Colonic Motor Activity Research Articles

Anorectal Stimulation Causes Increased Colonic Motor Activity in Subjects With Spinal Cord Injury

Background: Difficulty with evacuation (DWE) is a major problem after spinal cord injury (SCI). Stimulation of the anal canal and lower rectum, accomplished using a gloved finger (so-called digital rectal stimulation or DRS) is often used as an adjunct to laxatives and enemas to facilitate bowel evacuation. However, the basis for the efficacy of DRS is not known. This study assessed the effect of DRS on colonic motility.Methods: Six subjects with SCI were studied several hours after a bowel care session. Colonic motility was assessed using a manometric catheter (affixed endoscopically to the splenic flexure) at baseline, during DRS, and after DRS. In addition, evacuation of barium oatmeal paste (with the consistency of stool and introduced into the rectum and descending colon) was assessed simultaneously using fluoroscopic techniques.Results: The mean number (± SEM) of peristaltic waves per minute increased from 0 at baseline to 1.9 (±0.5/min) during DRS and 1.5 (±0.3/min) during the period immediately after cessation of DRS (P <0.05). The mean amplitude (±SEM) of the peristaltic contractions was 43.4 (±2.2) mmHg. The frequency of contractions, as well as amplitude of contractions, during or immediately after DRS was not significantly different. These manometric changes in response to DRS were accompanied by expulsion of barium oatmeal paste in every subject by the fifth DRS.Conclusions: DRS causes left-sided colonic activity in subjects with SCI. At least in part, an anorectal colonic reflex that results in enhanced contractions of the descending colon and rectum may contribute to bowel evacuation in individuals with SCI.

CCK 2 receptors mediate inhibitory effects of cholecystokinin on the motor activity of guinea-pig distal colon

Cholecystokinin and related peptides are involved in the control of intestinal motility and cholecystokinin receptor ligands might represent new pharmacological tools for the treatment of symptoms associated with functional bowel disorders. However, the respective roles played by cholecystokinin receptor subtypes and the mechanisms underlying these regulatory actions remain undetermined. This study was designed to examine the influence of cholecystokinin receptor subtypes on the motor activity of guinea-pig distal colon. The effects of drugs acting on CCK 1 and CCK 2 receptors were assessed in vitro on the contractile activity of longitudinal smooth muscle, both under basal conditions and in the presence of transmural electrical stimulation or KCl-induced contractions. The application of cholecystokinin octapeptide sulphate (cholecystokinin-8S) to colonic preparations induced concentration-dependent contractions which were prevented by devazepide (CCK 1 receptor antagonist), enhanced by GV150013 (CCK 2 receptor antagonist) or N ω -nitro- l-arginine methylester ( l-NAME, nitric oxide synthase inhibitor), and unaffected by tetrodotoxin. The application of gastrin-17 to colonic preparations resulted in relaxant responses which were insensitive to devazepide, and prevented by GV150013, l-NAME or tetrodotoxin. l-NAME, N ω -propyl- l-arginine (NPA, neuronal nitric oxide synthase inhibitor) or GV150013 enhanced electrically evoked contractile responses, whereas devazepide did not. When tested in the presence of l-NAME or NPA the enhancing effect of GV150013 on electrically induced contractions no longer occurred. In the presence of KCl-induced pre-contractions, cholecystokinin-8S or gastrin-17 evoked concentration-dependent relaxations, which were unaffected by devazepide and were counteracted by GV150013, l-NAME, NPA or tetrodotoxin. In conclusion, the present results indicate that, at level of distal colon, CCK 1 receptors mediate direct contractile effects on smooth muscle, whereas CCK 2 receptors on enteric neurons mediate relaxant responses via nitric oxide release.

Increased presence of serotonin-producing cells in colons with diverticular disease may indicate involvement in the pathophysiology of the condition

Serotonin is an important neuroendocrine transmitter participating in the control of colonic motor activity through neural and biochemical mechanisms in the Enteric Nervous System (ENS). A possible pathophysiological factor for diverticular disease (DD) is altered colonic motility. The study compared the distribution of serotonin cells (SC) in the colonic mucosa of patients with diverticular disease to controls. Sixteen paraffin specimens with sigmoid diverticular disease were selected and sections of bowel without diverticula from the same specimen were used as its own control. The resection margins from sixteen colonic specimens excised for sigmoid cancer were additional controls. Immunocytochemical staining for serotonin cells was performed on 4-mum tissue sections with polyclonal antibody (NCL-SEROTp). The number of serotonin-positive cells per ten microscopic fields (x200) was assessed in all groups and the staining distribution was defined as low (0-33%), moderate (>33-66%) and high (>66%) according to the percentage of the entire cell containing contrast material. The control specimens were blinded before analysis. Student's t test was used for statistical analysis and significance level was set as P < 0.05. The mean number of serotonin-positive cells per ten fields in the colonic mucosa of specimens with diverticular disease was significantly higher [252.44 (SD 90.64)] than the specimen's own control [147.31 (SD 50.16)] and at normal resection margins of cancer specimens [228.38 (SD 120.10)]. The paired analysis between diverticular disease specimens and its own control (paired t test) showed significant differences for moderate (P = 0.008), high (P = 0.001) and total (P = 0.002) number of serotonin cells. There was no evidence of significance between mean DD and cancer values. Increased presence of SCs and the higher proportion of high and moderate staining cells (indicating increased hormone content) indicate the possible role of serotonin in DD. This may be contributing to the pathogenesis of the condition by altered colonic motility in the affected segments in a similar way as in irritable bowel syndrome.

Activation of neural circuitry and Ca2+ waves in longitudinal and circular muscle during CMMCs and the consequences of rectal aganglionosis in mice

In mammals that develop rectal aganglionosis, the aganglionic segment still exhibits spontaneous phasic contractions that contribute to dysmotility and pseudoobstruction in this region. However, almost nothing is known about the mechanisms that generate these myogenic contractions or the effects of aganglionosis on the generation of Ca(2+) waves that underlie contractions of the longitudinal muscle (LM) and circular muscle (CM). In a mouse model of Hirschsprung's disease [endothelin type B receptor-deficient (Ednrb(s-l)/Ednrb(s-l)) mice], the Ca(2+) indicator fluo-4 was used to simultaneously monitor the temporal activation and spread of intercellular Ca(2+) waves in the LM and CM during spontaneous colonic motor activities. During the intervals between colonic migrating motor complexes (CMMCs) in control mice, Ca(2+) waves discharged asynchronously between the LM and CM. However, in these same mice, during CMMCs, a burst of discreet Ca(2+) waves fired simultaneously in both muscle layers, where the propagation velocity of Ca(2+) waves significantly increased, as did the rate of initiation and number of collisions between Ca(2+) waves. Hexamethonium (300 microM) or atropine (1 microM) prevented synchronized firing of Ca(2+) waves. In the aganglionic distal colon of Ednrb(s-l)/Ednrb(s-l) mice, not only were CMMCs absent, but Ca(2+) waves between the two muscle layers fired asynchronously, despite increased propagation velocity. The generation of CMMCs in control mice involves synchronized firing of enteric motor nerves to both the LM and CM, explaining the synchronized firing of discreet Ca(2+) waves between the two muscle layers. Aganglionosis results in a sporadic and sustained asynchrony in Ca(2+) wave firing between the LM and CM and an absence of CMMCs.

5-Hydroxytryptophan activates colonic myenteric neurons and propulsive motor function through 5-HT4receptors in conscious mice

Serotonin [5-hydroxytryptamine (5-HT)] acts as a modulator of colonic motility and secretion. We characterized the action of the 5-HT precursor 5-hydroxytryptophan (5-HTP) on colonic myenteric neurons and propulsive motor activity in conscious mice. Fos immunoreactivity (IR), used as a marker of neuronal activation, was monitored in longitudinal muscle/myenteric plexus whole mount preparations of the distal colon 90 min after an intraperitoneal injection of 5-HTP. Double staining of Fos IR with peripheral choline acetyltransferase (pChAT) IR or NADPH-diaphorase activity was performed. The injection of 5-HTP (0.5, 1, 5, or 10 mg/kg ip) increased fecal pellet output and fluid content in a dose-related manner, with a peak response observed within the first 15 min postinjection. 5-HTP (0.5-10 mg/kg) dose dependently increased Fos expression in myenteric neurons, with a maximal response of 9.9 +/- 1.0 cells/ganglion [P < 0.05 vs. vehicle-treated mice (2.3 +/- 0.6 cells/ganglion)]. There was a positive correlation between Fos expression and fecal output. Of Fos-positive ganglionic cells, 40 +/- 4% were also pChAT positive and 21 +/- 5% were NADPH-diaphorase positive in response to 5-HTP, respectively. 5-HTP-induced defecation and Fos expression were completely prevented by pretreatment with the selective 5-HT4 antagonist RS-39604. These results show that 5-HTP injected peripherally increases Fos expression in different populations of cholinergic and nitrergic myenteric neurons in the distal colon and stimulates propulsive colonic motor function through 5-HT4 receptors in conscious mice. These findings suggest an important role of activation of colonic myenteric neurons in the 5-HT4 receptor-mediated colonic propulsive motor response.

Interstitial Cells of Cajal in Patients With Constipation due to Total Colonic Inertia

Colonic wall contains interstitial cells of Cajal. In view of studies demonstrating that Cajal cells generate electric waves which are presumably responsible for colonic motor activity, and that these waves are absent in total colonic inertia, we investigated the hypothesis that colonic Cajal cells might be disordered in patients with total colonic inertia. The study comprised 28 patients (age 41.6 ± 8.2 SD years, 19 women, 9 men) with total colonic inertia in whom total colectomy was performed. Colonic specimens obtained from normal segments of the excised colon of 24 cancer patients acted as controls. Specimens were subjected to c-kit immunohistochemistry. Controls for antisera specificity consisted of tissue incubated with normal rabbit serum that had been substituted for the primary antiserum. C-kit-positive branched Cajal-like cells were detected in the musculature of the normal colonic segments. They were distinguishable from the C-kit-negative smooth muscle cells and the C-kit-positive but unbranched mast cells. No Cajal cells were detected in colon of total colonic inertia patients. The absence of Cajal cells in patients with total colonic inertia can be assumed to explain the absence of electric waves and motile activity previously reported in these patients. Further studies are needed to investigate the cause of Cajal-cell absence.

Anatomic modifications in the enteric nervous system of piebald mice and physiological consequences to colonic motor activity

It has been assumed that in piebald lethal mice that develop megacolon, impaired colonic motor activity is restricted to the aganglionic distal colon. Peristaltic mechanical recordings, immunohistochemistry, and quantitative PCR were used to investigate whether regions of the colon, other than the aganglionic segment, may also show anatomical modifications and dysfunctional colonic motor activity. Contrary to expectations, colonic migrating motor complexes (MMCs) were absent along the whole colon of piebald lethal homozygote mice and severely impaired in heterozygote siblings. Aganglionosis was detected not only in the distal colon of piebald homozygote lethal mice (mean length: 20.4 +/- 2.1 mm) but also surprisingly in their heterozygote siblings (mean length: 12.4 +/- 1.1 mm). Unlike homozygote lethal mice, piebald heterozygotes showed no signs of megacolon. Interestingly, mRNA expression for PGP 9.5 was also dramatically reduced (by 71-99%) throughout the entire small and large bowel in both homozygote lethal and heterozygous littermates (by 67-87%). Histochemical staining confirmed a significant reduction in myenteric ganglia along the whole colon. In summary, the piebald mutation in homozygote lethal and heterozygote siblings is associated with dramatic reductions in myenteric ganglia throughout the entire colon and not limited to the distal colon as originally thought. Functionally, this results in an absence or severe impairment of colonic MMC activity in both piebald homozygote lethal and heterozygote siblings, respectively. The observation that piebald heterozygotes have an aganglionic distal colon (mean length: 12 mm) but live a normal murine life span without megacolon suggests that aganglionosis >12 mm and the complete absence of colonic MMCs may be required before any symptoms of megacolon arise.

Corticotropin-Releasing Hormone Receptor 1 Antagonist Blocks Brain–Gut Activation Induced by Colonic Distention in Rats

The corticotropin-releasing hormone receptor 1 mediates stress-induced changes in colonic motor activity and emotion. We tested the hypothesis that pretreatment with JTC-017, a specific corticotropin-releasing hormone receptor 1 antagonist, blocks colorectal distention-induced hippocampal noradrenaline release and visceral perception in rats. We also investigated whether pretreatment with JTC-017 blocks acute or chronic colorectal distention-induced adrenocorticotropic hormone release, anxiety, and stress-induced changes in colonic motility. Rats were pretreated intrahippocampally with alpha-helical corticotropin-releasing hormone (1.25 microg/kg; vehicle), a nonspecific corticotropin-releasing hormone receptor antagonist, or intraperitoneally with JTC-017 (10 mg/kg). Hippocampal noradrenaline release after microdialysis and the frequency of abdominal contractions were measured in response to acute colorectal distention. Plasma adrenocorticotropic hormone levels, anxiety-related behavior, and stress-induced changes in colonic motility were evaluated after acute or chronic colorectal distention followed by exposure to an elevated plus maze. Administration of alpha-helical corticotropin-releasing hormone or JTC-017 significantly attenuated hippocampal noradrenaline release and reduced the frequency of abdominal contractions induced by acute distention. In addition, JTC-017 significantly reduced plasma adrenocorticotropic hormone and anxiety after acute distention. After chronic distention, changes in plasma adrenocorticotropic hormone and anxiety were not significant because of habituation. In contrast, a significant increase in fecal pellet output during the elevated plus maze was observed after chronic distention. This increase in fecal pellet output was blocked by pretreatment with JTC-017. Our results suggest that JTC-017, a specific corticotropin-releasing hormone receptor 1 antagonist, attenuates hippocampal noradrenaline release, visceral perception, adrenocorticotropic hormone release, and anxiety after acute colorectal distention in rats. In addition, JTC-017 blocks stress-induced changes in colonic motility after chronic colorectal distention in rats.

Colonic manometry via appendicostomy shows reduced frequency, amplitude, and length of propagating sequences in children with slow-transit constipation

Background/Purpose We wish to define colonic motor function in children with slow-transit constipation (STC) using manometry catheters introduced through appendiceal stomas, previously sited for controlling fecal retention by colonic irrigation. Methods We undertook 24-hour pancolonic manometry of 6 children (5 boys; mean, 11.5 years; SD, 3.0) using a multilumen silastic catheter. Results were compared to nasocolonic motility studies obtained in healthy young adults. Results Antegrade propagating sequences (APSs) originated less frequently in the cecum compared to controls. There were fewer APS (mean ± SEM: STC, 13 ± 6 per 24 hours; controls, 52 ± 6 per 24 hours; P < .01) and high-amplitude propagating contractions (HAPCs: STC, 5 ± 2 per 24 hours; controls, 9.9 ± 1.4 per 24 hours; P < .05). The amplitude of APS and HAPC was less in STC (APS, 39 ± 9 mm Hg; controls, 54 ± 3 per 24 hours; P < .05) (HAPC: STC, 94 ± 10 mm Hg; control, 117 ± 3 mm Hg; P < .01), whereas the amplitude of retrograde propagating sequences was greater in STC (43 ± 6 mm Hg; control, 27 ± 1 mm Hg; P < .01). The distances propagated by HAPC were significantly less in STC (36 ± 4.5 vs 47 ± 2.3 cm, controls; P < .05), and there was no evidence of a region-specific difference in propagation velocity of APS. Neither meal ingestion nor waking significantly increased colonic motor activity in patients with STC. Conclusions Despite the small numbers available to be studied, we found that children with STC in whom an appendicostomy had been placed show significant abnormalities in pancolonic motor function.

Stress and the gastrointestinal tract

Stress, defined as an acute threat to homeostasis, evokes an adaptive or allostatic response and can have both a short- and long-term influence on the function of the gastrointestinal tract. The enteric nervous system is connected bidirectionally to the brain by parasympathetic and sympathetic pathways forming the brain-gut axis. The neural network of the brain, which generates the stress response, is called the central stress circuitry and includes the paraventricular nucleus of the hypothalamus, amygdala and periaqueductal gray. It receives input from the somatic and visceral afferent pathways and also from the visceral motor cortex including the medial prefrontal, anterior cingulate and insular cortex. The output of this central stress circuit is called the emotional motor system and includes automatic efferents, the hypothalamus-pituitary-adrenal axis and pain modulatory systems. Severe or long-term stress can induce long-term alteration in the stress response (plasticity). Corticotropin releasing factor (CRF) is a key mediator of the central stress response. Two CRF receptor subtypes, R1 and R2, have been described. They mediate increased colonic motor activity and slowed gastric emptying, respectively, in response to stress. Specific CRF receptor antagonists injected into the 0 block these visceral manifestations of stress. Circulating glucocorticoids exert an inhibitory effect on the stress response by receptors located in the medial prefrontal cortex and hippocampus. Many other neurotransmitters and neuroimmunomodulators are being evaluated. Stress increases the intestinal permeability to large antigenic molecules. It can lead to mast cell activation, degranulation and colonic mucin depletion. A reversal of small bowel water and electrolyte absorption occurs in response to stress and is mediated cholinergically. Stress also leads to increased susceptibility to colonic inflammation, which can be adaptively transferred among rats by sensitized CD4(+) lymphocytes. The association between stress and various gastrointestinal diseases, including functional bowel disorders, inflammatory bowel disease, peptic ulcer disease and gastroesophageal reflux disease, is being actively investigated. Attention to the close relation between the brain and gut has opened many therapeutic avenues for the future.

Contraction induced by glicentin on smooth muscle cells from the human colon is abolished by exendin (9–39)

Glicentin and glucagon-like peptide-1 (7-36) amide (GLP-1) are gut hormones released during digestion. Glicentin and GLP-1 slow down gastric emptying and glicentin can switch off the duodenojejunal fed motor pattern. The effect of glicentin on the motor activity of colon has never been reported in humans. Our aim was to determine if circular smooth muscle cells (SMC) from the human colon are target cells for glicentin or GLP-1, and if their motility is dependent upon these digestive hormones. Twenty-two resections were performed on patients operated for colon adenocarcinoma. The SMC were isolated from colonic circular muscle layer and cell contraction was assessed. Glicentin caused a dose-related contraction of SMC, when GLP-1 determined a contraction of weak amplitude. Exendin-(9-39), described as a GLP-1 receptor antagonist, inhibited contraction due to glicentin or GLP-1. In contrast, on antral SMC from rabbit, GLP-1 exerts neither relaxation nor contraction; however, exendin-(9-39) dose dependently reduced the contractile activity of glicentin [glicentin EC(50) = 5 pM, exendin-(9-39) pA(2) = -9.36]. The circular muscle from the human colon is a target tissue for glicentin and GLP-1. Whereas glicentin is a long-life digestive hormone which would contribute to segmental contraction, the biological activity of GLP-1 remains unknown on this tissue. On the digestive smooth muscle, exendin-(9-39) behaved as an antagonist for two members of the glucagon-receptor family, GLP-1 and glicentin.

Normal aspects of colorectal motility and abnormalities in slow transit constipation

Human colonic motility is a relatively difficult topic to investigate. However, the refinement of manometric techniques in recent years enabled us to study both the proximal and distal segments of the viscus. The present paper reviews our knowledge about normal aspects of colorectal motility in man and the abnormalities found in slow transit constipation (STC), one of the most frequent and difficult to treat subtypes of constipation. An internet-based search strategy of the Medline and Science Citation Index was performed using the keywords colon, colonic, colorectal, constipation, slow transit, motility, rectal, rectum in various combinations with the Boolean operators AND, OR and NOT. Only articles related to human studies were used, and manual cross-referencing was also performed. Most of colonic motor activity is represented by single nonpropagated contractions, rarely organized in bursts; this activity is maximal during the day, especially after waking and following meals. In addition, a specialized propagated activity with propulsive features is detectable, represented by high- and low-amplitude propagated contractions. In the severe form of constipation represented by the slow transit type, the above motor activity is completely deranged. In fact, both basal segmental activity (especially in response to meals) and propagated activity (especially that of high amplitude) are usually decreased, and this may represent a physiologic marker of this disorder. Human colonic motor activity is quite a complex issue, still only partly understood and investigated, due to anatomic and physiological difficulties. In recent years, however, some more data have been obtained, even in proximal segments. These data have helped in elucidating, although only in part, some pathophysiological mechanisms of chronic constipation, and especially of the STC subtype.

Identification of the location of the colonic pacemakers: a histologic study

A recent electrophysiologic study has suggested the existence of 4 pacemakers in the colon which generate the electric waves that are responsible for the colonic motor activity. These pacemakers are located at the cecal pole, the cecocolonic junction, the mid third of the transverse colon and at the colosigmoid junction. We investigated the hypothesis that these pacemaker sites contain ICCs in great numbers and that the electric waves generated from these sites are transmitted by a chain of ICCs to the remaining colon. Specimens were taken from the 4 electrophysiologically defined pacemaker sites and the remaining colon of 24 cadavers. They were subjected to c-kit immunohistochemistry tests. Controls for antisera specificity consisted of tissue incubation with normal rabbit serum substituted for the primary antiserum. The morphometric study was performed by submitting the immunohistochemically-stained sections to image analysis in order to determine the area percent of immuno-reactivity in comparison to the total area of fields examined in the sections. Data obtained from the image analyzer were statistically analyzed. Immunohistochemical and morphometric studies have shown that the 4 electrophysiologically defined pacemaker sites contained a significantly higher proportion of ICCs than the remaining colon, the ICCs at these sites being multipolar and forming a network surrounded by a fibrous tissue wall. In the remaining colon, the ICCs were bipolar and arranged in a linear fashion. The study revealed the existence of a network of ICCs at the 4 pacemaker sites forming the 'pacemaker nodes' (PMNs). In the rest of the colon, a chain of ICCs extended in the colonic wall in a linear fashion forming the 'pacemaker bundles' (PMBs). We postulate that the colonic electric waves start at the PMNs and spread in the colon along the PMBs.

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.

Difficulty with evacuation after spinal cord injury: colonic motility during sleep and effects of abdominal wall stimulation.

Difficulty with evacuation (DWE) is common in individuals with spinal cord injury (SCI). Numerous studies have concluded that constipation, impaction, and incontinence cause significant morbidity and, collectively, constitute an important quality-of-life issue in individuals with SCI. Colonic motor activity was assessed using a solid-state manometry probe. We report here that colonic pressure activity is depressed during sleep compared to that observed in able-bodied controls. In addition, pressure activity was decreased during sleep compared to pre-sleep and post-sleep. We suspect that this may contribute to delayed colon transit time after SCI. In addition, since contraction of the abdominal wall musculature plays a role in normal defecation, we assessed whether an abdominal belt with implanted electrodes would improve DWE. In this respect, we demonstrated that neuromuscular stimulation of the abdominal wall improves a number of indices of defecatory function, including time to first stool and total bowel care time.

Electric activity of the colon in subjects with constipation due to total colonic inertia: an electrophysiologic study.

Idiopathic constipation may result from colonic inertia, which affects the whole colon or is localized to an area of the colon. The colon exhibits electric activity in the form of slow waves or pacesetter potentials (PPs) and action potentials (APs), which are coupled with elevated colonic pressure. The APs are claimed to be responsible for colonic motor activity. Colonic electric activity is disordered in patients with constipation due to colonic inertia. Electric activity was studied in 11 patients with colonic inertia and constipation (mean +/- SD age, 42.8 +/- 6.6 years; 7 women) who underwent total colectomy. Eight volunteers who had no gastrointestinal complaints (mean +/- SD age, 40.6 +/- 5.8 years; 5 women) acted as controls. Control subjects underwent laparotomy for hernia repair (n = 7 patients) and for removal of a mesenteric cyst (n = 1 patient). During the operation, 2 monopolar silver-silver chloride electrodes were applied to the cecum and the ascending, transverse, descending, and sigmoid colon. Electric waves (PPs and APs) were recorded from all parts of the colon in control subjects. The waves were monophasic, negatively deflected, and had regular rhythm. The wave variables from the 2 electrodes of each segment of the colon were identical and reproducible. They progressively increased aborally. In the colonic inertia group, 5 patients had recorded waves from the cecum and ascending colon but no waves from the rest of the colon. The wave variables were significantly lower than those of the controls (P =.02). In the remaining 6 patients, no waves were registered from the whole colon. Regular electric waves were recorded from the colons of control subjects. The aboral increase of their frequency, amplitude, and conduction velocity suggests that colonic motile activity increases analward, reaching its maximum in the sigmoid colon to expel its solid contents. We postulate that constipation in patients with colonic inertia is attributable to weak or absent electric activity, the cause of which is unknown. A disorder of the interstitial cells of Cajal, which generate electric activity, is suggested to have a role in inducing diminished or absent colonic motor activity, a point that should be investigated.

Electrophysiologic Identification of the Location of the Colonic Pacemakers in Humans: Further Study

We recently defined the sites of four colonic pacemakers that appear to generate the electric waves assumed to be responsible for the colonic motility. We hypothesized that a dysfunction of one or more of these pacemakers might interfere with the generation of electric waves and the colonic motility. This hypothesis was investigated in the current communication. The tests were performed during the repair of huge incisional hernia of 8 subjects (5 F, 3 M; mean age 42.8 +/- 3.3 SD years). Two electrodes were applied to each of the terminal ileum (TI), cecum (C), and ascending (AC), transverse (TC), descending (DC), and sigmoid (SC) colon. The electric activity of the TI and the various colonic segments was recorded using surface silver-silver chloride electrodes applied to the colon. The site of change of the wave variables between the TI and the C and between the different other colonic segments was determined by changing the position of the electrodes placed over the segments to be examined. Presumably, the sites where the wave variables changed represent the potential location of the pacemakers. We anesthetized these sites individually by injection of 2% Xylocaine, and then recorded the electric activity after 20 min in all the subjects and after 2 h in only 5 subjects. Electric waves in the form of pacesetter and action potentials were recorded from the TI and the colon. The sites of potential pacemakers could be defined at the ileocecal and cecocolonic junctions, at the mid third of the TC, and at the colosigmoid junction. Anesthetization of the cecal pole resulted in disappearance of the cecal electric waves, with persistence of the waves from the other colon segments. Anesthetization of the cecocolonic junction eliminated the electric waves of the AC and the right half of the TC, while the waves in the rest of the colon persisted. The remaining two pacemaker sites produced similar results when anesthetized. The electric waves reappeared after the anesthetic effect had waned. Thus, the colon possesses at least four pacemakers that appear to mediate the colonic motor activity. Individual pacemaker block by anesthetization effected disappearance of electric waves in the relative colonic segment, which reappeared after waning of the anesthetic effect. The disappearance of these waves upon pacemaker anesthetization supports a relationship between the pacemakers at the anesthetized site and the electric waves. The electric waves seem to be generated by these pacemakers. We suggest that colonic inertia, segmental or total, results from the dysfunction of one or more pacemakers, and that an artificial pacemaker could be applied for the treatment of such conditions. These suggestions need to be further studied.

Are colonic regular contractile frequency patterns in slow transit constipation a relevant pathophysiological phenomenon?

Pathogenesis of slow transit constipation still remains elusive. Some studies have shown several colonic motor abnormalities; however, it is not easy to understand the relative importance of the single ones. Since it has been hypothesized that an excess of periodic distal motor activity may be of pathophysiological importance in patients with slow transit constipation, we evaluated regular colonic contractile frequencies in a homogeneous cohort of these patients. A total of 26 female patients (age range 34 to 67 years) fulfilling the Rome II criteria for constipation entered the study. No patient had evidence of secondary forms of constipation and distal obstruction. Twenty-four hour colonic manometric studies were obtained for each patient. Regular contractile patterns (with frequencies ranging from 2 to 8 cycles/min) were calculated for the entire recording period and in single colonic segments. Overall, regular patterns accounted for about 3% of the total colonic motor activity (average 30 min/day per subject), with the 3 cycles/min being the predominant contractile rhythm. Most of this activity was present in the sigmoid colon, accounting for >50% of the total amount of motility, and it was more prevalent than in the descending and transverse colon; no differences were revealed in the descending with respect to the transverse colon. No daily fluctuations of regular contractile activity, nor a cyclic pattern, nor migration between recording points were observed. Regular colonic frequency patterns are probably of minor pathophysiological importance in slow transit constipation, even in the light of the scant amount of such phenomena previously documented in healthy subjects.

Stimulatory action of itopride hydrochloride on colonic motor activity in vitro and in vivo.

We investigated the effects of itopride hydrochloride (itopride, N-[4-[2-(dimethylamino)ethoxy]benzyl]-3,4-dimethoxybenzamide hydrochloride), a gastroprokinetic agent, on the colonic motor activity in vitro and in vivo, in comparison with benzamides, cisapride hydrate (cisapride), and mosapride citrate (mosapride). Itopride stimulated both peristaltic and segmental motility induced by applying intraluminal pressure to the isolated guinea pig colon. Although cisapride and mosapride enhanced the segmental motility, they markedly reduced the peristaltic motility. In conscious dogs with implanted strain gauge force transducers, itopride stimulated contractile activity in the gastrointestinal tract from the stomach to the colon. Cisapride stimulated contractile activity in the gastric antrum, ileum, and ascending colon. Mosapride stimulated contractile activity only in the gastric antrum and ileum. In guinea pigs and rats, itopride accelerated colonic luminal transit. On the other hand, cisapride and mosapride failed to enhance colonic transit. These results demonstrate that itopride has a stimulatory action on colonic peristalsis, propelling colonic luminal contents, different from that of cisapride and mosapride. Therefore, itopride may be a useful drug for the treatment of functional bowel disorders such as functional constipation.

Electrophysiologic Identification of the Location of the Colonic Pacemakers in Humans: Further Study

We recently defined the sites of four colonic pacemakers that appear to generate the electric waves assumed to be responsible for the colonic motility. We hypothesized that a dysfunction of one or more of these pacemakers might interfere with the generation of electric waves and the colonic motility. This hypothesis was investigated in the current communication. The tests were performed during the repair of huge incisional hernia of 8 subjects (5 F, 3 M; mean age 42.8 - 3.3 SD years). Two electrodes were applied to each of the terminal ileum (TI), cecum (C), and ascending (AC), transverse (TC), descending (DC), and sigmoid (SC) colon. The electric activity of the TI and the various colonic segments was recorded using surface silver-silver chloride electrodes applied to the colon. The site of change of the wave variables between the TI and the C and between the different other colonic segments was determined by changing the position of the electrodes placed over the segments to be examined. Presumably, the sites where the wave variables changed represent the potential location of the pacemakers. We anesthetized these sites individually by injection of 2% Xylocaine, and then recorded the electric activity after 20 min in all the subjects and after 2 h in only 5 subjects. Electric waves in the form of pacesetter and action potentials were recorded from the TI and the colon. The sites of potential pacemakers could be defined at the ileocecal and cecocolonic junctions, at the mid third of the TC, and at the colosigmoid junction. Anesthetization of the cecal pole resulted in disappearance of the cecal electric waves, with persistence of the waves from the other colon segments. Anesthetization of the cecocolonic junction eliminated the electric waves of the AC and the right half of the TC, while the waves in the rest of the colon persisted. The remaining two pacemaker sites produced similar results when anesthetized. The electric waves reappeared after the anesthetic effect had waned. Thus, the colon possesses at least four pacemakers that appear to mediate the colonic motor activity. Individual pacemaker block by anesthetization effected disappearance of electric waves in the relative colonic segment, which reappeared after waning of the anesthetic effect. The disappearance of these waves upon pacemaker anesthetization supports a relationship between the pacemakers at the anesthetized site and the electric waves. The electric waves seem to be generated by these pacemakers. We suggest that colonic inertia, segmental or total, results from the dysfunction of one or more pacemakers, and that an artificial pacemaker could be applied for the treatment of such conditions. These suggestions need to be further studied.