Sigmoid Motility Research Articles

Colonic smooth muscle cells and colonic motility patterns as a target for irritable bowel syndrome therapy: mechanisms of action of otilonium bromide.

Otilonium bromide (OB) is a spasmolytic compound of the family of quaternary ammonium derivatives and has been successfully used in the treatment of patients with irritable bowel syndrome (IBS) due to its specific pharmacodynamic effects on motility patterns in the human colon and the contractility of colonic smooth muscle cells. This article examines how. OB inhibits the main patterns of human sigmoid motility in vitro, which are spontaneous rhythmic phasic contractions, smooth muscle tone, contractions induced by stimulation of excitatory motor neurons and contractions induced by direct effect of excitatory neurotransmitters. It does this mainly by blocking calcium influx through L-type calcium channels and interfering with mobilization of cellular calcium required for smooth muscle contraction, thereby limiting excessive intestinal contractility and abdominal cramping. OB also inhibits T-type calcium channels and muscarinic responses. Finally, OB inhibits tachykinin receptors on smooth muscle and primary afferent neurons which may have the joint effect of reducing motility and abdominal pain. All these mechanisms mediate the therapeutic effects of OB in patients with IBS and might be useful in patients with other spastic colonic motility disorders such as diverticular disease.

Effect of otilonium bromide on contractile patterns in the human sigmoid colon

The mechanism of action of the spasmolytic compound otilonium bromide (OB) on human colonic motility is not understood. The aim of our study was to characterize the pharmacological effects of OB on contractile patterns in the human sigmoid colon. Circular sigmoid strips were studied in organ baths. Isolated smooth muscle cells from human sigmoid colon were examined using the calcium imaging technique. Otilonium bromide inhibited by 85% spontaneous non-neural rhythmic phasic contractions (RPCs), (IC(50) = 49.9 nmol L(-1)) and stretch-induced tone (IC(50) = 10.7 nmol L(-1)) with maximum effects at micromolar range. OB also inhibited by 50% both on- (IC(50) = 38.0 nmol L(-1)) and off-contractions induced by electrical stimulation of excitatory motor neurons. In contrast, the inhibitory latency period prior to off-contractions was unaffected by OB. OB inhibited acetylcholine-, substance P-, and neurokinin A-induced contractions. The L-type Ca(2+) channel agonist BayK8644 reversed the effects of OB on RPCs, on- and off-contractions. Hexamethonium, atropine, the NK(2) antagonist, or depletion of intracellular Ca(2+) stores by thapsigargin did not prevent the inhibitory effect of OB on RPCs and electrical contractions. KCl-induced calcium transients in isolated smooth muscle cells were also inhibited by OB (IC(50) = 0.2 micromol L(-1)). Otilonium bromide strongly inhibited the main patterns of human sigmoid motility in vitro by blocking calcium influx through L-type calcium channels on smooth muscle cells. This pharmacological profile may mediate the clinically observed effects of the drug in patients with irritable bowel syndrome.

Abnormalities of colonic function in patients with rectal prolapse and faecal incontinence.

We have investigated changes in colonic motility and anorectal function in 6 continent patients with a rectal prolapse; in 10 incontinent patients with rectal prolapse and in 16 patients with idiopathic faecal incontinence compared with 26 age and sex match controls. A history of incontinence, irrespective of a prolapse, was associated with significantly lower anal squeeze pressures (P less than 0.05), a deficient anorectal angle (P less than 0.05), failure to retain a balloon containing more than 250 cm3 of air in the rectum (P less than 0.01) and increased sigmoid motility (P less than 0.02) compared with controls. By contrast patients with rectal prolapse and no incontinence had normal anal pressures, a normal anorectal angle and normal sigmoid motility, but transit was delayed. These results indicate that abnormal sigmoid motility is commonly associated with faecal incontinence and that slow transit constipation is frequent in patients with rectal prolapse who are continent.

Sigmoid motility and clinical results after transverse taeniamyotomy for diverticular disease.

Abstract The purpose of our investigation was to evaluate the effect of multiple transverse taeniamyotomy on sigmoid motility and on the clinical picture of 8 patients affected by symptomatic, uncomplicated diverticular disease of the sigmoid, selected for the operation after the failure of medical therapy. We recorded rectosigmoid intraluminal pressures and the manometric tracings were correlated with the corresponding photofluorograms before and after the operation for 1 year. Motility indices were computed and a significant decrease after meals and Prostigmin was found in patients who underwent transverse taeniamyotomy. These functional changes were accompanied by a marked clinical recovery, expressed in terms of relief from lower abdominal pain and improvement in bowel movements. Considering the functional and clinical disadvantages reported after colectomy and longitudinal myotomy, and observing our results after transverse taeniamyotomy, even though they are short term results, we conclude that the latter operation is an effective procedure for the treatment of diverticular disease with muscular hypertrophy and high intracolonic pressure which has not responded to a medical and dietetic regimen.

Colon Motility in Opiate Addiction and Naloxone‐Precipitated Withdrawal

More than half of those who use opiates suffer from constipation, and withdrawal from opiates produces abdominal cramps and diarrhea in 70% to 85%. These withdrawal symptoms may influence the number of opioid‐dependent patients who attempt abstinence and the number who relapse. To characterize the motility correlates of these gastrointestinal symptoms of withdrawal, six patients from a drug treatment program were studied while on maintenance doses of methadone (average of 57.5 mg/d) and during acute naloxone‐precipitated withdrawal. Motility was recorded via open‐tipped catheters at 30 cm and 15 cm from the anal verge during a 15‐minute baseline period and for 15 minutes during mechanical distention of the rectosigmoid colon with a balloon. This sequence was repeated during withdrawal. Subjective symptoms and objective signs of withdrawal assessed at 15‐minute intervals showed that all six patients experienced withdrawal. Sigmoid and rectal motility were also assessed in 18 opiate‐free control subjects. Long‐term methadone use was associated with normal sigmoid and rectal motility under baseline conditions, but methadone users did not show the inhibition in sigmoid motility that normal subjects exhibited following baloon distention. When withdrawal was precipitated by naloxone, methadone users showed significant increases in rectosigmoid motility in association with signs and symptoms of withdrawal.

Sigmoid motility in diverticular disease and the irritable bowel syndrome.

Intraluminal pressures were measured with four open ended, water perfused tubes in the fasting state and after a standard liquid meal (400 KCal, 375 ml, protein 15 g, carbohydrate 55 g, lipid 13.4 g) in six patients with sigmoid diverticular disease, 20 with the irritable bowel syndrome and in 13 controls. The pressure sensors were positioned in the true sigmoid colon at colonoscopy at 25, 35, 45, and 55 cm from the anus. Colonic pressures were significantly higher in diverticular disease than in controls before (p less than 0.02) and after the meal (p less than 0.002), some pressure amplitudes exceeding 300 cm H2O. Patients with the irritable bowel syndrome had lower (p less than 0.05) pressures than controls before the meal. Postprandial sigmoid pressures were within the mean +/- 2 SD of controls in 10, above in two and below in eight patients with the irritable bowel. Hypercontractility of the sigmoid colon in the irritable bowel syndrome was not confirmed under the conditions of this study. The association between sigmoid diverticulosis and high intraluminal pressures is confirmed.

Transverse and sigmoid colon motility in healthy humans: effects of eating and of cimetropium bromide.

There have been few studies of the motility of the colon proximal to the rectosigmoid area. For this purpose we evaluated (1) fasting and postprandial transverse and sigmoid colon motor activity and (2) the effects of a new nonselective anticholinergic drug, cimetropium bromide, on transverse and sigmoid motor responses to eating. Two paired studies were carried out in 11 healthy volunteers by means of a colonscopically positioned manometric probe. After placebo, eating significantly increased transverse and sigmoid motility indices throughout the recording period. Cimetropium significantly reduced the motor responses to eating in both the transverse and the sigmoid colon.

Physiologic study of the terminal digestive tract in chronic painful constipation.

A manometric study of the sigmoid colon and of the anorectum was undertaken in 65 chronically constipated patients complaining of abdominal pain, and in a control group of 23 healthy volunteers. Rectal compliance was tested in both groups. The sigmoid motility study allowed for the segregation of the constipated patients into three groups: hypokinesia (12 cases), normokinesia (34 cases), hyperkinesia (19 cases). Rectal manometry showed anal hypertony in 24 patients, impaired rectal conscious sensitivity in 12 subjects, and normal functions in the remaining cases. The rectal compliance study disclosed a decreased compliance in 15 cases and increased compliance in 13 other patients. In 12 cases disordered sigmoid motility was the only abnormality; in 10 cases only a rectoanal abnormality was found. Most of the patients (52%) exhibited miscellaneous disorders. In contrast, all parameters were normal in nine subjects. No consistent pattern of motility disorders was thus demonstrated in this clinically homogeneous group of patients with chronic, painful, constipation.

Changes in colorectal function in severe idiopathic chronic constipation

Physiologic studies of colorectal and anal function were performed in 25 adult patients with severe idiopathic long-standing constipation compared with 22 age- and sex-matched normal subjects. Only patients with primary severe idiopathic constipation with no known underlying primary etiology have been studied. No significant changes were observed in the resting or squeeze anal canal pressures. There was indirect evidence that rectal sensation was grossly impaired in 17 of the constipated patients: mean values for constant sensation compared with controls being 269 ± 21 ml and 136 ± 10.3 ml, respectively (p < 0.01). The mean anorectal angles during attempted defecation were significantly less in constipated patients compared with controls (p < 0.001), and 10 patients were unable to evacuate from the rectum a balloon containing 150 ml of a weak barium suspension. Electromyography of the pelvic floor showed increased puborectalis activity on attempted defecation in 9 subjects. Although there was no significant difference in the basal sigmoid motility index between constipated patients and controls, response to intrarectal bisacodyl (5 mg) was impaired in the constipated group, being 479 ± 22.1 and 735 ± 24.7, respectively (p < 0.01). Transit time was significantly delayed in the constipated patients; the percentage of markers passed by constipated patients after 5 days was 39.0 ± 6.9 compared with 73.9 ± 2.8 passed by controls (p < 0.02). These results imply that there is often a motor abnormality of the pelvic floor and the colon in patients with long-standing chronic constipation.

Sigmoid motility in constipation

Sigmoid motility in constipation

A controlled double-blind study of sigmoid motility using psyllium mucilloid in diverticular disease (DD)

A controlled double-blind study of sigmoid motility using psyllium mucilloid in diverticular disease (DD)

Motor effect of dopamine on human sigmoid colon. Evidence for specific receptors.

The effect of dopamine on human sigmoid motility has been studied in 26 subjects. To record mechanical activity of the sigmoid colon, two small, air-filled balloons mounted on a probe introduced through a sigmoidoscope were used. The recordings were made at a distance of 25 and 15 cm from the anal edge. Dopamine was infused for 10 min after a 30-min control infusion of physiologic solution. Mean amplitude, mean duration, mean frequency, percentage of motor activity, and motility index of the pressure waves were determined. The motor response to dopamine was characterized by an increased baseline pressure with phasic waves superimposed. Dopamine produced a significant response at the dose of 5 microgram/kg/min. Alpha and beta antagonizing agents failed to oppose the effect of dopamine, while anticholinergic drugs enhanced its motor action. These studies suggest that dopamine may stimulate the motor function of human large bowel through specific receptors.

The effect of intravenous prostaglandin F2 alpha and E2 on the motility of the sigmoid colon.

The effect of a 20-min intravenous infusion of prostaglandin E2 (0-08 mug kg-1 min-1) or of prostaglandin F2 alpha (0-8 mug kg-1 min-1) on the segmental pressures in the sigmoid colon was studied in 12 patients. Prostaglandin F2 alpha had no measurable effect, but prostaglandin E2 significantly inhibited sigmoid motility.

Intestinal motility in man: the effect of bradykinin on the motility of the distal colon.

The effect of intravenously administered bradykinin on sigmoid motility was studied in subjects with normal and disordered bowel habits. The administration of bradykinin generally reduced the motility in normal subjects as well as in patients with organic and functional conditions. The response, however, was sometimes variable. The greatest reduction was observed in patients with diarrhea. The motor activity induced by prostigmine was abolished by bradykinin. In the control group, the over-all responses were more variable, for reasons which are not understood.

Comparative Potency of Newer Anticholinergic Drugs in Man: As Determined by Sigmoid Motility Technique

Comparative Potency of Newer Anticholinergic Drugs in Man: As Determined by Sigmoid Motility Technique

Effects of certain antispasmodic drugs on the intact human colon, with special reference to banthine (β-diethylaminoethyl xanthene-9-carboxylate methobromide)

A simple method for the study of colonic motility in intact human beings is described. By this method orally administered atropine, trasentine and syntropan were found to be without significant or sustained effect on sigmoid motility. The inability of these drugs to inhibit motor activity of the sigmoid may be related to their failure in treatment of functional disorders of the colon. In thirty-seven individuals a new quaternary amine, banthine (beta-diethyl-aminoethyl xanthene-9-carboxylate methobromide), profoundly depressed sigmoid motility. Although the data accumulated by this method are not complete, this agent appears to be much more potent than other clinically acceptable antispasmodic drugs.

Experimental studies on the irritable colon

When under stress induced by experimental stimuli, both healthy persons and patients with irritable colon may show disturbances in motility and engorgement of the sigmoid colon coincident with periods of emotional tension. Two patterns of altered sigmoid motility have been recognized: the one an increase in tone and/or wave-like contractions associated with overt moods of hostility and aggression; the other a decrease in tone and/or contractions associated with overt behavior symbolizing hopelessness and defeat. A possible relationship of these patterns to the mechanisms of spastic constipation and functional diarrhea is discussed.

Alterations in Colonic Function in Man Under Stress

Summary In 18 patients with irritable colon undergoing kymographic studies of sigmoid motility, a sudden and marked reduction in tone and wavelike motility occurred for periods of 1 to 37 minutes. This pattern was associated with a change in the mood of the subject to one of personal inadequacy, self-reproach, and hopelessness. On 11 occasions in 6 subjects, the pattern coincided exactly with periods of weeping. In one instance studied with tandem balloons, the pattern was observed only in the distal segment. Clinical and experimental evidence is presented, suggesting a link between this phenomenon and the bodily mechanism of diarrhea.