Effect of cholecystokinin on rectal motor and sensory function in patients with irritable bowel syndrome and healthy controls.

AIM: Ingestion of a meal frequently induces an urge to defaecate, the so-called gastro-colonic or gastro-rectal reflex. In patients with irritable bowel syndrome (IBS), symptoms are often provoked by meals. Cholecystokinin (CCK), a proximal gut peptide released after ingestion of a meal, may mediate these postprandial changes. The potential role of CCK in rectal sensory and motor function was evaluated by a rectal barostat study in healthy controls and patients with IBS. METHOD ; The sensory effects on serosal and mucosal receptors were studied. Twelve healthy controls and 12 patients with IBS underwent a ramp distension procedure of the rectum during infusion of CCK and placebo in random order. In 10 other healthy controls and 10 IBS patients an intermittent distension procedure was performed during infusion of CCK and placebo in random order. RESULTS: No differences were found in rectal compliance during ramp distensions between IBS patients and controls. CCK did not affect perception of urge and pain in controls or in IBS patients. Similar results were obtained during the intermittent distensions, but at higher distension pressures CCK significantly increased rectal sensitivity in IBS patients. CONCLUSION: Infusion of exogenous CCK to plasma levels normally seen in the postprandial state did not influence rectal motor function or sensations during ramp distension but it did significantly increase pain sensation in IBS patients during rapid intermittent distension.

Recto-colonic reflex is impaired in patients with irritable bowel syndrome.

Motor and sensory dysfunction of the gut are present in a subset of patients with irritable bowel syndrome (IBS). Recent studies have demonstrated the presence of a recto-colonic inhibitory reflex in healthy humans. It is not known whether this reflex exists in IBS. We studied rectal compliance, perception and the recto-colonic reflex by measuring volume responses of the descending colon to rectal distentions by barostat in 26 IBS patients and 13 healthy controls under both fasting and postprandial conditions. In the fasting state, rectal distention inhibited colonic tone and phasic motility to a similar extent in health and IBS. After a meal, rectal distention inhibited colonic tone and phasic motility to a lesser degree (P < 0.05) in IBS than health. Under postprandial but not fasting conditions, rectal distentions of increasing intensity were associated with higher pain scores in IBS than in health. Rectal distention inhibits tonic and phasic motility of the descending colon in healthy controls and in IBS patients. Postprandially this recto-colonic inhibitory reflex is impaired and attenuated in IBS patients compared with controls. These findings point to an altered reflex function in IBS and have implications for pathophysiology and therapy.

Compliance, tone and sensitivity of the rectum in different subtypes of irritable bowel syndrome.

Irritable bowel syndrome (IBS) consists of various subtypes. It is not known whether these subtypes share a common pathophysiology. Evaluation of motor and sensory function of the rectum using a barostat may help to explore a common pathophysiological background or differences in pathophysiology in subtypes of IBS. We have evaluated compliance, tone and sensitivity of the rectum, in both fasting state and postprandially, using a computerized barostat in 15 patients with diarrhoea-predominant IBS (IBS-D), 14 patients with constipation-predominant IBS (IBS-C) and compared the results with those obtained in 12 healthy controls. Rectal compliance as calculated over the steep part of the pressure-volume curve (17-23 mmHg) was decreased in both IBS groups (IBS-D 8.0 +/- 1.4 mL mmHg-1; IBS-C 5.6 +/- 1.1 mL mmHg-1) compared with controls (24.7 +/- 3.5 mL mmHg-1). The perception of urge was increased only in IBS-D patients, whereas pain perception was significantly increased in both IBS groups. Spontaneous adaptive relaxation was decreased in IBS-D patients. Postprandially, rectal volume decreased significantly in the controls and in IBS-D patients, but not in IBS-C patients. In conclusion, both rectal motor and sensory characteristics are different between IBS-D and IBS-C patients. Therefore, testing of rectal visceroperception, adaptive relaxation and the rectal response to a meal may help distinguish groups of patients with different subtypes of irritable bowel syndrome.

Does Helicobacter pylori gastritis affect motor function of proximal stomach in dyspeptic patients?

The role of Helicobacter pylori infection in proximal gastric motor function and its relation to symptoms in patients with functional dyspepsia is still unclear. We prospectively studied 26 patients with dyspepsia, no structural abnormalities found during endoscopy and biopsy-proven Helicobacter pylori-positive gastritis before and three months after Helicobacter pylori treatment. We used an 11-item score list to evaluate symptoms, gastric biopsies for histology, and a gastric barostat (isobaric inflation-deflation) for proximal gastric motility. Minimal distending pressure (MDP), mean gastric volume at operating pressure, AUC of inflation-deflation cycles, and hysteresis (difference in AUC during inflation and AUC during deflation) were calculated. After three months, Helicobacter pylori was eradicated in 96% of patients. MDP, mean gastric volume at operating pressure, gastric compliance, and hysteresis did not change significantly. Aggregate symptom score as well as histology scores in antrum and corpus decreased significantly. Reduction in postprandial pain correlated with a change in hysteresis (r = 0.567, P < 0.01), but other symptoms did not. Reduction of corpus inflammatory activity correlated with changes in hysteresis (r = 0.604, p < 0.005), suggesting that the stomach attains it original shape faster when inflammation is reduced. These observations suggest that inflammatory changes or release of inflammatory substances associated with Helicobacter pylori infection may influence proximal gastric motor characteristics.

Influence of gender on proximal gastric motor and sensory function.

OBJECTIVE: Gender-related differences have been demonstrated with regard to GI motility: gallbladder contraction, colonic transit, and gastric emptying are delayed in women. It is not known whether gender influences proximal gastric motility and perception. METHODS: We have studied the influence of gender on proximal gastric motility and perception under fasting and postprandial conditions by retrospective analysis of data obtained in 99 healthy volunteers (42 men, 57 women) who participated in barostat studies performed according to standardized protocols at the Leiden University Medical Center (Leiden, The Netherlands) between 1996 and 2000. RESULTS: Minimal distending pressure (MDP) was significantly higher in women than in men (respectively, 6.8+/-0.2 vs 5.5+/-0.2 mm Hg; p < 0.001). During stepwise pressure distensions pressure-volume curves were similar in both sexes after correction for MDP, whereas perception of fullness and abdominal pressure increased significantly (p < 0.05) more rapidly in women. Before the meal intragastric volumes (at MDP + 2 mm Hg) did not differ between sexes. After the meal gastric relaxation in the first 30 min did not differ in women and men (respectively, 186+/-23 ml and 140+/-32 ml). However, from 30 until 90 min after the meal a significantly (p < 0.05) delayed return of intragastric volume to basal was seen in women. Perception of postprandial nausea was significantly (p < 0.01) increased in women. Perception of postprandial fullness remained increased for a longer period of time in women. CONCLUSIONS: Proximal gastric motility and perception are influenced by gender. Gender-related differences in postprandial proximal gastric motility and perception should be taken into account in barostat studies comparing patients with controls.

Role of cholecystokinin in relaxation of the proximal stomach.

Ingestion of a meal causes proximal gastric relaxation (accommodation). The magnitude of accommodation is related to the fat content of the meal. A role for cholecystokinin (CCK) has been suggested. However, under fasting conditions intravenous CCK to postprandial levels does not induce a similar accommodation. This study further explores the role of CCK in accommodation. A gastric barostat was used in eight healthy persons to study accommodation in response to a carbohydrate meal with intravenous CCK (CH-CCK), carbohydrate meal with intravenous placebo (CH-placebo) and a fat rich meal with intravenous placebo (FAT). VAS scores for satiety and plasma CCK levels were obtained. In the first postprandial hour the FAT meal induced a relaxation of 112 +/- 29 ml, the CH-CCK meal 49 +/- 36 ml and the CH-placebo meal 12 +/- 32 ml (FAT versus CH-placebo P = 0.03; FAT versus CH-CCK P = 0.09). In the second postprandial hour, intragastric bag volume returned to baseline with all meals. The FAT meal had the most pronounced effect with respect to satiety, CH-placebo the least. In the first postprandial hour, plasma CCK levels increased with the CH-CCK and FAT meals but not with the CH-placebo meal; in the second postprandial hour, levels remained elevated with the CH-CCK meal. It is concluded that a carbohydrate meal with exogenous CCK does not induce fundic relaxation, whereas a fat-rich meal (endogenous CCK) does, despite similar plasma CCK levels.

Motor and sensory function of the rectum in different subtypes of constipation.

BACKGROUND: It is not known whether evaluation of motor and sensory function of the rectum using a barostat may help to distinguish subtypes of constipation. METHODS: Motor and sensory function of the rectum have been evaluated using a barostat in 14 patients with slow transit constipation (STC), 12 patients with constipation-predominant irritable bowel syndrome (IBS) and 18 healthy controls. First minimal distending pressure was determined, after which spontaneous adaptive relaxation of the rectum was monitored. Then a step-wise isobaric distension procedure was performed, during which symptom perception was determined. The distension was followed by a 90-min barostat procedure: for 30 min in the basal state followed by ingestion of a semi-liquid meal (postprandial state). RESULTS: Minimal distending pressure was not different between both patient groups and controls, neither was compliance different between constipated patients and controls. The degree of spontaneous adaptive relaxation was in the same range in all groups. During distensions with high pressures, the perception of urge was significantly reduced in STC patients compared to IBS and controls, while the perception of pain was significantly increased in IBS versus STC and controls. Postprandially, a small decrease of rectal volume was only observed in the control group, but not in the patients. CONCLUSIONS: Rectal motor characteristics are not different between patients with constipation-predominant IBS, patients with STC and healthy controls while during isobaric distensions, sensations of urge were reduced in STC and sensations of pain were increased in IBS. Rectal visceroperception testing may help distinguish groups of patients with different subtypes of constipation.

The role of the barostat in human research and clinical practice.

BACKGROUND: The barostat is a recently developed device used to study the physiology and pathophysiology of the motor and sensory functions of the gastrointestinal tract. It can monitor volume changes while maintaining a set constant pressure and deliver controlled distensions of gastrointestinal organs. Simultaneously, motility and visceral perception may be assessed. The barostat has contributed to the understanding of physiological processes in the gastrointestinal tract with regard to regulation of tone, compliance, enteric reflexes, sensation and processing of signals to and from the gut. In addition, the barostat has been used to study various gastrointestinal disorders. In functional bowel disorders, objective abnormalities in visceral sensitivity and enteric reflexes have been demonstrated. Numerous other diseases, gastrointestinal in origin as well as systemic diseases affecting the gut, have been studied. In the near future, the barostat may become a clinically useful tool for the objective diagnosis of motor and sensitivity disorders of the gut and for monitoring the effectiveness of therapy.