Effects of morphine and atropine on motility and transit in the human ileum

We examined motility of the ileocecal region, pressures at the ileocecal sphincter, and ileal flow after therapeutic doses of morphine and atropine. Using a factorial design in two cells of 8 (2(3] subjects, drugs were given during fasting and postcibally. Morphine (100 micrograms/kg body wt as a bolus intravenously) and atropine (7 micrograms/kg body wt as a bolus) stimulated migrating bursts of phasic activity (similar to phase III of the migrating motor complex). Morphine initially stimulated ileal flow, but atropine could not be shown to have this effect. Atropine reduced markedly the occurrence of sporadic pressure waves in the ileum, but morphine did not. Whereas atropine delayed mouth-to-ileum transit of polyethylene glycol, given in a mixed meal, morphine did not. Naloxone, in the dosage used (40 micrograms/kg body wt as a bolus, followed by 10 micrograms/kg body wt X h) had no independent effects on motility or flow, but did blunt the stimulatory effects of morphine and atropine on migrating motor complexes. We could not demonstrate an effect of any drug on the transit of lactulose from terminal ileum to cecum. Neither morphine nor atropine had impressive effects on tone at the ileocecal sphincter. These observations, while not specifying the mechanisms for constipation after opiates or anticholinergics, highlight the complexities of small bowel transit in humans and point out that the antidiarrheal effects of drugs are probably multifactorial.     

Effect of ileal infusion of intralipid on gastrointestinal transit, ileal flow rate, and carbohydrate absorption in humans after ingestion of a liquid meal

The effects of ileal infusion of Intralipid on the time required for a radiolabeled liquid starch meal to empty from the stomach and reach a point in the ileum that was 230 cm from the teeth and on the ileal flow rates and the degree of carbohydrate absorption were measured in 5 normal volunteers. The subjects were intubated with a four-lumen polyvinyl tube. Studies were carried out on consecutive days in random order. Infusion of fat into the ileum (a) slowed the transit of a liquid meal through the stomach, (b) delayed the arrival of the liquid meal in the ileum and increased its residence in the upper small intestine, (c) reduced the average flow of digesta through the upper small intestine and altered the pattern of flow, (d) reduced the volume of the meal entering the ileum, and (e) reduced the degree of carbohydrate absorption in the upper small intestine. These results suggest that the presence of fat in the ileum may have a profound influence on the digestion and absorption of a meal.     

Variability of motility of the ileum and jejunum in healthy humans

Motor patterns of the distal small bowel were defined in healthy humans, using a multilumen polyvinyl tube, passed by mouth in 11 healthy subjects. Five recording sites, spanning 100 cm of tube and featuring a nitrogen hydraulic infusion system, were used to obtain records during 6 h of fasting and 6 or more hours after ingestion of a 600-kcal liquid test meal. The loci of recordings were designated as jejunal, ileal, or terminal ileal, as judged by the length of tube within the intestine and by fluoroscopy. During fasting, the migrating motor complex was present in all subjects and at all levels of the small intestine, but it could not be traced into the colon. Interdigestive cycles were defined primarily by the presence of an "activity front" (phase 3 of the migrating motor complex). Ninety-six migrating motor complexes occurred each 97 min (grand mean for all loci), but intervals between individual activity fronts varied markedly (15-195 min), in contrast to what is reported in other species. The velocity of aboral migration was 4.7 +/- 1.8, 1.3 +/- 0.4, and 0.9 +/- 0.2 cm . min-1 (mean +/- SD) in jejunal, ileal, and terminal ileal, respectively. Rates of continuous, rhythmic contractions during activity fronts declined distally: 12.5 to 10.5 (jejunal), 10.9 to 9.3 (ileal), and 10.0 to 8.6 cycle/min (terminal ileal), respectively. In individual subjects, maximum rates of contraction and velocities of migration always declined distally, but the duration of activity fronts was unrelated to the level of recording. Food interrupted the fasting cycles of motility for periods ranging from 2.75 to greater than 10 h. The transition from the fasting to the fed pattern was prompt and the postprandial motility was that of irregular bursts of contractions interspersed with transient quiescence. These studied demonstrate that the migrating motor complex occurs throughout the human small intestine, and that inter- and intraindividual variations are marked; food disrupts the complex for variable periods. These variations must be considered when abnormalities are being sought in disease states.     

Emptying of the terminal ileum in intact humans. Influence of meal residue and ileal motility

Emptying of the terminal ileum was assessed in 15 healthy humans by injecting technetium 99m-diethyltriaminopentaacetic acid into the bowel through a multilumen orocolonic tube. The subsequent arrival of isotope in the colon was quantified by gamma-scintigraphy and colonic filling curves were obtained. Studies were performed during fasting (n = 5) cnd 2.5 h after either a low residue meal (n = 5) or a meal made high in residue (n = 5) by adding 4 g of guar. The time for 50% of the isotope to reach the colon (T50) was significantly accelerated after both meals, being 72 +/- 15 min for the high residue meal and 62 +/- 8 min for the low residue meal, compared with 183 +/- 37 min (p less than 0.01) in the 5 fasting subjects. Although the addition of guar did not alter T50 significantly, it did cause a significant fall in the rate of colonic filling, implying increased isotope dilution. Delay at the ileocolonic junction, as shown by plateaus in the middle of the colonic filling curves, was uncommon. Hold-up was significant in only 2 of 10 postprandial and 2 of 5 fasting studies. Rates of ileocolonic transit could not be related to either a mean ileal motility index or the occurrence of specific ileal motor patterns immediately proximal to the ileocolonic junction. Fasting ileocolonic transit was characteristically erratic but could not be related to interdigestive migrating motor complexes, which were rarely observed in the last 60 cm of ileum. We conclude that ileocolonic transit in humans is related to the rate at which material accumulates in the ileum, being rapid postprandially (when ileal flow is high) and slow and erratic during fasting. This method yields consistent results and could be used to define further factors that influence ileocolonic inflow.     

Effect of jejunal infusion of bile acids on small bowel transit and fasting jejunal motility in man.

The effect of jejunal infusion of glycochenodeoxycholic acid and glycocholic acid on small bowel transit time, fasting jejunal motility and serum bile acid concentrations was investigated in groups of five to six healthy subjects. Glycochenodeoxycholic acid at a concentration of 15 mmol/l (total amount: 5 mmol) and glycocholic acid 15 mmol/l (total amount: 5 mmol), both with lecithin 2.5 mmol/l, delayed (p less than 0.02) small bowel transit when compared with a bile acid free infusion [158.3 (12.5) min v 111.7 (17.6) min and 103.3 (21.8) min v 70.0 (14.9) min], inhibited (p less than 0.01 and p less than 0.05 respectively) the percentage duration of pressure activity of phase 2 [13.1 (1.8)% v 28.1 (3.4)% and 29.2 (5.5)% v 34.9 (3.9)%], but did not change duration of migrating motor complex, or of its phases. Glycochenodeoxycholic acid 10 mmol/l (total amount: 3.3 mmol), either with or without lecithin, did not delay small bowel transit significantly [145.0 (13.2) min v 115.0 (19.5) and 90.0 (11.7) min v 84.0 (8.3)]. When bile acids were infused, serum bile acid curves were similar to those obtained after a liquid meal and the peak serum bile acid concentration occurred 33.7 (6.6) min before (p less than 0.001) completion of small bowel transit. These observations suggest a role for endogenous bile acids in the regulation of small gut motility.     

Absorption of 7-ketolithocholic acid in rat jejunum, ileum and colon

7-Ketolithocholic acid is a bile acid which is formed in the intestine of man by bacterial oxidation of chenodeoxycholic acid and ursodeoxycholic acid. In contrast to deoxycholic acid and lithocholic acid 7-ketolithocholic acid after its intestinal absorption may be reduced in the liver to chenodeoxycholic acid or ursodeoxycholic acid. In the present study absorption of 7-ketolithocholic acid in jejunum, ileum, and colon was measured. When 7-ketolithocholic acid was perfused with a concentration of 0.025 mmol/l the absorption in the jejunum was 6.2 +/- 0.9 nmol/cmxh (mean +/- SD), in the ileum 8.1 +/- 0.2 nmol/cmxh, and in the colon 11.2 +/- 1.7 nmol/cmxh. The absorption of 7-ketolithocholic acid in jejunum, ileum, and colon was equal to the absorption of ursodeoxycholic and chenodeoxycholic acid. The equal absorption rates of 7-ketolithocholic, ursodeoxycholic, and chenodeoxycholic acid indicate, that substitution of the 7-hydroxyl group by the 7-keto group has no influence on the intestinal absorption of bile acids. The excellent colonic absorption of 7-ketolithocholic acid demonstrates, that not only the small intestine but also the colon contributes to the enterohepatic circulation of bile acids.     

Chenodeoxycholic and ursodeoxycholic acids alter motility and fluid transit in the canine ileum

We examined the effects of chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA) on fasting motility patterns and transit in ileocolonic loops of 5 dogs. Animals were prepared with isolated loops (40 cm ileum and 5 cm colon) which maintained neuromuscular continuity with the intact bowel through a bridge of tunica muscularis. Myoelectrical activity was recorded from multiple serosal, monopolar electrodes and muscle contractions recorded from serosal strain gauges; fluid transit was assessed by continuous perfusion (1.4 ml min-1) of solutions containing polyethylene glycol 4000 marker, with or without bile acids. Saline perfusion did not disturb the fasting cycle of motility and mean cycle length in unperfused (106 +/- 7 min) loop was the same as during perfusion of saline (108 +/- 9 min). Bile acids abolished interdigestive cycles in 11 of 12 experiments, fasting patterns returned 64-106 min after bile acid perfusion was stopped. The fasting pattern continued to cycle normally in the proximal small bowel during bile acid perfusion. CDCA (15 mM) stimulated the occurrence of propulsive contractions of long duration. Bile acids shortened transit time through the loops and altered the pattern of flow towards a more continuous, steady stream. These effects of bile acids on ileal motility, like those described previously in the colon, could play a role in bile acid diarrhea.     

Effect of L-tryptophan on fasting intestinal motility and intestinal transit time in the human

Since previous experiments in dogs suggested L-tryptophan to disturb the migrating motor complex (MMC) we set out to study its effects in man. In six healthy volunteers intraduodenal instillation of 50 mmol L-tryptophan did not disrupt the interdigestive motility pattern. In comparison to saline L-tryptophan caused a brief and local increase of motor activity in the upper small bowel. There was no change in small bowel transit time. The oral intake of 560 kcal liquid formula diet produced a typical digestive pattern for 160-209 min. The increase and the maximum of serum gastrin levels did not correspond to the changes of motor activity.     

Absorption and motility of the bypassed human ileum

The authors assessed absorption and motility of the human ileum after a prolonged period of disuse. In eight patients with ulcerative colitis, a manometric-catheter assembly was placed via the ileostomy into the unused portion of distal ileum two months after ileal pouch-anal anastomosis and temporary diverting loop ileostomy. The distal ileum was perfused at 5 ml/min with an isosmotic solution of either sodium chloride or ileal chyme diluted with sodium chloride for three hours before and three hours after a meal on two consecutive days. Absorption was measured, single and clustered pressure waves were identified and quantitated with the aid of a computer program, and a motility index was calculated. Mean absorption ± S.E.M. of both perfusates was poor on day 1 (–10±2 ml/25 cm × 30 min), and the meal induced no ileal motor response. By day 2, however, absorption of both perfusates was much improved (–1±2 ml/25 cm × 30 min; P<0.05), and the number of discrete clustered contractions and the motility index now clearly increased after the meal (2.6±0.6 vs. 7.2±1.0 clustered waves/hr; 7.5±0.5 vs. 9.7±0.2 motility units/30 min;P<0.05).The conclusion was that absorption and motility of the human ileum were impaired after two months of disuse, but that ileal absorption and motility improved one day after the introduction of isosmotic ileal perfusates.Supported in part by USPHS NIH Grants DK34988, DK18278 and DK07198, and the Mayo Foundation.     

Influence of myectomy,ileal valve,and ileal reservoir on the ecology of the ileum

Fecal bacteriology, fecal volatile fatty acids, and ileal mucosal morphology were studied in dogs after ileoanal anastomosis alone, ileoanal anastomosis and myectomy, ileoanal anastomosis and myectomy with ileoileal valve, and ileoanal anastomosis with duplicated (J) ileal reservoir. The ratio of anaerobes to aerobes was significantly less in stool from dogs which had undergone ileoanal anastomosis compared with each of the other three groups ( P <0.01). The numbers of streptococci and clostridia both were significantly less in stool from dogs with ileoanal anastomosis alone than in any other group. The concentrations of fecal acetic and propionic acids were significantly less in dogs with ileoanal anastomosis alone than in any other group ( P <0.05), but there were no significant differences in the concentrations of fecal butyric or valeric acids. The severity of mucosal inflammation and degree of villous atrophy were more marked in the ileum of J reservoirs ( P <0.01), and the percentage of stool retained after defecation was greater ( P <0.05) in dogs with J reservoirs than in any other group. Therefore, the use of myectomy resulted in significant changes in the ecology of the distal ileum although changes typical of pouchitis were seen only in dogs with J reservoirs.Read at the meeting of The American Society of Colon and Rectal Surgeons, Boston, Massachusetts, May 12 to 17, 1991.Supported in part by a grant from the Special Trustees Fund, University of Leeds.     

Effect of inhibitors on sodium and chloride transport in brush border vesicles from human jejunum and ileum

Brush border vesicles were isolated from surgically resected pieces of human jejunum and ileum using a Mg2+/EGTA precipitation method. When compared to the homogenate, the final membrane preparation contained alkaline phosphatase at a 14 times higher concentration and almost no (Na++K+)-stimulated adenosine triphosphatase. An Na+/H+ antiport could be demonstrated in the jejunum by imposing a pH gradient between the interior and the outside of the vesicles (pHinside 5.2, pHoutside 7.2). In the presence of amiloride or harmaline, Na+/H+ antiport was inhibited by 60 +/- 5% (p less than 0.05) or 65 +/- 5% (p less than 0.05), respectively. In vesicles of human ileum we found an Na+/H+ antiport and in contrast to the jejunum a Cl-/OH- antiport could be demonstrated by imposing a pH gradient (pHinside 5.2, pHoutside 7.2). Besides this double-exchange mechanism for sodium and chloride, a Na+/Cl- cotransport and a Cl- conductive pathway could be detected in ileal brush border vesicles. In the presence of the anion transport inhibitors, furosemide, SITS and DIDS activities of Cl-/OH- antiport and Na+/Cl- cotransport were suppressed by 30 +/- 5% (p less than 0.05), 35 +/- 5% (p less than 0.05) and 40 +/- 5% (p less than 0.05), respectively. We conclude that absorption of sodium and chloride in the absence of organic solutes is mediated through different transport mechanisms at the luminal plasma membrane, which are in part subject to regulation by sodium and chloride transport inhibitors.     

Villous motility: relationship to lymph flow and blood flow in the dog jejunum

Villous contraction frequency, lymph flow, blood flow, and arteriovenous oxygen difference were measured in dog jejunum. Venous pressure elevation and plasma dilution were used to increase capillary fluid filtration. Both perturbations produced concomitant increases in villous contraction frequency and lymph flow. A highly significant correlation (r = 0.83, p less than 0.001) was obtained between villous contraction frequency and lymph flow. This finding, coupled with the observation that stimulation of net fluid absorption increases villous contraction frequency, suggests that villous motility is increased by a myogenic response elicited by increments in interstitial fluid pressure. In another series of experiments local arterial pressure was reduced in 20-mmHg steps from 120 to 20 mmHg. Although blood flow fell proportionately to arterial pressure, villous contraction frequency and oxygen uptake were maintained at a normal level when arterial pressure was between 120 and 60 mmHg. Villous motility and oxygen consumption fell progressively as arterial pressure was reduced below 60 mmHg. This observation indicates that ischemia does not alter villous contraction frequency unless blood flow is reduced below the level necessary to maintain normal tissue oxygenation.     

Decreased fluid tolerance, accelerated transit, and abnormal motility of the human colon induced by oleic acid

To determine whether the presence of unabsorbed fat in the colon altered colonic motility, intraluminal pressures were recorded in the terminal ileum and proximal colon, and serial 1-min gamma camera scans were obtained while test solutions labeled with diethylenetetramine pentaacetic acid chelate of indium 111 were infused into the middle portion of the ascending colon. Seven subjects received a control solution, and 6 subjects received an emulsion of oleic acid (4.3 g/100 ml). Oleic acid accelerated colonic transit; isotope accumulated in the rectosigmoid faster in the first 120 min (4343 +/- 1175 cpm) than it did during control infusion (1236 +/- 348 cpm; p less than 0.01). Accelerated transit of oleate was accompanied by high amplitude (greater than 60 mmHg, range 60-95 mmHg), prolonged (greater than 10 s, range 10-48 s), propagated pressure waves; they originated near the ileocecal junction at a median frequency of 1.3 times/hour (mean 4.1, range 0.4-15.7). These were associated with a narrow image of the ascending colon on scintiscan and movement of 65.9% +/- 6.5% of counts from the ascending to transverse colon over the succeeding 4 min. A similar sequence was seen only once in 33 h of infusion with control solutions (p less than 0.01). Associated with these responses, the total volume of infusate tolerated before defecation was less with oleate than with control solutions (311 +/- 21 ml vs. 1049 +/- 71 ml; p less than 0.01). Long-chain fatty acids stimulated unusual motor patterns and reduced the reservoir function of the ascending colon; these effects may contribute to the diarrhea of patients with fat malabsorption.     

Ontogeny of procholecystokinin maturation in rat duodenum, jejunum, and ileum.

Expression and processing of procholecystokinin (proCCK) in rat intestine during development were examined using sequence-specific immunoassays, cleavage with processing-like enzymes, and chromatography. Fetal proCCK concentrations were similar in duodenum, jejunum, and ileum, but the maturation to CCK followed different courses: duodenal CCK increased from 14 pmol/g in the fetus to 86 pmol/g 4 days after birth and then declined to 17 pmol/g in the adult. In jejunum, CCK varied from 34 pmol/g in the fetus to 127 pmol/g at day 7, decreased to 54 pmol/g at day 21, and increased again to 93 pmol/g in the adult. Ileal CCK decreased from 20 pmol/g in the fetus to 10 pmol/g postnatally. Whereas duodenal proCCK after birth matured completely to carboxyamidated CCK, jejunoileal proCCK matured only partially. Chromatography showed an increase of tyrosine-sulfation and proteolytic processing of N-terminal sequences. At day 7 jejunal cholecystokinin octapeptide (CCK-8) constituted only a minute fraction of the carboxyamidated CCK, of which less than half was sulfated. However, in the adult jejunum, CCK-8 constituted a significant fraction, which was completely sulfated. It is concluded that the CCK gene is well expressed at propeptide level in the fetal small intestine. Postpartum maturation of proCCK, however, is late and differs in the three parts of the small intestine. The belated maturation supports the hypothesis that factors other than CCK regulate pancreatic growth in fetal and neonatal life.     

Effect of cholera toxin on the human jejunum.

In order to develop a model for secretory diarrhoea and to confirm the in vitro effects of cholera toxin in man in vivo the effect of intrajejunally administered cholera toxin was investigated in healthy volunteers. An intestinal perfusion technique with an occluding balloon proximal to the infusion site was used. The jejunum was perfused under steady state conditions with a plasma like electrolyte solution containing polyethylene glycol as a non-absorbable volume marker. After two control periods of one hour each, during which water was absorbed at a rate of 104 (14) (mean (SEM), n = 15) and 94 (15) ml/30 cm/h, respectively, three different doses of cholera toxin (6.25 micrograms, 12.5 micrograms, 25 micrograms) were administered by bolus into the lumen of the jejunum. Cholera toxin reduced absorption of water and electrolytes progressively over four hours and induced secretion in a dose dependent fashion. In the fourth hour net secretion amounted to 22 (23), 36 (24), and 88 (40) ml/30 cm/h (each n = five) with doses of 6.25, 12.5, and 25 micrograms cholera toxin, respectively. The movement of sodium, chloride, and bicarbonate paralleled water movement. Our results suggest that cholera toxin may serve as a secretory model in the human jejunum which might allow testing of new antisecretory agents.     

Effects of secretin and cholecystokinin on motor activity of human jejunum. A radiotelemetering study of jejunal motility during secretin and cholecystokinin intravenous infusion.

The effects of intravenous administration of secretin and cholecystokinin (CCK) on motility of the human jejunum were investigated with pressure-sensitive radiotelemetering capsules. Secretin inhibited and CCK stimulated the spontaneous motor activity of this part of the small intestine. Raising the dosages of the two hormones caused increasing effects. It seems likely, therefore, that both hormones play a role in the regulation of intestinal motility in man.     

Effect of propionibacteria supplementation on fecal bifidobacteria and segmental colonic transit time in healthy human subjects

BACKGROUND: Some strains of Propionibacterium have bifidogenic properties and enhance gut motility in the animal. However, they are not part of the indigenous fecal flora. This study was designed to assess the digestive survival of ingested propionibacteria, their bifidogenic properties, and the resulting changes in colonic transit time in healthy humans. METHODS: Eighteen subjects were given 5 . 10(10) CFU propionibacteria/day during 2 weeks. Fecal concentrations of propionibacteria and bifidobacteria were counted before (day -8, day -1), during (day 7, day 14), and after (day 21, day 28) the supplementation. Colonic transit time was measured before and at the end of the 1st week of supplementation. RESULTS: Basal counts of propionibacteria were less than 5 log CFU/ml stools. They increased in 15 subjects to (mean+/-1 standard deviation) 5.63+/-0.71 and 6.37+/-0.89 on day 7 (P < 0.01) and day 14 (P < 0.01) and returned to basal levels on day 21. Basal counts of bifidobacteria (mean, 7.94+/-0.71) increased to 8.39+/-0.97 on day 7, 8.36+/-0.86 on day 14, and 8.70+/-0.95 on day 21 (P < 0.05 from mean basal count) and returned to pretreatment levels on day 28 (7.88+/-1.38). Mean counts of propionibacteria during supplementation and bifidobacteria levels on day 14 were significantly correlated (P = 0.01). Transit time did not change in the right colon (17.4+/-8.1 h versus 17.3+/-8.3 h) or in the rectosigmoid area(12.8+/-8.5 versus 13.3+/-0.2 h); left colon transit was significantly slowed (7.0+/-5.0 h versus 11.9+/-9.4 h; P < 0.05). CONCLUSIONS: Part of the ingested propionibacteria were able to survive the digestive transit. This supplementation was associated with changes in segmental colonic motility, yet the mechanisms involved in these changes remain unknown.     

Study of the effect of ileal distension on the motor activity of the jejunum, and of jejunal distension on the motor activity of the ileum

BACKGROUND/AIMS: The effect of ileal distension on the jejunal motor activity and ofjejunal distension on the ileal motility have been poorly addressed in the literature. We investigated the hypothesis that distension of either ileum or jejunum would affect the motile activity of the other. METHODOLOGY: Response of jejunal pressure to ileal balloon distension and of ileal pressure to jejunal distension in increments of 2 mL of normal saline were recorded in 18 dogs. The test was performed after individual local anesthetization of the ileum and jejunum and was repeated using saline instead of lidocaine. RESULTS: Ileal distension with 2, 4, and 6mL of saline produced no jejunal pressure response (p >0.05), while 8- and up to 12-mL distension effected jejunal pressure decrease (p<0.05). Jejunal distension up to 6mL did not change ileal pressure (p>0.05); distension with 8, 10, and 12 mL reduced it (p<0.05). Jejunal or ileal pressure responses were maintained as long as ileal or jejunal distension was continued. Distension of the anesthetized ileum or jejunum did not produce significant pressure changes in either. CONCLUSIONS: Jejunal or ileal pressure decrease and presumably hypotonia upon large-volume ileal or jejunal, respectively, distension postulate reflex relationship which we call 'ileal-jejunal and jejuno-ileal inhibitory reflex'. These reflexes appear to regulate chyme flow in small intestine by creating a balance of chyme delivery between the jejunum and ileum. Reflex derangement in neurogenic and myogenic diseases may result in gastrointestinal disorders, a point that needs to be investigated.