Effects of trimebutine on colonic function in patients with chronic idiopathic constipation: evidence for the need of a physiologic rather than clinical selection.

A double-blind crossover study on the effects of trimebutine on large bowel function was performed in 24 consecutive patients complaining of chronic idiopathic constipation. Their stool frequency, colonic transit time, and colonic electrical activity were measured. They were divided into a group of constipated patients with "normal" transit time (less than 40 hours) (n = 12) and another group of constipated patients with "delayed" transit time (more than 40 hours) (n = 12). The patients received trimebutine (200 mg/day per os) for one month and a placebo for another month, at random, with a washout period in between. Results show that stool frequency increased (P < 0.001) in all patients as soon as they entered the study; there was no difference between trimebutine and placebo. Colonic transit time was significantly reduced (P < 0.05) with trimebutine in patients with delayed transit time (from 105 +/- 19 hours to 60 +/- 11 hours; mean +/- SE), while it did not change with placebo (from 103 +/- 17 hours to 95 +/- 10 hours). It was slightly but not significantly increased in patients with normal transit time following trimebutine therapy. Electrical activity was not influenced by trimebutine or placebo in constipated patients with normal transit time, either before or after a meal. The number of propagating bursts during the postprandial period was significantly (P < 0.05) increased in patients with delayed transit (from 2.1 +/- 0.3 bursts/hour to 3.5 +/- 0.6 bursts/hour after trimebutine); it was decreased but not significantly with placebo (from 2.6 +/- 0.8 bursts/hour to 1.6 +/- 0.6 bursts/hour) in the same group of patients. Thus, stool frequency in patients with chronic idiopathic constipation was influenced mainly by a placebo effect. Colonic transit time was reduced by trimebutine, but this was found only in patients with delayed colonic transit; myoelectric propagating bursts were increased, and this probably explains the improvement. In conclusion, trimebutine may be of value in the treatment of patients with chronic idiopathic constipation, provided that a careful pathophysiologic evaluation reveals that they have a colonic transit time that exceeds the normal range. In addition, this study provides some argument for selecting patients with functional motor disorders of the large intestine to be entered into a research protocol or to be treated not on the basis of what they complain about--the symptom--but on the basis of some kind of measurement of dysfunction--a corresponding sign.

Idiopathic constipation by colonic dysfunction. Relationship with personality and anxiety.

The personality of two groups of constipated women (by delayed colonic transit or by colonic inertia) was compared to that of two control groups of arthritic patients (rheumatoid or degenerative disease) with the Minnesota Multiphasic Personality Inventory (MMPI). All subjects suffered from chronic pain. Constipated women were found to have significantly higher scores on the hypochondria, hysteria, control, and low back pain scales and a lower score on the masculinity-femininity scale. Discriminant analysis permitted us to sort out constipated from arthritic patients in 83% of the cases, on the basis of only the personality data. In women with constipation by delayed colonic transit, multiple regression analysis demonstrated a close link (r = 0.90; P less than 0.001) between transit time in the ascending colon and levels of anxiety. It is concluded that women with constipation of colonic origin have a different pattern of personality than arthritic women and that severe constipation may play the role of a defense mechanism, where psychophysiologic responses to life stresses replace normal emotional reactions.

[Vasopressin and colonic motility]. / Vasopressine et motilité colique.

Vasopressin (VS) has been reported to stimulate colonic peristalsis in different therapeutic conditions. In order to determine the mechanisms involved in this effect, colonic function was studied with three different techniques staying: a) the transit time of radioopaque markers through the colon was measured in 7 healthy subjects after VS IM (0.3 U/kg of weight). A marked propulsive effect was observed. One hour after injection, 64.7 +/- 16.2 p. 100 of the markers (m +/- sem) had left the right colon vs 9.1 +/- 4.6 p. 100 after injection of NaCl (p less than 0.01) and 70.5 +/- 10.8 p. 100 of the markers emptied from the left colon vs 4.3 +/- 4.5 p. 100 after NaCl (p less than 0.01); b) an electromyographic study was carried out in 6 other healthy subjects with an intraluminal device equipped with contact electrodes, introduced into the left colon by colonoscopy. The injection of VS was followed by an increase in the number of the propagating electrical spike bursts that are known to correlate well with the propulsion of the colonic intraluminal contents. The number of bursts was 2.7 +/- 0.6 bursts/30 min after NaCl and 5.2 +/- 1.4 bursts/30 min after VS (p less than 0.02); c) finally, the outflow of ileostomies and colostomies was measured in respectively 3 and 8 subjects over one h after IM 0.3 U/kg of VS. A considerable increase in the outflow of intestinal fluids was observed: output from the colostomies was 10 +/- 10 ml/h after NaCl and 250 +/- 39 ml/h after VS (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Megarectum.

Evaluation of the rectum by barium enema does not correlate well with rectometrographic studies and is not predictive of bowel function. The purpose of the present study was to describe clinical and functional data in patients with chronic idiopathic constipation, where a megarectum was diagnosed by a rectometrogram. Among 355 patients who underwent rectal elasticity studies, 35 were found to have a megarectum (maximum tolerable volume above 320 ml in women and 440 in men) for which no specific etiology was recognized. They, and a group of 11 healthy controls who were not sensitive to stress, underwent studies of stool frequency, colonic transit time of radiopaque markers, rectal elasticity, and anorectal pressures and reflexes. The elasticity coefficient of the rectal wall was decreased in patients as compared to controls (P less than 0.01). Seven patients had onset of symptoms at birth, with maximum tolerable volume in the rectum between 460 and 900 ml, and all were incontinent for feces. Studies of colonic transit times demonstrated normal function in the right and left colon, but there was rectosigmoid stagnation (transit time of 122 +/- 17 hr vs 8 +/- 2 in stress-free controls; X +/- SE; P less than 0.001). In the other 28 patients (late-onset megarectum), in contrast to the congenital group, there was a marked female preponderance, and their recorded stool frequency (4 +/- 0.7/week) was greater than the recalled frequency (1.4 +/- 0.2/week; P less than 0.001). Only half suffered from fecal incontinence. They did not have a greater rectal capacity when colonic transit times were prolonged (455 +/- 27 ml) than when normal (422 +/- 27). Rectal pressure was similar at the level of conscious sensation of filling, regardless of rectal capacity, suggesting a motor, rather than a sensory, abnormality. The amplitude of the rectoanal inhibitory reflex was decreased (P less than 0.001) as compared to controls, sometimes mimicking the findings of Hirschsprung's disease, but increasing rectal distension always induced a relaxation of the internal anal sphincter. The notion of a megarectum, which tolerates large amounts of fluid without sensation, lacks elasticity, and is accompanied by an abnormal rectoanal inhibitory reflex, provides an explanation for one of the mechanisms of constipation by outlet obstruction.

Effects of rest, stress, and food on myoelectric spiking activity of left and sigmoid colon in humans.

The great variability which is known to affect colonic motility may partly be the result of changes in physiological conditions. In order to test this hypothesis, 40 subjects were sequentially put in conditions of vigilance, rest, stress, and feeding while colonic motility was monitored. The myoelectric spiking activity of the left colon was recorded with a 50-cm-long silastic tube equipped with four bipolar ring electrodes (located 10 cm apart) introduced into the left colon by flexible sigmoidoscopy. Tracings were performed while the subjects were kept awake (by conversation) for 1 hr, put at rest (quiet) for another 1 hr, submitted to a stress (by alternatively immersing and removing one hand from 2-4 degrees C cold water) for 20 min, and finally recorded for 2 hr after a 800-kcal meal. In 18 other subjects, the sequences of vigilance and rest were randomized. The results showed that colonic spiking activity was made of sporadic bursts that are known to be associated with intraluminal propulsion and of stationary bursts that probably play no role in colonic peristalsis. The duration of sporadic spiking activity was respectively 13.6 +/- 1.2 min/hr (mean +/- SEM) during the period of vigilance, 5.4 +/- 0.6 min/hr during the period of rest (P less than 0.001), 14.3 +/- 1.0 min/hr during the period of stress (NS), and 16.8 +/- 1.2 min/hr after a meal (P less than 0.05). The duration of stationary spiking activity did not change significantly throughout the four periods, respectively, 6.6 +/- 4.9, 4.4 +/- 3.7 (NS), 5.2 +/- 3.9 (NS), and 3.3 +/- 2.8 min/hr (NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Stimulation of colonic peristalsis by vasopressin: electromyographic study in normal subjects and patients with chronic idiopathic constipation.

The effects of vasopressin on colonic motility were investigated in 6 healthy subjects and 10 patients with chronic idiopathic constipation. Recordings of the colonic myoelectric spiking activity were performed by means of 50-cm long silastic tube, equipped with four bipolar ring electrodes fixed at 10-cm intervals, which was introduced by flexible colonoscopy into the left colon. Tracing were obtained for 1 h in the fasting state and for another hour after an intramuscular injection of a pharmacological dose of vasopressin (0.3 U/kg). The different types of spike bursts generated by the colonic smooth muscle were compared before and after vasopressin injection. In both controls and patients, the tracing showed (i) rhythmic stationary spike bursts (RSB) that were seen at only one electrode site; and (ii) sporadic bursts that were either propagating over all four electrodes (SPB) or nonpropagating (SNPB). Injection of vasopressin in controls was followed for 30 min by a significant increase in the number of propagating bursts from 2.7 +/- 0.6 (mean +/- SEM) to 5.2 +/- 1.4 bursts (p less than 0.05); RSB and SNPB were not altered by vasopressin. In the constipated patients, the number of propagating bursts during the control period was significantly lower (0.8 +/- 0.2 bursts/30 min) than in the volunteers (p less than 0.05). After vasopressin, there was a significant increase to 3.6 +/- 0.8 bursts/30 min (p less than 0.001); RSB and SNPB also did not show significant alteration after vasopressin. Finally, 4 out of the 10 patients passed stools during the recording session.(ABSTRACT TRUNCATED AT 250 WORDS)

Myoelectrical activity and intraluminal flow in human sigmoid colon.

Myoelectric spike bursts were recorded in the sigmoid colon by means of an intraluminal silastic tube equipped with 3 Ag-AgCl ring electrodes fixed 15 cm apart on the tube that was introduced by flexible sigmoidoscopy. In six subjects, the tube was also equipped with three catheters whose tip opened 1 cm aborad from each electrode, for pressure recordings. In six other subjects, the tube was equipped with both electrodes and a catheter opening at the tip of the probe for infusing fluids at a rate of 12 ml/min into the colonic lumen. The fluid was collected with another tube inserted in the rectum and the volume was measured at 1-min intervals. Colonic spiking activity was made of rhythmic stationary bursts (RSB) and of sporadic bursts that were either propagating (SPB) or not propagating (SNPB). All sporadic bursts were associated with intraluminal pressure waves whose amplitude was significantly higher than that associated with rhythmic bursts. In the infusion experiments, the volume of fluid collected did not change significantly whether rhythmic bursts were present or not (3.9 +/- 1.7 ml/min and 3.3 +/- 1.9 ml/min respectively) (mean +/- SD). However, the volume was significantly higher when sporadic nonpropagating bursts were present (9.4 +/- 4.1 ml/min), and even higher when the sporadic bursts were propagating (21.6 +/- 8.8 ml/min). These results indicate that the occurrence of sporadic bursts, particularly when propagating, is associated with intraluminal pressure waves that lead to significant propulsive movements; and rhythmic bursts do not seem to be involved in colonic propulsive activity.

Hindgut dysgenesis as a cause of constipation with delayed colonic transit.

In a patient complaining of constipation since birth, delayed transit time in the ascending colon was related to a congenital malformation of the hindgut, different from Hirschsprung's disease. This was associated with absence of the left lobe of the liver. There was no propagating electrical muscular activity in the distal bowel.

How does morphine work on colonic motility? An electromyographic study in the human left and sigmoid colon.

The effect of morphine on colonic motility was investigated by recording the colonic myoelectric spiking activity by means of a 50 cm long silastic tube equipped with 4 bipolar AgAgCl ring electrodes fixed at 10 cm intervals that was introduced into the left colon in 8 healthy subjects by flexible sigmoidoscopy. Tracings were obtained for 1 hour in the fasting state and for another 1 hour after i.m. injection of morphine sulphate 0.15 mg/kg. The different types of spike bursts were compared before and after morphine injection. The control tracings showed that the spiking activity of the colon was made of 2 types: 1)- Rhythmic Stationary Spike Bursts (RSB), that were seen at only one electrode site; 2)- Sporadic Bursts, that were either propagating over all 4 electrodes (SPB) or non propagating (SNPB). Injection of morphine was followed by 1)- a considerable increase in the number of RSB from 107 +/- 43 bursts/hour (mean +/- SEM) to 491 +/- 23 bursts/hour; 2)- the complete disappearance of the SPB dropping from 7.3 +/- 2.0 bursts/hour to 0.3 +/- 0.2 bursts/hour; 3)- no significant change in SNPB (from 52 +/- 4 bursts/hour to 57 +/- 5 bursts/hour). These results indicate that 1)- stimulation of colonic smooth muscle activity by morphine seems to result from an increase in the number of rhythmic stationary bursts; 2)- however inhibition of colonic transit may be related to the decrease in the number of sporadic propagating bursts.

Changes in colonic myoelectric spiking activity during stimulation by bisacodyl.

The purpose of this study was to determine some relationships between colonic myoelectric spiking activity and intraluminal propulsion when colonic peristalsis was stimulated by bisacodyl. Myoelectric recordings were obtained in 12 subjects by means of a 50 cm long Silastic tube equipped with four bipolar electrodes fixed at 10-cm intervals. The tube was introduced into the left colon by flexible sigmoidoscopy and the electrodes were located at 50, 40, 30, and 20 cm from the anal verge. A small polyethylene catheter opening at the proximal end of the Silastic tube was used for introducing the laxative into the colon. One hour recording sessions were obtained before and after bisacodyl administration (5 mL of 0.4% solution). The control tracings showed that colonic spiking activity was made of rhythmic stationary bursts that occurred at only one electrode site and of sporadic bursts that were either propagating over the whole colonic segment or nonpropagating. Administration of bisacodyl was followed by complete suppression of the rhythmic stationary activity; a considerable increase in the sporadic spiking activity, propagating as well as nonpropagating; the occurrence of abdominal cramps and urgency to defecate, both associated with the propagating sporadic spike bursts. It is concluded that colonic propulsion induced by bisacodyl may be dependent upon the production of the sporadic bursts, particularly the propagating ones, while the rhythmic stationary bursts do not seem to play a significant role in colonic transit.

Beneficial effects of naloxone in a patient with intestinal pseudoobstruction.

A 15-day course of Naloxone treatment was given to a patient with intestinal pseudoobstruction who had previously undergone subtotal colectomy with terminal ileostomy for invalidating constipation. The effects of the drug were assessed according to symptoms, by recording the myoelectric activity of the stomach, and by measuring gastric emptying of a radiolabeled solid-liquid meal and the intestinal transit time of radiopaque markers. All tests were performed 1) at baseline; 2) after 2 wk with Naloxone 1.6 mg subcutaneous per day; and 3) after 8 days of placebo. Results showed that before treatment gastric emptying of solids was delayed, emptying of liquids was normal, myoelectric activity of the stomach was normal, small intestinal transit time of radiopaque markers was considerably increased while ileal output was markedly decreased. After Naloxone, gastric emptying of solids was markedly accelerated, emptying of liquids remained normal, gastric electrical spiking activity increased, small intestinal transit time strikingly decreased, and ileal output increased. After placebo, a tendency to return to pretreatment values was observed. This observation suggests that Naloxone may be helpful in the treatment of some patients with intestinal pseudoobstruction.

[Constipation caused by colonic inertia and distal obstruction: electromyographic study]. / Constipation par inertie colique et obstruction distale: étude électromyographique.

Colonic motility was evaluated in 15 patients with chronic constipation and 12 healthy subjects by both measuring the transit time of 20 radiopaque markers and recording the colonic myoelectric signals by means of a silastic tube equipped with 4 ring contact electrodes. The tube was introduced by flexible sigmoidoscopy so as the electrodes be located at 50, 40, 30 and 20 cm from the anal verge. Constipation resulted from colonic inertia in 7 patients, the markers being delayed over the whole length of the colon. In the 8 other patients, constipation was due to distal obstruction, the markers accumulating electively in the rectum. The myoelectric tracings showed in the control subjects, on one hand rhythmical stationary spike potentials that occurred at only one electrode site at a mean rate of 10 per minute; on the other hand sporadic (non-rhythmic) spike potentials that were either propagating over the colonic segment (sporadic propagating potentials) or not (sporadic non-propagating potentials). In the constipated patients, the following changes were observed: 1) the number of sporadic propagating potentials was significantly decreased in colonic inertia (2.5 +/- 1.3 bursts of spikes per hour) compared to the controls (8.5 +/- 1.1 bursts/h) or distal obstruction (7.9 +/- 1.3 bursts/h); 2) sporadic propagating potentials usually moved aborally; however, 19.8 +/- 0.9 p. 100 moved orally in colonic obstruction, while 4.6 +/- 0.2 p. 100 in the controls and 4.7 +/- 0.1 p. 100 in colonic inertia.(ABSTRACT TRUNCATED AT 250 WORDS)

Fasting and postprandial myoelectric spiking activity in the human sigmoid colon.

The colonic myoelectric spiking activity was recorded in 10 healthy subjects using an intraluminal tube equipped with four bipolar Ag-AgCl ring electrodes fixed 10 cm apart. The probe was introduced into the sigmoid colon by endoscopy so as to place the electrodes at 50, 40, 30, and 20 cm, respectively, from the anal verge. Recordings were performed for 2 h in the fasting state and for an additional 2 h after an 800-kcal mixed meal. The tracings showed two patterns of spiking activity. One was made of rhythmic and stationary potentials; the other was made of sporadically occurring potentials that were either propagating (at a speed of 8.4 +/- 2.5 cm/s, mean +/- SD) or nonpropagating. Food intake provoked a significant increase in both the propagating potentials (from 2.6% to 7.7% of the recording time, p less than 0.05) and the nonpropagating potentials (from 15.8% to 34.8% of the recording time, p less than 0.05). No significant change was observed for the stationary rhythmic potentials. After the meal, the sporadic nonpropagating spiking activity showed a first peak within 10-20 min and another peak within 60-70 min. Propagating spiking activity only showed one peak 70-80 min after the meal.

Inhibition of canine duodenal interdigestive myoelectric complex by nutrient perfusion of jejunal and ileal Thirty-Vella loops.

The mechanisms by which the intestinal interdigestive myoelectric complex (IDMEC), recurring at about 90 minute intervals in the fasted dog, is disrupted by feeding remain unknown. We investigated whether the IDMEC could be disrupted in the duodenum by perfusing a Thiry-Vella loop with glucose in the dog. An intestinal Thiry-Vella loop, measuring one half (80 to 160 cm) of the total length of the small bowel was constructed in four dogs from the jejunum, and in four other dogs from the ileum. Extracellular nichrome electrodes were sewn on the duodenum for recording the electrical activity of the intestine. After three weeks' recovery, electrical recordings were performed in the fasted dogs in order to observe whether the IDMEC persisted in the duodenum when the Thiry-Vella loops were perfused, at different days, for four hours with solutions made of either (1) NaCl 154 mM, (2) NaCl 308 mM, (3) glucose 300 mM, or (4) glucose 600 mM, at a rate of 8 ml/min. NaCl 308 mM and glucose 600 mM were also delivered at a rate of 4 ml/min. Glucose output from the Thiry-Vella loops was measured throughout the experiments over consecutive five minute intervals. Each experiment was performed three times in each dog. The results showed that perfusing the Thiry-Vella loops with NaCl 154 mM or NaCl 308 mM did not suppress the IDMEC in the duodenum whether the flow rate was 4 or 8 ml/min. On the contrary, perfusing the jejunal loops with glucose 300 mM disrupted the IDMEC in 54% of the experiments; perfusing glucose 600 mM disrupted the IDMEC in 83% of the experiments. In the ileal Thiry-Vella loop experiments, the IDMEC was disrupted in 33% of the cases with glucose 300 mM and in 66% of the cases with 600 mM. No significant difference was observed with glucose 300 mM delivered at a rate of 8 ml/min and glucose 600 mM delivered at a rate of 4 ml/min. Finally, the inhibitory effect of perfusing the Thiry-Vella loops with glucose increased as the amount of absorbed glucose increased. These results indicate that interruption of the IDMEC by feeding probably involves extraintestinal factors. These factors do not seem to be specific for any one part of the small intestine, but they seem to be activated by intestinal absorption.

Inhibition of canine interdigestive proximal gastric motility by cholecystokinin octapeptide.

Feeding abolishes cyclic interdigestive motility and decreases intraluminal pressure in autotransplanted pouches of canine proximal stomach. Our aim was to determine whether cholecystokinin might be the hormonal messenger involved. In four conscious dogs with autotransplanted proximal gastric pouches and chronic duodenal electrodes, intrapouch pressure and duodenal myoelectric activity were measured during fasting, while cholecystokinin octapeptide (CCK-OP) was infused intravenously for 4 h at doses 0, 15, 31, 62, 125, and 250 mg . kg-1 . h-1. Each dose was given five times to each animal. Cholecystokinin octapeptide inhibited the interdigestive cycles in both pouch and duodenum and decreased the pressure in the pouch. The threshold for these effects was 31 ng . kg-1 . h-1, and the ED50 was 62 ng . kg-1 . h-1. The dose of 125 ng . kg-1 . h-1 suppressed the cycles nearly completely and decreased mean +/- SE intrapouch pressure from 15.3 +/- 1.1 to 6.3 +/- 2.8 cmH2O . min (P less than 0.001). After the infusions were stopped, cyclic activity and intrapouch pressure returned promptly to control values. We concluded that CCK-OP at "physiological" doses abolished interdigestive cycles and decreased intraluminal pressure in autotransplanted pouches of canine proximal stomach.