Fecal short-chain fatty acid concentrations and effect on ileal pouch function.

Random stool samples were obtained from 14 ileal pouch-anal anastomosis (IPAA) patients 43 +/- 5 (mean +/- SEM) months after surgery, and the concentrations of individual short-chain fatty acids (SCFAs) were determined by gas liquid chromatography. Stool frequency was determined from a diary recorded for 15 days prior to stool sampling. The frequency, amplitude, and duration of phasic contractions (PCs) within the pouch following infusion of a physiologic concentration of SCFAs and normal saline randomly into the pouch of six IPAA patients were determined manometrically. The mean total SCFA concentration after IPAA did not differ significantly from normal stools (83 +/- 20 mM after IPAA vs. 97 +/- 10 mM for controls; P > 0.05). In the IPAA patients, regression analysis demonstrated an inverse relationship between stools per day and total SCFA concentration (r = 0.73; P < 0.001). Moreover, no change in frequency (3.0 +/- 0.9 vs. 3.2 +/- 0.8 PCs/30 minutes), amplitude (26 +/- 5 vs. 25 +/- 4 mmHg), or duration (23 +/- 3 vs. 26 +/- 2 seconds) of PCs was found after SCFA infusion compared with saline control (P > 0.1). These findings demonstrate that SCFAs are present in ileal pouch effluent and that stool frequency may be related to fecal SCFA concentration. Also, the normal contractile response of the terminal ileum to SCFAs does not occur in the ileal pouch.

Ileocolonic transit does not change after right hemicolectomy.

The role of the human ileocolonic junction in the transit of solid contents through the entire gut was evaluated. Eight patients, well compensated after right hemicolectomy for localized colon cancer, and eight age-matched healthy controls were enrolled. Scintigraphic transit was quantified after subjects ingested a mixed meal containing 111In-labeled Amberlite beads (average diameter, 1 mm; Sigma Chemical Co., St. Louis, MO). Gastric emptying was initially faster in the postoperative group, but overall emptying was not different from controls; small bowel transit also did not differ between the groups. In patients in whom the distal ileum, ileocolonic sphincter, and proximal colon were absent, isotopes moved from small to large bowel in a manner that was qualitatively and quantitatively no different from that of controls. Major episodes of coloileal reflux could not be identified in either group. After hemicolectomy, the residual transverse colon, and to a lesser degree the descending colon, were able to store solid residue, although in lesser amounts than the unoperated large bowel. The ileocolonic sphincter in humans appears to play only a minor role, at most, in ileocolonic transit, and the colon remaining after right hemicolectomy stores residue so that bowel habits are not greatly disturbed.

Colonic tone and motility in patients with irritable bowel syndrome.

In this study, our aim was to test the hypothesis that colonic tone is abnormal in patients with irritable bowel syndrome (IBS). We studied eight patients with IBS and eight age-matched asymptomatic control subjects, in whom tone and motility were measured by an electronic barostat and by pneumohydraulic perfusion manometry, respectively. Tone and motility were recorded from the descending colon for a 14-hour period--3 hours awake, 7 hours asleep, 2 hours fasting after awakening, and 2 hours postprandially. In patients with IBS and in healthy subjects, colonic tone decreased by up to 50% during sleep and increased promptly on awakening. Fasting colonic tone (as quantified by the volume in the barostat balloon) in the awake state was not significantly higher in patients with IBS than it was in healthy subjects (125 +/- 13 versus 152 +/- 15 ml; P = 0.19). Tone increased postprandially in both study groups, and the increase was greater in healthy subjects than it was in patients with IBS (P < 0.05). The motility index during fasting was greater in patients with IBS than it was in healthy control subjects (3.2 +/- 0.6 versus 1.6 +/- 0.4; P = 0.05), and the postprandial increase in motility index was greater in the healthy subjects. Preprandially and postprandially, we noted a trend for high-amplitude prolonged contractions to be more frequent in patients with IBS than in healthy subjects. We conclude that colonic tone in patients with IBS showed the same nocturnal and postprandial variations as it did in healthy subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Variation of muscle tone in the human colon.

It was hypothesized that the human colon is able to relax or constrict to receive materials arriving from above or to hasten distal passage of contents. Dilatation is also a feature of several pathophysiological states and, therefore, the propensity of the colon to dilate might be important in disease. An electromechanical barostat was applied to the human colon, and changes in colonic tone were recorded in response to physiological perturbations. In 16 studies of 14 healthy volunteers, the colon was prepared for colonoscopy and a manometry-barostat assembly was positioned in the ascending (n = 5), transverse (n = 4), or descending (n = 7) colon. The influences of food and overnight sleep were recorded. The barostat continuously monitored, at a constant pressure, the volume of air within a highly compliant 10-cm bag. Changes in tone, as reflected by changes in bag volume, were usually unassociated with waves of intraluminal pressure recorded from adjacent manometric sites. Thus, the barostat revealed a motor phenomenon not readily apparent by conventional manometry. Food caused an immediate though slowly progressive increase in tone; however, bag volumes were greatest during overnight sleep and were decreased on waking. The barostat has the potential to explore another possibly important aspect of colonic function in humans.

Canine ileocolonic sphincter: flow, transit, and motility before and after sphincterotomy.

Our hypothesis was that the canine ileocolonic sphincter (ICS), per se, would have little regulatory effect on the transit of chyme from ileum to colon. We argued, from earlier observations, that the ileocolonic junction was influenced more by functional motor integration of the ileum, ICS, and proximal colon. In five dogs, the ileocolonic sphincter was ablated by extramucosal sphincterotomy; the operation significantly lowered tonic pressures at the ICS. Animals were then studied in the fasting state and postprandially. Ileal flow was estimated by marker dilution, and ileocolonic flow was estimated by total recovery of chyme from a colonic cannula. Transit times were measured after the bolus infusion of nonabsorbable markers. Ileocolonic sphincterotomy did not significantly alter flow rates or transit times of chyme across the ICS, although ileal motor patterns were changed after sphincterotomy. We concluded that the ICS probably has only a small effect on transit and flow at the ileocolonic junction. These findings argue for the importance of integrated motility of the ileum, ICS, and proximal colon in controlling the flow of chyme in this region.

Sensitivities of human jejunum, ileum, proximal colon, and gallbladder to cholecystokinin octapeptide.

We compared in humans simultaneous motor responses of the jejunum, ileum, proximal colon, and gallbladder (GB) to intravenous cholecystokinin octapeptide (CCK-OP). To gauge the physiological relevance of the doses of CCK-OP, intestinal motility and GB contraction were also quantified after a fatty meal. Eight healthy volunteers participated in both experiments. Six graded, 30-min intravenous infusions had a mean range of 2.2 to 73.2 pmol X kg-1 X h-1 of CCK-OP; these spanned from subphysiological (negligible contraction of GB) to pharmacological (producing intestinal symptoms and a 70-99% contraction of GB) levels. CCK-OP inhibited interdigestive cycles of motility, though in some persons fasting patterns persisted with doses of CCK-OP, which produced up to 50% reduction in GB volume. Motility indices of the ileum and proximal colon responded to CCK-OP by decreasing initially but then increasing with larger doses; motility of the jejunum increased gradually at all doses. Judged by the gallbladder's response to food (reduction in volume down from 74 to 29% of original volume), the physiological range of infused CCK-OP was approximately 5-16 pmol X kg-1 X h-1. Within this range of doses of CCK-OP, motility of the jejunum increased, whereas motility of the proximal colon was reduced. These data are consistent with CCK being a "physiological" mediator of intestinal motility in humans; responses of the intestine to the peptide appear to vary regionally.

Human interdigestive motility: variations in patterns from esophagus to colon.

In most fasting mammals, motility of the foregut and small intestine undergoes regular cycles of activity. Much of the expanding knowledge of this phenomenon comes from species other than humans; however, disorders of these patterns are proposed as being clinically important. We report studies in 16 healthy humans in whom motility was recorded from intraluminal pressure sensors, both when fasting and after a meal, for prolonged periods. The recording system spanned the area from stomach to proximal colon in all subjects and included the lower esophagus in 11 of the 16 studied. Half the interdigestive cycles involved the esophagus, approximately one-third began in the gastroduodenal region, and the remainder commenced more distally. Fewer than half the migrating motor complexes were recognizable beyond the midpoint of the small bowel, and less than 10% reached the distal ileum. The migrating motor complex was more prominent at night; and its progression through the jejunum was then slower. Small meals (345-395 kcal) interrupted fasting patterns for 90-240 min, but the amount of fat did not influence the duration of these disruptions. Motility varied widely between and within individuals, and differences between normal patterns in the jejunum and ileum were particularly striking. Thus, levels of recordings must be defined accurately if putative abnormalities, of possible clinical significance, are to be interpreted correctly. Relating local motor patterns to the maximal rate of rhythmic contractions, which reflects the frequency of slow waves and is a guide to the level of the small bowel, may be helpful in this regard.

Sulfapyridine appearance in plasma after salicylazosulfapyridine. Another simple measure of intestinal transit.

The appearance of sulfapyridine in plasma after oral administration of salicylazosulfapyridine (SASP) was evaluated as a method for defining arrival time in the cecum, an index of small bowel transit. After direct instillation of SASP and lactulose into the cecum, the appearances of their metabolites (sulfapyridine in plasma and hydrogen in breath) were rapid (1-10 min) and simultaneous. When a mixture of SASP and lactulose was taken by mouth, times of the respective "signals" varied among individuals from 40 to 180 min (n = 8) but were correlated within individuals. Salicylazosulfapyridine transit times from duodenum to cecum were also very similar to simultaneous measurements of transit by scintigraphic monitoring of technetium 99m. Timing of the sulfapyridine signal corresponded to the arrival of 5%-13% of technetium 99m DTPA in the cecum. Exemplifying the use of this new technique, simultaneous administration of lactulose into the stomach and SASP into the duodenum yielded consistently longer stomach-to-cecum than duodenum-to-cecum transits, attributable to the delay caused by gastric emptying. Therapeutic doses of morphine delayed small bowel transit of SASP. Transit of SASP offers a second marker technique for the cecal arrival of the "head" of a bolus; the approach may be useful as an inexpensive, noninvasive measurement of transit.

Passage of carbohydrate into the colon. Direct measurements in humans.

To quantify passage of unabsorbed dietary starch into the colon, 7 healthy volunteers had a multilumen tube positioned close to the ileocecal junction. Marker solution was perfused slowly, 20-40 cm above an aspiration site, to estimate, by marker dilution, flow through the ileum. On consecutive days, subjects ate liquidized meals containing 20 or 60 g starch; ileal aspirates were analyzed for starch and glucose for 5-6 h fasting and 4-7 h postprandially. Volume and carbohydrate concentrations were used to derive total carbohydrate traversing the ileum. In different subjects, unabsorbed carbohydrate was 453-4023 mg (2.3%-20.1%, mean 9.3%) for the smaller meal and 1332-6352 mg (2.2%-10.4%, mean 6.0%) for the larger. In 4 volunteers, hydrogen breath tests were performed on separate occasions after sucrose (50 g), lactulose (26 g), and the 20-g meal. Lactulose increased hydrogen excretion; sucrose and the test meal did not. We conclude that 2%-20% of dietary starch escapes absorption in the small bowel, confirming others' results using breath tests alone. Breath tests, though more convenient than intubation studies, may be a less sensitive index of starch malabsorption.

Proximal gastric vagotomy and mucosal antrectomy: a possible operative approach to duodenal ulcer.

Our aim was to develop proximal gastric vagotomy with mucosal antrectomy as an operative approach to duodenal ulcer. We performed mucosal antrectomy in four dogs by excising the antral mucosa via a circular corporal myotomy, removing a circumferential band of corporal seromuscularis, anastomosing the corporal and pyloric mucosas endoantrally, and reapproximating the corporal and antral seromuscularis. Gastric emptying and serum gastrin were assessed before and 4 weeks after operation. A second operation, proximal gastric vagotomy, was then done, and the tests were repeated 4 weeks later. The concentration of gastrin in the serum during fasting was lower after mucosal antrectomy than before operation, as was the postprandial concentration; the values remained low after proximal gastric vagotomy. Gastric emptying of liquids and indigestible solids was unaltered by mucosal antrectomy or mucosal antrectomy plus proximal gastric vagotomy. The emptying of digestible solids was slowed somewhat by mucosal antrectomy to 75% of the control rate, but no further change was found after proximal gastric vagotomy. We concluded that mucosal antrectomy eliminated the gastrin-producing antral mucosa and, in combination with proximal gastric vagotomy, did not greatly alter gastric emptying of liquids or solids. The combined operation might have a role in the surgical treatment of duodenal ulcer.

Cytotoxicity of ricinoleic acid (castor oil) and other intestinal secretagogues on isolated intestinal epithelial cells.

Epithelial cells were isolated from hamster small intestine by a technique of vibration and used to measure cytotoxicity in vitro of certain substances known to stimulate intestinal fluid secretion. These secretagogues have laxative properties and produce mucosal damage in vivo. Compounds tested were ricinoleic acid (caster oil), dioctyl sodium sulfosuccinate, oleic acid, sodium deoxycholate and sodium cholate. Cytotoxicity was assessed by: 1) exclusion of trypan blue; 2) release of intracellular (prelabeled) 51Cr; and 3) inhibition of cellular uptake of 3-O-methylglucose. Ricinoleate produced a dose-dependent (0.1-2.0 mM) cytotoxicity as assessed by all three methods. Oleic acid, a nonhydroxylated analog of ricinoleate, was less potent. The dihydroxy bile acid, deoxycholate, was equipotent with ricinoleate, was less potent. The dihydroxy bile acid, deoxycholate, was equipotent with ricinoleate but its trihydroxy congener, cholate, was less potent. Dioctyl sodium sulfosuccinate had cytotoxicity similar in magnitude to that of ricinoleate and deoxycholate. Cytotoxicity of these agents to isolated cells may relate to their secretory potential in vivo, their abilities to produce structural change at the mucosal surface and their laxative properties.