Effects of a meal and bisacodyl on colonic motility in healthy volunteers and patients with slow-transit constipation.

In the present study, the gastrocolonic response after ingestion of a standardized liquid meal and the response to a local chemical stimulus were investigated in 10 healthy volunteers and 10 patients with slow-transit constipation (as determined by marker studies). Colonic pressures were recorded while fasting, after ingestion of a standardized meal and after intracolonic bisacodyl infusion, using a 12-channel water-perfused catheter. Pressure waves propagating over at least 20 cm (HAPPW) were identified visually and automated analysis was carried out on remaining segmental motility. Increases of motility after a meal and bisacodyl were seen in healthy subjects, whereas patients did not show these responses. The time until occurrence of the first HAPPW after bisacodyl infusion tended to be prolonged (4.3 +/- 1.4 vs 36.1 +/- 15.3; P = 0.053) and the number of HAPPWs in the first 30 min. after infusion was lower compared to healthy subjects (2.1 +/- 0.2 vs 5.4 +/- 0.3; P < 0.01). The percentage of HAPPWs that were experienced as urge or cramp was significantly lower in constipated patients (53 +/- 3% vs 95 +/- 1%; P < 0.005). In conclusion, this study shows that in patients with slow-transit constipation, the colonic motor response to a meal and to bisacodyl, as well as the perception of bisacodyl-induced propagated pressure waves is decreased.

Fully automated analysis of colonic manometry recordings.

The purpose of this study was to develop a computer program for fully automated analysis of all presently known motor patterns in human colonic motility recordings. Colonic pressure recordings obtained from 24 healthy volunteers were used. Algorithms were developed for the detection and numerical analysis of five types of pressure waves: antegrade, retrograde, simultaneous, high-amplitude and isolated pressure waves. Furthermore, periodical motor activity was quantified. Validation was performed by comparison with visual analysis by two experienced observers. Patterns recorded during day- and night-time were compared using multiple-factor analysis of variance with Bonferroni correction. Automated analysis correlated well with visual peak detection (r = 0.98, P <0.01) and detection of antegrade pressure waves (r = 0.98, P <0.01). Most motor patterns showed a diurnal variation. During the night, prevalences of antegrade (938 vs 455; P <0.05), retrograde (112 vs 81; P <0.05), high-amplitude (12.9 vs 1.3; P <0.05), isolated pressure waves (1114 vs 765; P <0.05), and periodic motor activity were decreased (7.33 vs 4.47%; P <0.05). However, when expressed as percentage of absolute numbers of pressure waves, prevalences remained constant. In conclusion, fully automated analysis of all hitherto described colonic motility patterns is feasible. During the night, overall wave prevalences markedly decreased, but the distribution over the various motor patterns was preserved.

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

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

The effects of the specific 5HT(4) receptor agonist, prucalopride, on colonic motility in healthy volunteers.

BACKGROUND: Prucalopride is a selective and specific 5-hydroxytryptamine(4) receptor agonist that is known to increase stool frequency and to accelerate colonic transit. AIM: To investigate the effect of prucalopride on high-amplitude propagated contractions and segmental pressure waves in healthy volunteers. METHODS: After 1 week of dosing (prucalopride or placebo in a double-blind, randomized, crossover fashion), colonic pressures were recorded in 10 healthy subjects using a solid-state pressure catheter with six sensors spaced 10 cm apart. Subjects kept diary records of their bowel habits (frequency, consistency and straining). High-amplitude propagated contractions were analysed visually, comparing their total numbers and using 10-min time windows. Segmental pressure waves were analysed using computer algorithms, quantifying the incidence, amplitude, duration and area under the curve of all detected peaks. RESULTS: When taking prucalopride, stool frequency increased, consistency decreased and subjects strained less. Prucalopride just failed to increase the total number of high-amplitude propagated contractions (P=0.055). The number of 10-min time windows containing high-amplitude propagated contractions was increased by prucalopride (P=0.019). Prucalopride increased the area under the curve per 24 h (P=0.026). CONCLUSIONS: The 5-hydroxytryptamine(4) receptor agonist prucalopride stimulates high-amplitude propagated contractions and increases segmental contractions, which is likely to be the underlying mechanism of its effect on bowel habits in healthy volunteers.

[Irritable bowel syndrome: pathophysiology and (future) treatment options]. / Het prikkelbaredarmsyndroom: pathofysiologie en (toekomstige) behandelingsmogelijkheden.

Abnormalities of intestinal motility, altered visceral perception and psychological influences are the most important factors in the pathogenesis of irritable bowel syndrome. Current pharmacological treatment options are limited and lack specificity. In the future, it is likely that a number of therapeutic agents with stronger spasmolytic effects (selective muscarinic receptor antagonists), more specific colokinetic properties (5-hydroxytryptamine (5HT)4 agonists) and a positive influence on visceral perception (serotonin (5HT3) receptor antagonists, kappa-agonists) will become available.

New developments in the treatment of irritable bowel syndrome.

The irritable bowel syndrome (IBS) is one of the most common gastrointestinal conditions encountered by general practitioners, and it accounts for a great deal of the workload of gastroenterologists in secondary care. Research to date indicates that several factors contribute to the development of IBS, of which disturbed gastrointestinal motility, altered visceral perception and psychosocial factors are regarded as the three most important mechanisms interacting in the development of this disorder. Most pharmacological research has been based on these insights. Several agents capable of modulating either motility or sensitivity are currently under investigation. Potential drugs in the treatment of diarrhoea-predominant IBS are the more selective antispasmodics, such as the M3-receptor antagonists (e.g. zamifenacin, darifenacin). In constipation-predominant IBS the colokinetic effects of the selective 5HT4 agonists prucalopride and tegaserod are of great interest. Since altered visceral perception is thought to play an important role in the genesis of abdominal pain and bloating in many patients with IBS, new drugs are targeted at modulating the sensitivity, such as 5HT3 antagonists (e.g. alosetron), kappa-agonists (e.g. fedotozine) and somatostatin analogues. Furthermore, psychosocial factors should not be overlooked, since these appear to be of great influence on the clinical outcome of IBS.