blocked by hexamethonium (10 mg kg-1, intravenously [i.v.]) and by local application of 2% lidocaine, but propulsion was unchanged by hyoscine (1 mg kg-1, i.v.). Phentolamine (1 mg kg-1, i.v.) increased the frequency of propagated contractions. The methods described in this work allow the effects of drugs on intrinsic intestinal reflexes to be distinguished from their effects on extra-intestinal, pseudoaffective reflexes. In addition, unlike other experiments using anaesthetized rats, blood pressure increased in response to distension, as it does in mammals that are not anaesthetized. The experiments demonstrate that the neural pathways for propagated contractions that rely on intrinsic nerve circuits, including intrinsic primary afferent neurones, and the neural pathways for extrinsic reflexes that signal pain or discomfort in the intestine, which involve capsaicin-sensitive spinal afferent neurones, are independent.     

Oxytocin stimulates colonic motor activity in healthy women

The effects of oxytocin in the gastrointestinal tract are unclear. The aim of this study was to examine the effect of infusion of oxytocin on colonic motility and sensitivity in healthy women. Fourteen healthy women were investigated twice. A 6-channel perfusion catheter, with three recording points (2 cm apart) proximally and three recording points distally to a barostat balloon, was inserted to the splenic flexure. An intestinal feeding tube was placed in the mid-duodenum. A 90-min duodenal lipid infusion of 3 kcal min(-1) was administered. Thirty minutes after the start of the lipid infusion, the subject randomly received either 20 or 40 mU min(-1) of oxytocin, or isotonic saline as intravenous infusions for 90 min. Meanwhile, the colonic motility was recorded. During the last 30 min of oxytocin and saline infusion, the visceral sensitivity to balloon distensions was examined. During lipid infusion the number of antegrade contractions per hour was 0.7 +/- 0.3 after saline and 3.9 +/- 1.4 after oxytocin (P = 0.03), indicating more pronounced lumen-occlusive contractile activity after oxytocin administration. Some of these consisted of high-amplitude (> 103 mmHg in amplitude) antegrade contractions. Lipid infusion evoked a decrease of the balloon volume, reflecting increased colonic tone, but there was no difference between saline and oxytocin. Sensory thresholds did not differ significantly between saline and oxytocin. Infusion of oxytocin stimulates antegrade peristaltic contractions in stimulated colon in healthy women. The effects of oxytocin on colonic motor activity deserve to be further explored, especially in patients with colonic peristaltic dysfunction.     

Stimulatory action of mitemcinal (GM-611), an acid-resistant non-peptide motilin receptor agonist, on colonic motor activity and defecation: spontaneous and mitemcinal-induced giant migrating contractions during defecation in dogs

Abstract  The aim of this study was to characterize giant migrating contractions (GMCs) during spontaneous defecation in dogs and to investigate the effect of mitemcinal (an orally active and highly acid-resistant motilin receptor agonist) on colonic motility to assess the possibility of using it for the treatment of colonic motility disorders. To assess colonic motility, strain-gauge force transducers were implanted on the gastrointestinal tract of five dogs, and the behaviour of the dogs was monitored with a noctovision-video camera system. The effect of mitemcinal (0, 3, 10 or 30 mg per dog) and sennoside (300 mg per dog) on colonic motility was assessed 24 h after oral administration. During a 39-day period, the starting point of most of the 140 GMCs was between the transverse colon and the descending colon, but some variation was observed. In the daytime, the GMCs originated from somewhat more proximal positions than at night. Mitemcinal caused an increase in the GMC-index (integration of contractile amplitude and duration) and proximal translocation of the GMC starting point, but did not cause an increase in the number of defecations 12 h after administration. Sennoside, however, caused a significant increase in the number of defecations, an increase in the GMC-index, and prolongation of the duration of GMCs. The GMC starting point in the canine colon varied during spontaneous defecation. Mitemcinal was a potent prokinetic drug to mimic a spontaneous defecation compared with sennoside. Mitemcinal evacuates more intestinal luminal contents during the defecation than does sennoside.