Prolonged ambulatory duodeno-jejunal manometry in humans: normal values and gender effect

OBJECTIVE: The aim of this study was to provide a detailed comparison of motor activity in the duodenum and jejunum and between men and women studied by prolonged ambulatory manometry. METHODS: Thirty healthy volunteers (17 males) underwent prolonged ambulatory recording of duodeno-jejunal motility using a catheter with five built-in strain-gauge transducers (two duodenal and three jejunal). Manometric data was obtained during an extended period of fasting, the postprandial period and during sleep. RESULTS: There was a wide range of durations of the migrating motor complex (MMC), but at least one phase III was detected during 6 h of fasting, or 6 h of sleep in each subject (0.52+/-0.04 phase III/hour during fasting vs 0.59+/-0.04 during sleep, p=0.1). There was marked variation in the duration and pattern of phase III. Postprandially, frequency of contractions and motility index were maximal in the first 2 h after the meal, in both the duodenum and jejunum. There were no substantive differences between males and females or between the duodenum and jejunum. CONCLUSION: We conclude that upper small bowel motility is little affected by gender or segment.     

Intestinal motility after massive small bowel resection

To evaluate intestinal motility after 80% massive distal small bowel resection (MSBR), we continuously monitored interdigestive and postprandial bowel motility using bipolar electrodes and/or contractile strain gage force transducers in conscious beagle dogs before, and at 0-4 weeks and 8-13 months after the surgery. Fasting duodenal migrating myoelectric (or motor) complexes (MMCs) occurred at longer intervals in the short-term after 80% MSBR than in controls, and were simulated in long-term that in controls. MMCs arising from the duodenum were often migrated to the proximal jejunum, the jejunum above the anastomosis, and to the terminal ileum beyond the anastomosis. The velocity of duodenal MMC propagation was slowed in every intestinal segment in the short-term, and had not recovered even long after the operation. The duration of the postprandial period without duodenal MMCs was prolonged significantly in the short-term, and still remained longer in the long-term than in controls. These findings suggest that changes in gut motility after MSBR tend to compensate for the shorter intestine and maintain small bowel absorption early postoperatively, and adaptations of motility would occur over the long-term to increased intestinal absorption.     

Absorption of simple nutrients from the in vivo neurally isolated canine jejunum and ileum

BACKGROUND: The effects of intestinal transplantation on enteric absorptive function are not well understood. Our aim was to determine the effects of in situ isolation of the jejunoileum, a large animal model of jejunoileal autotransplantation, on absorption of simple nutrients from the jejunum and ileum separately. METHODS: Four groups of dogs were prepared with modified Thiry-Vella loops: group 1, neurally intact jejunum; group 2, neurally isolated jejunum; group 3, neurally intact ileum; and group 4, neurally isolated ileum. Intestinal loops were perfused with five different isosmolar solutions of NaCl alone, 30 mmol/L glucose, 2.5 mmol/L glycine, 2.5 mmol/L phenylalanine, and 5 mmol/L oleic acid at 1 to 2 weeks and 8 to 9 weeks after operation. RESULTS: Net absorption of water and electrolytes, glucose, glycine, phenylalanine, and oleic acid were not different statistically between neurally intact and neurally isolated intestinal loops at either time point. Ileal loops absorbed more than jejunal loops. CONCLUSIONS: Absorption of simple nutrients from the canine jejunum and ileum is not altered by this model of intestinal autotransplantation. These observations suggest that the extrinsic denervation that accompanies intestinal transplantation does not affect the transport systems for glucose, glycine, phenylalanine, or oleic acid.     

Varicosities of the paravertebral plexus of veins associated with nocturnal spinal pain as imaged by magnetic resonance venography: a brief report

BACKGROUND: Non-cholinergic non-adrenergic neural mechanisms involving nerves containing NO have been shown to modulate smooth muscle in the gastrointestinal tract, and it has been suggested that release from tonic NO inhibition may be important in the regulation of cyclical fasting small intestinal motility. AIMS: To evaluate the role of NO mechanisms in the regulation of fasting small intestinal motor activity in humans using a specific NO synthase inhibitor, NG-monomethyl-L-arginine ( L-NMMA). METHODS: In seven healthy male volunteers, duodenal and jejunal pressures were measured for four hours with a nine lumen manometric catheter. Volunteers attended on four separate days on which they received an intravenous infusion either saline or L-NMMA (0.5, 2, or 4 mg/kg/h) in random order. Intravenous infusions began 10 minutes after completion of phase III of the migrating motor complex (MMC). RESULTS: The first episode of phase III activity occurred earlier after infusion of 2 and 4 mg/kg/h L-NMMA than after infusion of 0.5 mg/kg/h L-NMMA or saline (mean (95% confidence interval) 52 (36-68) and 57 (18-97) v 116 (69-193) and 145 (64-226) minutes respectively) with a resultant MMC cycle length of 82 (59-105) and 86 (46-126) v 132 (49-198) and 169 (98-240) minutes respectively. The total number of phase III activities during the four hour recording was increased (p<0.05) by L-NMMA at a dose of 4 mg/kg/h (2 (1-3)) but not at 2 mg/kg/h (1.5 (1-2)) or 0.5 mg/kg/h (1.3 (1-2)) compared with saline (1.3 (0.6-2)). L-NMMA had no effect on the duration, velocity, number of contractions per minute, length of migration, or site of origin of phase III of the MMC. The duration of phase I activity was shorter (p<0.05) with 4 mg/kg/h L-NMMA than with saline (12 (1-23) v 31 (19-44) minutes). CONCLUSIONS: These observations suggest that NO mechanisms play a role in the regulation of fasting small intestinal motor activity in humans.     

On the synthesis of platelet-activating factor via acetylation of 1-alkyl-sn-glycero-3-phosphocholine. Formation of structural isomer of PAF in the presence of bases

Duodenal motor activity is incompletely understood. The purpose of this study was to define the contractile patterns of the duodenum that occur in response to rate controlled injection of various solutions. In nine healthy volunteers we placed a six channel perfused catheter, and recorded pressure activity in the antrum, pylorus and duodenum. Volumes of 10 and 20 mL of 0.9% NaCl, 100 mM HCl (pH 1), 5% NaCl (1711 mOsm/kg), human bile and iso-osmolar sodium oleate were randomly injected into the duodenum at 20 ml/min, starting 15 min after phase III migratory motor complex (MMC). A 20 mL bolus of each solution caused more activity (P < 0.05) than a 10 mL bolus, but the motor pattern was similar. The control, 0.9% NaCl, produced occasional pressure waves, whereas bile and sodium oleate induced more (P < 0.05) activity which consisted of low amplitude, isolated or clusters (2-4 cycle/min) of non-propagating pressure waves that occurred at random sites. In three subjects, oleate produced isolated pyloric phasic contractions. In contrast, HCl and 5% NaCl induced high amplitude pressure waves that were seen either at a single channel or at multiple channels, occurring simultaneously. The motility index was also greater (P < 0.05) than that induced by other solutions. Additionally, within 2 min of infusion, a phase III MMC like pattern was observed in five of the nine subjects who received HCl and three of the nine who received 5% NaCl. A non-nutrient iso-osmolar solution induced occasional motor activity. HCl and hyperosmolar solutions induced more frequent and large amplitude, segmental contractions whereas lipid and bile induced fewer and smaller amplitude contractions. The volume, the pH, the osmolar and the nutrient make up of the infusate may each influence the duodenal motor responses.     

Role of bile acids in duodenal migrating motor complexes in dogs

Previous studies have suggested that enterohepatic circulation of bile acids is essential for regular cycling of duodenal migrating motor complexes (MMCs). The present study was an attempt to clarify the role of bile acids in the enterohepatic circulation system in initiating duodenal MMCs. Seven dogs underwent total external biliary diversion that resulted in the loss of MMCs originating from the duodenum. Sodium ursodeoxycholate (6 mg/kg/hr) was then given either through the portal vein or a peripheral vein, and motility of the gastrointestinal tract was serially recorded. When sodium ursodeoxycholate was given either through the portal vein or a peripheral vein during external biliary diversion, duodenal MMCs restarted. The cyclic change in plasma motilin levels during an MMC cycle as induced by sodium ursodeoxycholate was almost the same as in a normal MMC cycle. Total bile acid concentration in the portal vein changed cyclically with MMC cycles when bile flow was intact but did not change cyclically with MMC cycles restarted by intravenous bile salt infusion. Bile acid stimulation of putative receptors existing between the portal vein and intrahepatic bile ducts may be involved in initiating normal duodenal MMC cycles.     

Gastric antrectomy with selective gastric vagotomy does not influence gallbladder motility during interdigestive and postprandial periods

Fasting gastrointestinal motility and gallbladder motility during the interdigestive state and in the postprandial period was studied in eight patients who were operated for ulcer disease with an antrectomy and selective gastric vagotomy. Nocturnal motility recording revealed all three phases of the migrating motor complex (MMC) in all but one patient, where no phase III activity was recorded. In the rest of the patients 3-10 events with phase III activity were recorded. At scintigraphy ([75Se]HCAT) a cyclic gallbladder filling and emptying in relation to the MMC cycle was found. Episodes with emptying were confined to phase II and a total of 13 episodes with a median duration of 25 min (range 10-70 min) were observed. A median of 10.7% (6.1-17.7%) of the gallbladder contents was emptied. In a control group of eight healthy young men the values were 13.5 min (9-36 min) and 6.9% (3.7-31.1%), respectively. These differences were not significant. During the postprandial period, a lag period in gallbladder emptying of median 15 min (5-20 min) was observed when food ingestion took place during phase I of the MMC. Thereafter a gradual emptying occurred with a rate of 0.95% min (0.71-1.15%/min). In a control group of healthy young males, the lag period was 13.5 min (9-22.5 min) and the emptying rate 0.61%/min (0.08-0.77%/min). When food ingestion occurred during phase II of the MMC, the lag period of gallbladder emptying in the patient group was median 0 min (0-5 min) and the emptying rate was 0.77%/min (0.33-0.86%/min). The values in the control group were 0 min (-9 to 13.5 min) and 0.76%/min (0.54-2.25%/min), respectively. These differences between the patients and controls were not significant. In conclusion, antrectomy and selective gastric vagotomy do not influence fasting gastrointestinal motility or gallbladder motility during the interdigestive state or in the postprandial period.     

Development of a shortened version of the Breathing Problems Questionnaire suitable for use in a pulmonary rehabilitation clinic: a purpose-specific, disease-specific questionnaire

MMC-related retroperistalsis is a cyclical phenomenon in the duodenum linked to phase III. The aim of this study was to elucidate the direction of propagation of juxtapyloric duodenal pressure waves in the postprandial state in healthy humans and to compare with the contractions in the interdigestive phase II. Antroduodenal manometry was performed in 11 healthy subjects. Individual pressure waves propagating along a 6-cm duodenal segment were analysed with respect to the proportions of antegrade and retrograde propagation in the four duodenal subsegments (D1-D2) to (D4-D5), each subsegment being 15 mm. A test meal was given 30 min after a phase III had passed and motility recording continued for 60 min after the meal. During both the first and the second 30-min period of postprandial recording the proportion of retrograde pressure waves was larger just distal to the pylorus, (D1-D2), 40% (23-68) and 50% (23-68), respectively, compared to the distal part, (D4-D5), of the duodenal segment, 29% (12-30) and 10% (10-24), respectively (P < 0.05 and 0.01). In contrast, during late phase II of the interdigestive state antegrade pressure waves predominated in all four duodenal subsegments. We conclude that in the postprandial state a high proportion of the duodenal pressure waves (40-50%) is retrograde in the immediate juxtapyloric area while antegrade contractions predominate at a distance 5-6 cm distal to the pylorus. These manometric data together with recent observations of postprandial transpyloric liquid flow, indicate that retrograde duodenogastric propelling of contents may be an important determinant for the gastric emptying rate.     

Dystonia

The need for extrinsic neural input to the upper gut in regulation/control of cyclic interdigestive motility and release of motilin remains a topic of controversy. Our aim was to determine whether extrinsic denervation of the upper gut disrupts cyclic release of motilin in relation to the migrating motor complex. Ten dogs underwent transection of all extrinsic innervation and enteric neural input to the stomach, small intestine, colon, pancreas, and liver while enteric neural continuity within this multivisceral complex was maintained. A cyclic pattern of motility occurred during fasting in all dogs in the small bowel (period = 100 +/- 3 min, mean +/- standard error of the mean) and in 8 of 10 dogs in the stomach (period = 98 +/- 4 min). Gastric cycles were temporally coordinated with small bowel cycles. Plasma motilin concentrations cycled temporally with the motility pattern with the greatest concentrations occurring during gastroduodenal phase III-like activity. Exogenous motilin induced a burst of gastric contractions and a premature migrating motor complex in all dogs. Oral meals disrupted cyclic motility and cyclic changes in plasma motilin. Extrinsic innervation to the upper gut is not necessary for cyclic motor activity, for coordinated cyclic release of motilin, or to initiate a premature migrating motor complex-like response to motilin. Central nervous system input (afferent, efferent) is not necessary for cyclic interdigestive activity or cyclic release of motilin.     

Functional changes in nonadrenergic, noncholinergic inhibitory neurons in ileal circular smooth muscle after small bowel transplantation in rats

This experiment was designed to determine mechanisms of change in nonadrenergic, noncholinergic (NANC) inhibitory neurons in the ileum after small bowel transplantation (SBT) in the rat and whether nitric oxide (NO) serves as an important NANC inhibitory neurotransmitter in the rat ileum. Eight groups of rats (N > or =8 rats/group) were studied: neurally intact unoperated controls; rats one week after anesthesia and sham celiotomy; and separate groups one and eight weeks after either 40 min of cold ischemia of the jejunoileum, combined jejunal and ileal intestinal transection/reanastomosis, or orthotopic SBT of the entire jejunoileum. Contractile activity was evaluated in full-thickness ileal circular muscle strips under isometric conditions. Spontaneous activity did not differ among groups. In all groups, exogenous NO, NG-monomethyl-L-arginine (L-NMMA, an NO synthase inhibitor), and methylene blue (soluble guanylate cyclase inhibitor) had no effect on spontaneous activity, while 8-bromocyclic guanosine monophosphate (8Br-cGMP) inhibited contractile activity in all groups. Low frequency (2-10 Hz) electrical field stimulation (EFS) inhibited contractile activity only in control and SBT groups; L-NMMA and methylene blue did not alter the response to EFS in any group. These results suggest that each aspect of the SBT procedure, ischemia/reperfusion injury, disruption of enteric neural continuity by intestinal transection, and extrinsic denervation, alter function of enteric ileal inhibitory neurons separately early (one week) after operation. NO, a known inhibitory neurotransmitter in other gut regions, does not affect ileal circular muscle in neurally intact tissue nor mediate functional changes in inhibitory nerve function nor smooth muscle contractility after SBT.     

Response of the human intestine to high volume infusion

The motor patterns and luminal capacity of the human intestine should affect symptoms and resorption during pathological, massive small intestinal flow. Little is known of human intestinal motility in this situation. This study aimed at mimicking secretory diarrhoea (experimentally) in healthy volunteers by intrajejunal infusion of a non-absorbable iso-osmotic solution at 20 ml/min. During the infusion intraluminal jejunal pressures and small intestinal transit times were measured. The infusion initially caused jejunal contractile activity similar to that of the fed state but this was replaced by discrete clusters of contractions (DCCs) after 29.1 ((SEM) 8.2) minutes. DCCs each lasted 38 ((SEM) 0.8 seconds) and were associated with colicky abdominal discomfort. Later, after 1400-1800 ml had been infused, distal jejunal pressure waves fell to 10 mm Hg or less. Frequent fasting DCCs predicted earlier onset and more frequent DCCs during the infusion. Thus, the rate and volume of flow during simulated secretory diarrhoea determine the pattern of the small bowel pressure profile; eventually, a volume load is reached in which the small bowel acts as a poorly segmenting conduit resulting in very fast transit rates.     

Determination of tetracycline residues in animal tissues by liquid chromatography

BACKGROUND: Sufficient intraluminal concentrations of 5-aminosalicylic acid (ASA) within inflamed regions of the intestine are required for therapeutic efficacy in inflammatory bowel disease. Various oral delayed release preparations have been developed to ensure that 5-ASA is set free in those parts of the gut, which are most frequently affected. However, resulting intraluminal concentrations within the small bowel are unknown. Therefore, we determined and compared 5-ASA release within different segments of the small bowel from an Eudragit L coated 5-ASA preparation (Salofalk) and from an ethylcellulose coated microsphere preparation (Pentasa). METHODS: Twelve healthy subjects were intubated with an oro-ileal multilumen-tube for marker perfusion, duodenal, jejunal and ileal aspiration of chyme and intestinal manometry. Each subject received 500 mg 5-ASA (Salofalk, n = 6, or Pentasa, n = 6) together with a semiliquid test meal. Intestinal aspirates, blood and urine samples were obtained in regular intervals for 7 to 10 hours and were analysed for 5-ASA and its main metabolite acetyl-5-ASA by HPLC. RESULTS: With Salofalk, gastric emptying of 5-ASA did not take place in the digestive, but in the subsequent interdigestive period. Luminal delivery of 5-ASA and acetyl-5-ASA increased from the duodenum (3% of dose) to the ileum (30% of dose). 10% of the dose administered were excreted in urine and about 90% reached the colon unreleased or solubilised. By contrast, with Pentasa, 5-ASA was delivered to the duodenum together with the test meal and released continuously throughout the small intestine (about 20% of dose solubilised at each intestinal site). Only 3.5% of the dose administered were excreted in urine. Deliver of 5-ASA to the colon was equal to Salofalk. CONCLUSIONS: From both preparations, considerable amounts of 5-ASA are released during small intestinal transit thus explaining therapeutic efficacy in small intestinal Crohn's disease. Because of specific release patterns, Salofalk may be of use especially in terminal ileal disease, where as patients with extensive small intestinal disease including the proximal small intestine might benefit from Pentasa.     

Global control of meiotic recombination genes by Schizosaccharomyces pombe rec16 (rep1)

1. The influence of circulating 5-hydroxytryptamine (serotonin) on small intestinal motility was investigated in healthy volunteers. 2. Small intestinal motility was studied by means of a constantly perfused multi-channel manometry tube, connected to a computer system. 3. Intravenous infusions of either 5-hydroxytryptamine at increasing doses or saline were given over a period of 4 h. 4. 5-Hydroxytryptamine infusion dose-dependently increased plasma 5-hydroxytryptamine from approximately 2 to 10 and 25 nmol/l respectively, as well as urinary excretions of 5-hydroxytryptamine and 5-hydroxyindole acetic acid, a major 5-hydroxytryptamine metabolite. 5. The number of phase III of the migrating motor complex originating in the small intestine was dose-dependently increased by 5-hydroxytryptamine, and found to correlate to the plasma concentration of 5-hydroxytryptamine. The fraction of phase III also increased at the expense of phase II activity. In addition, 5-hydroxytryptamine increased the motility index, propagation velocity of phase III activity and the amplitude of contractions during phase III. 6. Whereas the low dose of 5-hydroxytryptamine (15 nmol.min-1.kg-1) had no haemodynamic effects, an increase in heart rate by approximately 20 beats/min, without change in blood pressure, was observed at the higher dose (60 nmol.min-1.kg-1). Respiratory parameters did not change during infusion of 5-hydroxytrytamine at either dose. 7. In conclusion, elevation of circulating 5-hydroxytryptamine by intravenous infusion results in more frequent and faster propagating migrating motor complexes in the human small intestine during the inter-digestive period.     

Manometry of the upper intestinal tract in patients with systemic sclerosis: a prospective study

OBJECTIVE: To assess both the prevalence and the characteristics of motor disorders of the small bowel in patients with systemic sclerosis (SSc) and to investigate for an association between clinical manifestations in the upper intestinal tract, capillaroscopic features, esophageal motor impairment, and manometric evidence of motor disturbances. METHODS: Fasting and postprandial motor activity of the upper intestinal tract was studied in 17 consecutive patients with SSc (6 with and 11 without clinical manifestations of small bowel involvement) and 17 age- and sex-matched healthy control subjects. RESULTS: The prevalence of manometric evidence of intestinal involvement was as high as 88% in the SSc patients; normal motor activity was present in only 2 patients. The median values for duodenal and jejunal interdigestive phase III migrating motor complex duration, amplitude, and velocity and the postprandial motility index were therefore lower in SSc patients compared with controls. Our manometric findings indicated that there are both neuropathic and myopathic stages of upper intestinal tract dysfunction in SSc. Furthermore, no association could be found between the severity of the intestinal manometric abnormalities and clinical presentation, SSc subsets, disease score, capillaroscopic findings, or esophageal manometric impairment. CONCLUSION: We suggest that manometry of the upper intestinal tract may be useful in SSc patients with clinical manifestations in the small bowel (i.e., malabsorption syndrome or pseudoobstruction) in that it can be used to accurately evaluate both the nature and the severity of motor disturbances. Furthermore, this procedure can be used to assist in the selection of patients who may require octreotide therapy.     

Duodenum as a immediate brake to gastric outflow: a videofluoroscopic and manometric assessment

BACKGROUND & AIMS: Duodenal infusion of HCl or lipid delays gastric emptying. The aim of this study was to assess whether this delay was in part caused by mechanical activity of the duodenum. METHODS: Synchronized videofluoroscopy and manometry was used in 8 volunteers (5 men and 3 women) to examine contractile and flow patterns during duodenal infusion of 0.9% NaCl, HCl, 5% NaCl, bile, and sodium oleate, each mixed with 20% (wt/vol) barium sulfate. RESULTS: Within 15-30 seconds of infusion, HCl and 5% NaCl induced frequent large-amplitude contractions greater tha those induced by 0.9% NaCl. Initially, there was rapid dispersion of HCl followed by prolonged, tonic occlusion of the duodenum. The duodenal diameter decreased compared with that observed during 0.9% NaCl or oleate infusion. In contrast, after infusion of oleate or bile, duodenal diameter increased and there were fewer, smaller-amplitude, nonpropagating contractions with prolonged retention of solutions. Barium (20%; wt/vol) did not influence the motility index of any solution. CONCLUSIONS: HCl and 5% NaCl may restrict gastric outflow by inducing tonic occlusion of the duodenum, whereas bile and lipid may delay clearance by decreasing duodenal tone and contractility. Thus, the duodenum may serve as an immediate brake to gastric outflow either by delaying clearance or by offering rapid tonic resistance.     

Electromyographic studies on gastric and intestinal motor function following pylorus preserving gastrectomy with jejunal interposition in dogs (author's transl)

The gastric and intestinal motor function following pylorus preserving gastrectomy with jejunal interposition were studied electromyographically in dogs. The action potentials were recorded from the interposed jejunal segment, the preserving pylorus and the duodenum before and after insertion of warm water. Studies were made on the frequency, the propagation velocity of the spike-bursts in the portions mentioned above, and the incidence of the spike-bursts which propagated from the distal porition of the interposed jejunal segment to the preserving pylorus, and from the preserving pylorus to the proximal portion of the duodenum. The results obtained are as follows: 1) The frequency of the spike-bursts found in the interposed jejunal segment, the preserving pylorus, and the duodenum showed a remarkable increase after insertion of warm water. 2) The propagation velocity of the spike-bursts in the interposed jejunal segment, the preserving pylorus, and the duodenum were accelerated after insertion of warm water. 3) There were observed a moderate increase in the incidence of the spike-bursts which propagated from the distal portion of the interposed jejunal segment to the preserving pylorus, and from the preserving pylorus to the proximal portion of the duodenum after insertion of warm water. These findings suggested that the motor function of the interposed jejunal segment, that of the preserving pylorus, and that of the duodenum after pylorus preserving gastrectomy with jejunal interposition might be kept not yet injured enough to transport the contents from the interposed jejunal segment into the duodenum.     

Effect of cisapride and renzapride on gastrointestinal motility and plasma motilin concentration in dogs

The effects of cisapride and renzapride (BRL 24924), on plasma concentration of motilin and gastroduodenal motility were studied in seven dogs with implanted force transducers in the antrum and duodenum. In the interdigestive state, the i.v. administration of cisapride (5 mg) or renzapride (5 mg) administered in phase I resulted in a prompt and marked increase in plasma motilin concentration and in gastroduodenal motility. Mean plasma motilin levels during the first 30 min after cisapride and after renzapride injection were 85.0 +/- 6.5 (+/- S.E.) and 96.1 +/- 6.3 pM., respectively. These values were significantly greater (P < .001) than those for the corresponding time period of the control cycle, 52.2 +/- 5.6 and 57.4 +/- 5.3 pM (mean phase III level, 120 +/- 8.1 pM), respectively. The increases in the motilin level after cisapride or renzapride coincided with significant increases in contractile activities of the antrum to 43.2 +/- 5.3% and 44.9 +/- 4.6% and of the duodenum to 28.4 +/- 3.1% and 34.2 +/- 2.2% of phase III activity (100%) from that in the corresponding control period, 0.7 +/- 0.4% and 0.2 +/- 0.1%, respectively. The changes in both plasma motilin and motility in response to the two drugs were abolished completely by the i.v. administration of atropine. The drugs also enhanced the meal-induced contractile activities of the antrum as well as the duodenum but failed to influence the postprandial plasma motilin concentration. We conclude that cisapride and renzapride have similar effects on plasma motilin and gastroduodenal motility: 1) the two drugs increase plasma motilin levels and stimulate gastroduodenal motility in the interdigestive state, and 2) in the digestive state, both drugs enhance motility without influencing the plasma motilin levels.     

Nocturnal antral pH rises are related to duodenal phase III retroperistalsis

The mechanisms behind nocturnal rises of gastric pH are unknown. We have analyzed the relation between interdigestive duodenal peristalsis and nocturnal pH in the gastric antrum. Simultaneous recording of antroduodenal pressures and intragastric pH was performed in 11 healthy subjects (six men, five women) overnight for 8 hr, using a catheter with seven pressure recording points and an antral glass pH electrode. Three pressure recording sites were closely spaced in the descending duodenum. Altogether 46 phase III activities were recorded. A retroperistaltic sequence in the last part of phase III was observed in 31 phase III activities (67.4%), while 15 phase III activities lacked retroperistalsis. All subjects had retroperistalsis in at least one phase III at night with a median of 60% (52-100%) (interquartile range). The duration of the whole phase III was 5.1 (3.1-7.0) min, whereas the duration of the retroperistaltic period was 2.0 (1.5-3.2) min, corresponding to 45% (23-64%) of the duration of phase III. The peak of antral pH occurred 7.4 (6.0-13.0) min from the start of the phase III in the duodenum and and the rise in pH lasted for 8.0 (4.8-12.0) min. Measurement of pH for a period of 10 min before and after phase III, demonstrated an increase in median pH from 1.2 (1.1-1.9) to 3.2 (1.6-4.7), respectively (P < 0.001). Phase III activities without duodenal retroperistalsis were not followed by a significant antral pH change (median 1.7 vs 1.8 before and after phase III, respectively). Increases of pH unrelated to phase III were uncommon, only 1.0 (1.0-2.2) events per night were observed and lasted for a short period of time, 2.1 (0.5-3.2) min. The results indicate that the cyclic rise in antral pH at night is due to a physiological duodenogastric reflux, caused by duodenal retroperistalsis in phase III. This reflux may play a role in protection of the antral mucosa.     

Sympathetic and baroreceptor reflex function in neurally mediated syncope evoked by tilt

The pathophysiology of neurally mediated syncope is poorly understood. It has been widely assumed that excessive sympathetic activation in a setting of left ventricular hypovolemia stimulates ventricular afferents that trigger hypotension and bradycardia. We tested this hypothesis by determining if excessive sympathetic activation precedes development of neurally mediated syncope, and if this correlates with alterations in baroreflex function. We studied the changes in intraarterial blood pressure (BP), heart rate (HR), central venous pressure (CVP), muscle sympathetic nerve activity (MSNA), and plasma catecholamines evoked by upright tilt in recurrent neurally mediated syncope patients (SYN, 5+/-1 episodes/mo, n = 14), age- and sex-matched controls (CON, n = 23), and in healthy subjects who consistently experienced syncope during tilt (FS+, n = 20). Baroreflex responses were evaluated from changes in HR, BP, and MSNA that were obtained after infusions of phenylephrine and sodium nitroprusside. Compared to CON, patients with SYN had blunted increases in MSNA at low tilt levels, followed by a progressive decrease and ultimately complete disappearance of MSNA with syncope. SYN patients also had attenuation of norepinephrine increases and lower baroreflex slope sensitivity, both during tilt and after pharmacologic testing. FS+ subjects had the largest decrease in CVP with tilt and had significant increases in MSNA and heart rate baroreflex slopes. These data challenge the view that excessive generalized sympathetic activation is the precursor of the hemodynamic abnormality underlying recurrent neurally mediated syncope.     

Cardiac-specific overexpression of angiotensin II AT2 receptor causes attenuated response to AT1 receptor-mediated pressor and chronotropic effects

BACKGROUND & AIMS: The gastroduodenal epithelium is protected from acid-peptic damage, in part, by its ability to secrete bicarbonate. Patients with duodenal ulcer disease have impaired proximal duodenal mucosal bicarbonate secretion. We have shown in vitro that histamine inhibits prostaglandin-stimulated bicarbonate secretion in rabbit duodenal mucosa via histamine H2 receptors and enteric nerves. In this study we examined whether the proulcerogenic compounds aspirin or ethanol regulate duodenal bicarbonate secretion and the involvement of histamine. METHODS: Bicarbonate secretion by rabbit proximal duodenal mucosa was examined in vitro in Ussing chambers. RESULTS: Aspirin and ethanol decreased basal and prostaglandin-stimulated bicarbonate secretion; the latter effect was specific for prostaglandin. The inhibitory effects of the two ulcerogenic compounds were at least additive. Ranitidine and tetrodotoxin abolished the inhibitory effects on stimulated, but not basal, secretion. Aspirin and ethanol also induced release of duodenal histamine. CONCLUSIONS: Aspirin and ethanol act by two distinct pathways to impair duodenal bicarbonate secretion. Both agents inhibit basal secretion via a histamine-independent and neurally independent pathway while they inhibit prostaglandin E2-stimulated secretion via histamine release, likely from mast cells, and actions on enteric nerves. Our findings may be of relevance to the understanding and potential treatment of nonsteroidal anti-inflammatory drug-associated mucosal injury.