Effect of cholecystokinin octapeptide and atropine on human colonic motility, tone, and transit.

The role of cholecystokinin (CCK) in postprandial control of colonic motility is controversial. To test the hypothesis that CCK stimulates colonic tone, motility, and transit we measured these colonic functions in 16 healthy subjects using intraluminal manometry, barostatic balloon measurements, and radioscintigraphy. This was a randomized-order, double-blind, sequential study design in each subject of saline and either atropine (0.01 mg/kg stat and 0.01 mg/kg/hr by infusion) or CCK-octapeptide (OP, 30 ng/kg stat and 60 ng/kg/hr by infusion). Atropine was used as control to demonstrate responsiveness of selected parameters of colonic motility. Atropine significantly reduced whole colon (change from fasting = 52 +/- 11%) and left colon (change from fasting 61 +/- 8%) phasic pressure activity and transverse colon tone (change from fasting 159 +/- 40%); CCK-OP had no significant effects on phasic contractility, tone or transit. Thus, a CCK-OP infusion that maximally stimulates pancreatic exocrine secretion and gallbladder contraction has no effect on motor function or transit in prepared colon of healthy subjects.

Motility and tone of the left colon in constipation: a role in clinical practice?

OBJECTIVES: Colonic motor mechanisms deranged in constipation are not understood completely. Our aim was to measure left colonic motility and tone, during fasting and postprandially in patients with chronic constipation. METHODS: During 1 h fasting and 2 h postprandially, we measured pressures (multilumen manometry) and tone (barostat) in the left colon of 15 healthy controls and 40 patients with chronic constipation associated with slow (n = 15) or normal colonic transit (n = 12) or outlet obstruction (n = 13). RESULTS: Fasting tone was similar in all groups, and all demonstrated a significant increase in motor activity to food. There was lower postprandial tone (p < 0.05) in the slow transit and outlet obstruction groups. There were no differences in the timing of the tonic response or the number or amplitude of high-pressure propagated contractions. The slow transit group had lower postprandial phasic responses in the rectosigmoid (p < 0.05) and descending (p < 0.1) colon; the outlet obstruction group had lesser descending (p < 0.05) and rectosigmoid (p < 0.1) colon phasic motility. CONCLUSIONS: Colonic intraluminal measurements alone do not discriminate subgroups of chronic constipation more accurately than transit and pelvic floor tests, and currently have a limited role in clinical practice. However, manometry and tone measurements may be helpful in confirming a diagnosis of slow transit constipation (colonic inertia) in patients considered candidates for surgical treatment.

Hyperventilation, central autonomic control, and colonic tone in humans.

Symptoms attributable to hyperventilation are common among patients with the irritable bowel syndrome (IBS); indeed, some have suggested that hyperventilation may exacerbate the alimentary symptoms of IBS. Hyperventilation changes haemodynamic function through central and peripheral mechanisms; its effects on colonic motor function, however, are unknown. The aim of this study, therefore, was to assess the effects of hyperventilation on colonic tone and motility and on cardiovascular autonomic activity, and to discover if hypocapnia was critical to elicit the response. Phasic and tonic motility of the transverse and sigmoid colon, end tidal PCO2, pulse rate, and beat to beat pulse variability were assessed before, during, and after a five minute period of hypocapnic hyperventilation in 15 healthy volunteers; in seven other subjects, effects of both eucapnic and hypocapnic hyperventilation were evaluated. Hypocapnic but not eucapnic hyperventilation produced an increase in colonic tone and phasic contractility in the transverse and sigmoid regions and an increase in pulse rate and pulse interval variability. The findings are consistent with inhibition of sympathetic innervation to the colon or direct effects of hypocapnia on colonic smooth muscle, or both. These physiological gut responses suggest that some of the changes in colonic function are caused by altered brain or autonomic control mechanisms.

Differences in colonic tone and phasic response to a meal in the transverse and sigmoid human colon.

It is not yet clear whether the regional differences in the physical properties of the colon influence its motor responses. Tonic and phasic colonic motility and compliance of the transverse and sigmoid colon were therefore assessed using a combined barostat-manometry assembly in 22 healthy subjects. Measured colonic compliance was corrected by subtraction of the compliance of the closed barostat system. The mean (SEM) preprandial colonic volumes in the transverse and sigmoid colon were similar (150 (12) and 128 (13) ml, p = NS), corresponding to calculated mean (SEM) colonic diameters of 4.3 cm and 4.0 cm respectively. The mean increase in colonic tone postprandially was significantly greater in the transverse (24.1% (3.5)) than in the sigmoid colon (13.1% (3.0), p < 0.01). The mean increase in phasic contractility was significantly greater, however, in the sigmoid than in the transverse colon (1270 (210) and 425 (60) mm Hg/90 min respectively, p < 0.01). Compliance was greater in the transverse than sigmoid colon (7.6 (0.44) and 4.1 (0.15) ml/mm Hg, p < 0.001). The fasting volume of the colon was significantly correlated with the magnitude of the tonic response to the meal in the transverse and sigmoid colon (p < 0.001 for both). In conclusion, there are quantitatively different but qualitatively similar phasic and tonic responses to the meal in the two colonic regions. Differences in the viscoelastic and luminal dimensions may partly account for these differences in tonic responses.

Effect of octreotide on gastrointestinal pressure profiles in health and in functional and organic gastrointestinal disorders.

The somatostatin analogue, octreotide, restores normal pressure profiles in disorders of upper gut motility. This study aimed to evaluate the acute effects of octreotide in five healthy subjects and in 50 consecutive patients with functional (n = 22) or organic (n = 28) dysmotility. Antroduodenojejunal manometry was performed during three hours' fasting, for two hours after a standard meal, and 30 minutes after subcutaneous injection of 50 micrograms octreotide. Antral motility, before and after octreotide, and characteristics of spontaneous migrating motor complexes and octreotide induced activity fronts were compared. Octreotide inhibited antral motility and induced a small intestinal activity front followed by motor quiescence in all healthy subjects and patients. The duration and propagation velocity of activity fronts were greater than those of spontaneous migrating motor complexes. Thirty per cent of activity fronts began simultaneously at different levels of small bowel, and in 20%, a second, normally propagated activity front developed within 30 minutes of octreotide injection. Octreotide induces rapidly propagated, long activity fronts, even in patients with neuropathology, and this may initially facilitate the intestinal propulsion of chyme. Propulsion may not occur, however, if octreotide induces simultaneous activity fronts or if the activity front is followed by prolonged quiescence. Inhibition of antral motility suggests that octreotide may not be effective in gastroparesis.