Functional relationships between cricopharyngeal sphincter and oesophageal body in response to graded intraluminal distension.

Responses of the cricopharyngeal sphincter to graded intraluminal distension were studied in order to determine its response threshold and to define the functional relationship between the sphincter and oesophageal body. Nine normal subjects underwent manometric study using a multilumen tube with an attached inflatable balloon sited 10 cm below the sphincter. Sphincteric and oesophageal motor responses to six graded balloon inflations were recorded in each subject. The sphincter responded to distension with increasing rise in pressure, from a median value of 42.5 mmHg at lowest levels of distension to 95 mmHg at maximal tolerated distension. Non-swallow related contractile activity was stimulated in the oesophageal body proximal to the distension and increased in quantity as inflation progressed. Distal propagation of this secondary activity was progressively inhibited with increasing distension. These interrelated changes thus show the normal upper oesophageal clearance responses to intraluminal distension. It is suggested that their more widespread application, in addition to standard manometric techniques, might provide a more rational evaluation of those patients suspected to have impaired oesophageal clearance, but in whom standard manometry is non-diagnostic.     

Motor responses of the small intestine to intraluminal distension in normal volunteers and a patient with visceral neuropathy.

The motor responses of the small intestine to intraluminal distension were studied proximal and distal to an inflatable balloon in 13 normal volunteers. During fasting, distension rapidly induced a persistent localised inhibition of distal contractile activity with a small proximal increase. Proximally, phase III activity was unaffected during distension but its propagation across and appearance below the balloon was inhibited. Upon deflating the balloon a normal motor pattern rapidly returned. Similar changes were observed during distension in the fed state. The changes in the motor pattern resemble those of the intrinsically mediated 'peristaltic reflex', studied in animals, and suggest that in man the response to balloon distension may also be mediated through an intrinsic mechanism. A patient with a visceral neuropathy, studied in a similar manner, had no inhibition of distal motor activity during distension, suggesting a functional defect of the enteric nerves. Further observations of the motor responses to distension in similar patients seem indicated to determine the usefulness of this technique for evaluating enteric nervous system function when an abnormality is suspected.     

Intraluminal pH and oesophageal motility in patients with gastro-oesophageal reflux

The effect of intraluminal pH on motor activity of the lower oesophageal body was studied in patients with pathological gastro-oesophageal reflux. Liquid boluses with a pH range of 6.98-1.1, infused in the distal oesophagus of 21 patients during manometric recording of motor activity, elicited either secondary peristalsis or simultaneous contractions. Acid pH did not affect the threshold of distension required to elicit secondary peristalsis. Oesophageal responses to volumes of instillate did not differ in patients with normal and abnormal acid clearing test, nor in patients with a negative and positive acid perfusion test.     

Studies of the oesophageal clearance responses to intraluminal acid.

Contraction of the upper oesophageal sphincter combined with secondary peristalsis clears the oesophagus of refluxed gastric contents and protects the trachea, but the nature of these reflex stimuli remains controversial. Secondary peristaltic and sphincteric responses were measured during intraluminal infusion of 0.1 N hydrochloric acid and equiosmolar saline solutions in seven normal volunteers. Responses to a single volume infused at varying sites in the oesophagus and to progressively increasing volumes of test solution were measured. In addition oesophageal responses to similar degrees of distension induced by inflation of an intraluminal balloon were also recorded. The sphincteric responses to both stimuli were similar, decreasing in value with distance from the sphincter from values of 70 (68-85) mmHg (median (range] for HCl; and 70 (55-85) mmHg for NaCl at 5 cm below the sphincter to 40 (30-60) mmHg for both HCl and NaCl at 20 cm. As the volume of the solution infused into the proximal oesophagus was increased, the sphincter pressure also rose from a median basal value of 30 (25-50) mmHg to 40 (30-50) mmHg for HCl and NaCl after 1 ml, while after 7 ml infusion, the responses were greater, 65 (45-85) mmHg for HCl, and 60 (45-80) mmHg for NaCl. In the more distal oesophagus, responses were qualitatively similar but quantitatively smaller than proximally, being 30 (25-40) mmHg for HCl and 30 (25-50) mmHg for NaCl following 1 ml and 45 (40-55) mmHg for HCl and NaCl after 7 ml. Secondary peristalsis was also induced equally by both solutions and varied with volumes infused and site of infusion in a manner similar to the sphincter responses. After a 7 ml/min acid infusion 14 (1- 40) secondary contractions/three min were recorded at 5 cm and eight (2 - 18)/three min were recorded at 20 cm. Values for saline were similar, 13 (1- 38)/three min at 5 cm and eight (4 - 25)/three min at 20 cm. Oesophageal distension by a balloon positioned 10 cm below the sphincter induced identical clearance responses to those seen after similar volumes of either acid or saline infused at the same site. These results suggest that the principal stimulus for upper oesophageal clearance is intraluminal distension and do not support the idea that the oesophagus is pH sensitive.     

Assessment of the neural defect in a dog with idiopathic megaesophagus

In a dog with megaesophagus, we studied (1) the upper (UES) and lower (LES) esophageal sphincter responses to swallowing, (2) the UES response to intraesophageal balloon distension and acid perfusion, (3) the fasting LES, stomach and upper small bowel motor activity, and (4) the LES response to intraesophageal balloon distension. The findings were compared to those in two normal dogs. In normal dogs, balloon distension (10–40 cc) and acid perfusion (0.1–0.4 N HCl) at 5, 10, and 15 cm distal to the UES produced up to 200% and 100% increases in UES pressure, respectively. Fasting LES activity in these dogs was coupled to the cyclical migrating motor complex (MMC) activity of the stomach and intestine, with phase I, random phase II, and phase III employing 40%, 40%, and 20% of cycle time, respectively. Balloon distension (10–40 cc) at 5, 10, and 15 cm proximal to the LES in phases I, II, and III produced 80–100% relaxation of the sphincter. In the dog with megaesophagus: (1) the UES and LES response to swallowing was normal; (2) balloon distension (10–40 cc) in the upper esophagus produced no significant increase (P>0.05) in UES pressure while acid perfusion (0.1–0.4 N HCl) produced a significant but relatively smaller increase (50%) in UES pressures; (3) phase I MMC activity in this dog was absent or very short in duration (<5% cycle time), the activity mostly alternating between phases II and III (75–80% and 20% cycle time, respectively); and (4) balloon distension in the distal esophagus (up to 80 cc) induced no observable relaxation (<10%) of the LES. Conclusion: The normal UES and LES response to swallowing and the presence of cyclical MMC activity in the LES indicates that the efferent neural pathways, at least to these areas, are intact in the dog with megaesophagus. Absence or decreased response of the UES and LES to intraluminal stimuli suggests that at least the afferent component of the reflex neural pathways is faulty in idiopathic megaesophagus. The location of the defect is yet to be determined.This work was supported by the Medical Research Council of Canada grant MA3353, and the Elsie Watt Foundation.     

Oesophageal motor and sensitivity abnormalities in non-obstructive dysphagia

OBJECTIVES : To evaluate oesophageal sensitivity to balloon distension in patients with non-obstructive dysphagia (NOD), and to determine its relationship with the motility pattern in response to food ingestion. PATIENTS AND METHODS : Twenty-one healthy volunteers and 19 consecutive patients complaining of NOD with normal standard manometry were included. An oesophageal sensitivity test was carried out before the manometry study with liquid and solid swallows. RESULTS : The median threshold to distension was 9 ml in control subjects and 5 ml in patients (P < 0.002). Dysphagia or odynophagia were reproduced in 15/19 (78.9%) patients during manometry with solid swallows only. The percentage of swallows with abnormal motility patterns was higher in patients than control subjects (P < 0.001). Compared with control values, sensitivity abnormality was defined by a distension threshold of < 6 ml. Motor abnormality was defined by > 19% of swallows occurring with one or more abnormal motor profiles. A total of 8/19 (42%) patients presented with the association of an abnormal sensitivity threshold and an abnormal motor pattern; 5/19 (26%) presented with isolated motor abnormalities; 4/19 (21%) patients presented with isolated abnormal sensitivity thresholds; and 2/19 (11%) patients presented without any abnormality. CONCLUSION : Manometry with solid swallows and oesophageal balloon distension are useful in characterizing NOD.     

Intestinointestinal Inhibitory Reflexes

The motor response induced by intraluminal distension of the small intestine has been well investigated. However, little is known of the myoelectrical response to intraluminal distension. The aim of this study was to investigate the effects of oral- and anal-side distension on jejunal slow waves in dogs. The study was performed in 10 healthy female hound dogs implanted with three pairs of electrodes on the jejunum and an intestinal fistula. The first study session was designed to investigate the effects of anal-side distension on jejunal myoelectrical activity in fasting state. The protocol consisted of a 30-min baseline recording, a 30-min recording during anal-side balloon distension located 5 cm distal to the most distal pair of electrodes, and another 30-min recording after distension. The second session was designed to investigate the effect of oral-side distension with the balloon 5 cm proximal to the most proximal pair of electrodes. Jejunal slow waves were severely impaired by both anal- and oral-side distension. The dominant power was significantly reduced from –2.96 ± 0.90 dB at baseline to –6.00 ± 0.64 dB during anal-side distension (P < 0.0005) and from –3.90 ± 0.85 dB at baseline to –7.17 ± 0.90 dB during oral-side distension (P < 0.001). The percentage of normal 17 to 22-cpm slow waves was significantly decreased from 97.39 ± 0.88% to 83.48 ± 3.12% during anal-side distension (P < 0.0005) and from 92.49 ± 2.42% to 68.80 ± 7.24% during oral-side distension (P < 0.002). The percentage of slow wave coupling was decreased from 95.08 ± 2.27% to 52.48 ± 7.73% during anal-side distension (P < 0.0005) and from 84.82 ± 6.75% to 49.21 ± 8.91% during oral-side distension (P < 0.001). The instability coefficient of the dominant frequency was significantly increased during anal-side distension. In conclusion, intraluminal distension of the jejunum severely impairs jejunal slow waves. The slow waves on both sides of distension become less coupled, less regular, and are of lower amplitude.     

Oesophageal and gastric motility disorders in patients categorised as having primary anorexia nervosa.

Gastrointestinal motor function in patients with primary anorexia nervosa has rarely been investigated. We studied oesophageal motor activity in 30 consecutive patients meeting standard diagnostic criteria for primary anorexia nervosa (Feighner et al; DSM III). Seven were found to suffer from achalasia instead of primary anorexia nervosa, one from diffuse oesophageal spasm and one from severe gastro-oesophageal reflux and upper oesophageal sphincter hypertonicity, while partly non-propulsive and repetitive high amplitude, long duration contractions prevailed in the lower oesophagus of another six. In four patients with oesophageal dysmotility not responding to therapy and in 12 of 15 patients with normal oesophageal manometry, gastric emptying of a semisolid meal was studied. Emptying was normal in only three but markedly delayed in 13 cases (half emptying times 97-330 min, median: 147 min, as compared with 21-119 min, median: 47 min, in 24 healthy controls). In eight patients, the effects of domperidone 10 mg iv and placebo were compared under random double blind conditions. Half emptying times were shortened significantly (p less than 0.01) by domperidone. Conclusions: symptoms of disordered upper gastrointestinal motor activity may be mistaken as indicating primary anorexia nervosa; clinical evaluation of patients with presumed primary anorexia nervosa should rule out the possibility that disordered oesophageal motor activity underlies the symptoms; delayed gastric emptying is a frequent feature in primary anorexia nervosa and might be returned to normal with domperidone.     

Diminished oesophageal traction forces with swallowing in gastro-oesophageal reflux disease and in functional dysphagia.

Relations between primary oesophageal peristaltic amplitude and traction force were studied in 30 normal volunteers, 12 patients with functional dysphagia, and 48 patients with gastro-oesophageal reflux disease, using a new intraluminal strain gauge device. Forces generated by swallowing in the normal oesophagus were 42 (35-60) g (median and interquartile range), a close positive correlation existing between traction force and contractile amplitude for each subject (r = 0.5 (0.38-0.6). Traction force increased with increasing balloon volume from 62 (50-73) g at 2 ml to 86 (70-105) g at 4 ml (p < 0.05), indicating distension related modulation of peristaltic force. Patients with oesophagitis generated lower traction forces on swallowing 30 (20-40) g compared with the normal subjects (p < 0.01), the degree of impairment being greatest in those patients with the most severe mucosal damage. Patients with gastro-oesophageal reflux without endoscopic oesophagitis also showed abnormal forces (32 22-38) g p < 0.01 v controls), which were similar to those patients with mild oesophagitis but were greater than those with severe oesophagitis (p < 0.05). In patients with functional dysphagia, forces were also impaired (28 (10-60) g p < 0.05 v controls) despite normal standard manometry. Our results show that measurement of the traction force generated by primary peristalsis provides information about oesophageal neuromuscular function that is not demonstrable by manometry alone and can be abnormal in patients with oesophageal symptoms in whom standard techniques are normal.     

Stimulation and characteristics of secondary oesophageal peristalsis in normal subjects.

The study evaluates the triggering and characteristics of secondary oesophageal peristalsis in 25 healthy volunteers. Secondary peristalsis was stimulated by rapid intraoesophageal injection of boluses of air and water, and by a five second oesophageal distension with a balloon. Air and water boluses triggered secondary peristalsis that started in the proximal oesophagus regardless of injection site. Response rates were volume dependent with 83% of the 20 ml air boluses triggering secondary peristalsis compared with 2% for the 2 ml water bolus (p < 0.0001). Response rates for air and water were similar for equal bolus volumes and were not influenced by the site of injection. In contrast, balloon distension usually induced a synchronous contraction above the balloon, with secondary peristalsis starting below the balloon after deflation. The peristaltic response rate to balloon distension was also volume dependent and the middle balloon was more effective in triggering secondary peristalsis than either the upper or lower balloons (p < 0.001). Secondary peristaltic amplitude was less than that of primary peristalsis (p < 0.001). Secondary peristaltic velocity with a water bolus was slower (p = 0.001) than that of primary peristalsis. Intravenous atropine significantly reduced secondary peristaltic responses to all stimuli. There was also a significant reduction in pressure wave amplitude for air stimulated secondary peristalsis while those for the water responses were similar. Secondary peristaltic velocity with air and water boluses was not changed by atropine. The reproducibility of testing secondary peristalsis was examined six volunteers and did not show any significant differences on separate test days in response rate and peristaltic amplitude or velocity. It is concluded that in normal subjects, secondary peristalsis can be more reliably triggered by intraoesophageal air or water infusion than balloon distension. Secondary peristaltic amplitude and velocity are stimulus but not site or volume dependent and propagation is partially mediated by cholinergic nerves.     

Secondary oesophageal peristalsis in patients with non-obstructive dysphagia.

Secondary peristalsis was investigated in 30 patients with non-obstructive dysphagia and 20 age matched controls. Oesophageal motility was recorded at 3 cm intervals along the oesophageal body. Primary peristalsis was tested with 5 ml water swallows. Secondary peristalsis was stimulated with 10 ml boluses of air and water injected in the mid-oesophagus and by distensions (5 seconds duration) with a 3 cm balloon at the same level. Primary peristalsis was normal in 19 of the 20 control subjects and in nine of the 30 patients with dysphagia; 11 patients had diffuse spasm and 10 had non-specific abnormalities of primary peristalsis. Secondary peristalsis was triggered significantly less frequently by air and water distension in dysphagia patients (median success rate of 10% for the air boluses and 0% for the water boluses) than in control subjects (50% and 30% respectively, p < 0.005), and was abnormal in six of nine patients with normal primary peristalsis, nine of 11 patients with diffuse spasm and eight of 10 patients with non-specific motor abnormalities. The median frequency of balloon induced secondary peristalsis, however, was not significantly different in the two groups (0% controls, 40% non-obstructive dysphagia, p = 0.22). For each stimulus, there were no significant differences in the response rate in the three subgroups of patients. The major pattern of failure of secondary peristalsis in response to the air and water boluses was the complete absence of any oesophageal response. The amplitude of complete secondary peristalsis triggered by the water boluses and the balloon was greater in the patients with dysphagia (p = 0.03) than in normal subjects, while the amplitude of the secondary peristaltic responses triggered by the air boluses was similar in the two groups. Secondary peristaltic velocity was also similar in normal subjects and patients with non-obstructive dysphagia. Patients with non-obstructive dysphagia show a noticeable defect in the triggering of secondary peristalsis which may make an important contribution to the delayed oesophageal bolus transit and dysphagia seen in this condition.     

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

Secondary peristalsis contributes to oesophageal acid clearance. The aim of the study was to evaluate the integrity and characteristics of secondary peristalsis in patients with gastro-oesophageal reflux disease. Studies were performed in 22 patients with reflux disease and 20 age matched controls. Oesophageal motility was recorded at 3 cm intervals along the oesophageal body. Primary peristalsis was tested with 5 ml water swallows. Secondary peristalsis was stimulated with 10 ml boluses of air and water injected in the mid-oesophagus and by 5 second distensions with a 3 cm balloon at the same level. It was found that primary peristalsis was normal in 19 of 20 control subjects and in 14 of 22 patients with reflux disease. In patients with reflux disease, intact secondary peristalsis was triggered infrequently by air and water distension (median success rate of 0% for both stimuli) and occurred significantly less frequently than in control subjects (50% and 30% respectively). The frequency of balloon induced secondary peristalsis, however, was similar in the two groups (0% controls, 20% reflux disease). The major pattern of failure of secondary peristalsis was the complete absence of any oesophageal secondary peristaltic response. The amplitudes of the intact secondary peristaltic responses were not significantly different for the two groups. Peristaltic velocity for air and balloon induced secondary peristalsis was also similar in control subjects and patients with reflux disease whereas water induced secondary peristalsis was slower in the reflux patients. In conclusion, patients with reflux disease exhibit a pronounced defect in the triggering of secondary peristalsis.     

Motor activity of the distal oesophagus and gastrooesophageal reflux.

The relationship between intraoesophageal pH value and motor activity of the lower oesophageal body and sphincter was investigated by simultaneous evaluation of intraluminal pressure and pH in 13 patients complaining of heartburn and regurgitation. One hundred and thirty one episodes of gastro-oesophageal reflux were recorded. One hundred and eighteen (90.1%) were preceded by a swallow (one to 12 seconds), 13 reflux episodes (9.9%) were not preceded by a swallow. Gastro-oesophageal refluxes preceded by swallow were accompanied by an equal number of normal and abnormal primary peristaltic sequences and, while recording at level of the lower oesophageal sphincter, occurred during inhibition of the sphincter. Frequency of abnormal primary peristalsis increased (p less than 0.01) during periods of low intraluminal pH (less than 5.0). An increase of at least 0.5 U in intraluminal pH occurred with 45.2% of normal primary peristalsis, 29.3% of abnormal primary peristalsis, 4.3% of secondary peristalsis, 3.5% of non-peristaltic contractions. The results of this study indicate that in patients with symptoms of reflux oesophagitis, gastro-oesophageal reflux appears to be related to swallow-induced lower oesophageal sphincter inhibition and not related to abnormal motor activity of the distal oesophageal body where an increased frequency of abnormal primary peristalsis appears to occur during low intraluminal pH and primary peristalsis appears to be the most important mechanism of oesophageal clearing.     

Fundic balloon distension stimulates antral and duodenal motility in man

Distension of the intestine triggers the peristaltic reflex, which consists of orad contraction and aborad relaxation. Whether a similar response occurs in the human stomach is unclear. Our aim was to investigate the antral and duodenal motor response(s) to mechanical distension of the proximal stomach. In six healthy volunteers, a large compliant balloon was placed in the proximal stomach. Alongside this a water-perfused manometry probe with six sensors was placed to measure the antral and duodenal motility. Pressure activity was assessed before and during balloon distension. In five of six subjects, balloon distension triggered a salvo of antral pressure waves within 3–5 min, some of which propagated into the duodenum. The amplitude of waves was higher (P < 0.05) at the antrum than at the duodenum. The area under the curve of pressure waves was higher (P < 0.05) at the antrum than at the duodenum. In conclusion, distension of the proximal stomach, at or below the threshold for perception, evokes phasic motor activity in the antrum and duodenum. Thus, the gastric response to distension differs from that observed during the intestinal peristaltic reflex.     

Oesophageal intraluminal impedance can identify subtle bolus transit abnormalities in patients with mild oesophagitis

In a subgroup of patients with non-erosive gastroesophageal reflux disease (GORD) or mild oesophagitis, acid clearance is prolonged in spite of favourable gravity and normal or minimally impaired oesophageal peristalsis. Dysphagia is rare in this group but might also be present or develop after anti-reflux surgery. The causal relationship between prolonged clearance or dysphagia and oesophageal body dysmotility in these patients is not completely clear. New techniques are now available to assess oesophageal motility and transit and might help to detect more subtle defects underlying functional impairment in patients with GORD. Combined video-fluoroscopy and intraluminal impedance indicate an excellent correlation between both methods in detecting oesophageal bolus transit. Combined intraluminal impedance and manometry has the capability to evaluate oesophageal contractions and bolus transit without the use of radiation. Subtle bolus transit abnormalities were identified in a small proportion of patients with mild oesophagits and normal oesophageal peristalsis. Outcome data are needed to evaluate the prognostic value of combined manometry-impedance in patients with GORD undergoing anti-reflux surgery.     

Rectal sensorimotor dysfunction in patients with urge faecal incontinence: evidence from prolonged manometric studies

BACKGROUND AND AIMS: Although external anal sphincter dysfunction is the major cause of urge faecal incontinence, approximately 50% of such patients have evidence of rectal hypersensitivity and report exaggerated stool frequency and urgency. The contribution of rectosigmoid contractile activity to the pathophysiology of this condition is unclear, and thus the relations between symptoms, rectal sensation, and rectosigmoid motor function were investigated. METHODS: Fifty two consecutive patients with urge faecal incontinence, referred to a tertiary surgical centre, and 24 volunteers, underwent comprehensive anorectal physiological investigation, including prolonged rectosigmoid manometry. Patients were classified on the basis of balloon distension thresholds into those with rectal hypersensitivity (n = 27) and those with normal rectal sensation (n = 25). Automated quantitative analysis of overall rectosigmoid contractile activities and, specifically, high amplitude contractions and rectal motor complex activity was performed. RESULTS: External anal sphincter dysfunction was similar in both patient groups. Overall, phasic activity and high amplitude contraction frequency were greater, and rectal motor complex variables significantly altered, in those with rectal hypersensitivity. Symptoms, more prevalent in the rectal hypersensitivity group, were also more often associated with rectosigmoid contractile events. For individuals, reduced compliance and increased rectal motor complex frequency were only observed in patients with rectal hypersensitivity. CONCLUSIONS: We have identified a subset of patients with urge faecal incontinence-namely, those with rectal hypersensitivity-who demonstrated increased symptoms, enhanced perception, reduced compliance, and exaggerated rectosigmoid motor activity. Comprehensive assessment of rectosigmoid sensorimotor function, in addition to evaluation of anal function, should be considered in the investigation of patients with urge faecal incontinence.     

Relation between rectal sensation and anal function in normal subjects and patients with faecal incontinence.

The relation between sensory perception of rapid balloon distension of the rectum and the motor responses of the rectum and external and internal anal sphincters in 27 normal subjects and 16 patients with faecal incontinence who had impaired rectal sensation but normal sphincter pressures was studied. In both patients and normal subjects, the onset and duration of rectal sensation correlated closely with the external anal sphincter electrical activity (r = 0.8, p less than 0.0001) and with rectal contraction (r = 0.51, p less than 0.001), but not with internal sphincter relaxation. All normal subjects perceived a rectal sensation within one second of rapid inflation of a rectal balloon with volumes of 20 ml or less air. Six patients did not perceive any rectal sensation until 60 ml had been introduced, while in the remaining nine patients the sensation was delayed by at least two seconds. Internal sphincter relaxation occurred before the sensation was perceived in three of 27 normal subjects and 11 of 16 patients (p less than 0.001), and could be associated with anal leakage, which stopped as soon as sensation was perceived. The lowest rectal volumes required to induce anal relaxation, to cause sustained relaxation, or to elicit sensations of a desire to defecate or pain were similar in patients and normal subjects. In conclusion, these results show the close association between rectal sensation and external anal sphincter contraction, and show that faecal incontinence may occur as a result of delayed or absent external anal sphincter contraction when the internal anal sphincter is relaxed.     

Sigmoid motility stimulated by luminal distention. Changes in the motility response in constipation by the slowing down of left colonic transit

The aim of our study was to develop a new technique of sigmoid manometry using standardized luminal distensions and to compare patterns of colonic motility following distension in normal subjects and in constipated patients. Eight subjects without colonic disturbances and 8 constipated patients with delayed transit time of the left colon as shown by radiopaque markers were investigated. Sigmoid motor activity was recorded by measuring pressure in a distending latex balloon placed at 25 cm from the anus. Inflations were maintained during 250 s and separated by 60 s recovery periods of deflation. Volumes of air (V) were increased until the patient reported abdominal pain (VMT). For each distension level, the resistance to distension of the bowel wall evaluated by the baseline adaptative pressure (P) and the contractile activity (A) quantified by planimetry of the active contractile activity (A) quantified by planimetry of the active contraction waves superimposed to P were assessed. In normal subjects, VMT was 147 +/- 9 ml. P increased linearly with V (p less than 0.03) up to 4,336 +/- 876 Pa. A increased with V until VMT/2 reached the maximum of 389 +/- 72 Pa*; for higher volumes A decreased significantly with to 166 +/- 46 Pa for VMT. Reference to controls, the constipated patients had a decreased VMT (61 +/- 4 ml). P increase at VMT (5,084 +/- 753 Pa) and A maximal value (387 +/- 176 Pa) were not different.(ABSTRACT TRUNCATED AT 250 WORDS)     

Oesophageal propulsive force and its relation to manometric pressure.

A fixed volume capsule incorporating a force transducer and a side hole for manometric measurements was constructed and calibrated. Simultaneous measurements of the propulsive (aboral) force and the manometric pressure (intraluminal pressure) were made at 5, 10, and 15 cm above the lower oesophageal sphincter and in response to dry and wet (5, 10, and 15 ml) swallows. The propulsive force and manometric pressure waves had a simultaneous onset and were of similar duration. Peak values of propulsive force for wet swallows increased significantly as measurements were made progressively more distally within the oesophagus and were greatest in the distal oesophagus. The association between manometric pressure and propulsive force is not strong (r = 0.61) suggesting that intraluminal pressure is a poor predictor of propulsive force and hence an unreliable measure of oesophageal 'function'.     

Inhibition by female sex steroids of peristalsis in the guinea pig small intestine

AIMS: The effects of steroid hormones on propulsive peristalsis in the intestine were investigated in order to compare their adverse effect profile on this clinically most important motor pattern. METHODS: Peristalsis in isolated segments of the guinea pig small intestine was triggered by luminal distension and recorded via the peristalsis-associated changes of the intraluminal pressure. Drug effects on muscular activity were investigated in a circular muscle preparation of the ileum. RESULTS: Estradiol and progesterone, but not testosterone, hydrocortisone or cholesterol (each at 3-30 microM), caused a prompt and concentration-related increase in the peristaltic pressure threshold at which propulsive muscle contractions were elicited. Mifepristone (RU-486; 30 microM) did not prevent the inhibitory effect of progesterone, but blocked peristalsis per se. Pharmacological blockade of inhibitory neural pathways with N(G)-nitro-L-arginine methyl ester (nitric oxide synthase inhibitor), naloxone (opioid receptor antagonist), apamin or suramin plus pyridoxal phosphate-6-azophenyl-2',4'-disulphonic acid (P2 purinoceptor blockers) counteracted the inhibitory effect of submaximally (10 microM), but not maximally (30 microM), effective concentrations of progesterone. Estradiol and progesterone depressed circular muscle contractions evoked by cholecystokinin octapeptide to a larger degree than responses to the tachykinin NK(1) receptor agonist GR-73,632. CONCLUSION: The peristaltic motor inhibition caused by sex steroids at micromolar concentrations arises primarily from a depressant action on intestinal muscle activity and may be particularly relevant for high-dose regimens of mifepristone.