Site Of Distension Research Articles

Impaired contractility and remodeling of the upper gastrointestinal tract in diabetes mellitus type-1

To investigate that both the neuronal function of the contractile system and structural apparatus of the gastrointestinal tract are affected in patients with longstanding diabetes and auto mic neuropathy. The evoked esophageal and duodenal contractile activity to standardized bag distension was assessed using a specialized ultrasound-based probe. Twelve type-1 diabetic patients with autonomic neuropathy and severe gastrointestinal symptoms and 12 healthy controls were studied. The geometry and biomechanical parameters (strain, tension/stress, and stiffness) were assessed. The diabetic patients had increased frequency of distension-induced contractions (6.0 +/- 0.6 vs 3.3 +/- 0.5, P < 0.001). This increased reactivity was correlated with the duration of the disease (P = 0.009). Impaired coordination of the contractile activity in diabetic patients was demonstrated as imbalance between the time required to evoke the first contraction at the distension site and proximal to it (1.5 +/- 0.6 vs 0.5 +/- 0.1, P = 0.03). The esophageal wall and especially the mucosa-submucosa layer had increased thickness in the patients (P < 0.001), and the longitudinal and radial compressive stretch was less in diabetics (P < 0.001). The esophageal and duodenal wall stiffness and circumferential deformation induced by the distensions were not affected in the patients (all P > 0.14). The impaired contractile activity with an imbalance in the distension-induced contractions likely reflects neuronal abnormalities due to autonomic neuropathy. However, structural changes and remodeling of the gastrointestinal tract are also evident and may add to the neuronal changes. This may contribute to the pathophysiology of diabetic gut dysfunction and impact on future management of diabetic patients with gastrointestinal symptoms.

Biomechanical properties of the anterior urethra of the male rabbit--a study using impedance planimetry.

To evaluate the anterior urethra of the male rabbit regarding its luminal cross-sectional area (CSA), CSA distensibility, circumferential tension-strain relation, histology and the collagen content of the tissue. material and methods: Nineteen rabbits were examined with impedance planimetry by distending the urethra at the passage from the spongious to the bulbous part and 1 cm proximally in the bulbous part. Four weeks later, eight rabbits underwent a second examination. After the measurements the urethras were processed for either histology or determination of collagen content. The urethras from six additional rabbits served as controls for histology and collagen content. The CSA and the CSA distensibility were smaller at the distal than the proximal distension site. At both sites the CSA distensibility was high at low luminal pressure loads and decreased with increasing pressure. The circumferential tension-strain plot displayed an exponential relation, with a steeper slope distally than proximally. Repeated biomechanical investigation revealed a significantly increased CSA and a decreased slope of the circumferential tension-strain relation at both distension sites. The biomechanical investigation induced abrasion of the epithelium, extravasation of erythrocytes and separation of the collagen fibres, suggesting oedema of the luminal part of the wall. After 4 weeks the epithelium had changed from transitional to stratified, squamous and often keratinized epithelium and the collagen beneath the epithelium formed a dense network instead of wavy lines as seen in the control urethras. The collagen content was larger at the distal than the proximal distension site. No change in collagen content could be demonstrated between the urethras investigated once or twice with impedance planimetry. The non-linear pressure-CSA, pressure-CSA distensibility and circumferential tension-strain relations found at both distension sites demonstrate that the urethra yields readily at low pressures, thus facilitating flow. At higher pressure loads, the tissue becomes less distensible, a property that protects it against over-distension and damage. Impedance planimetry cannot be used to study before-and-after phenomena as the biomechanical investigation changed both the histology and the biomechanical properties of the rabbit urethra.

Small intestinal transit does not adequately represent postoperative paralytic ileus in rats.

Small intestinal transit (SIT) has often been regarded as an index of pathophysiological state of postoperative ileus (PI) in rats. The reliability of SIT as an index of PI was examined in the present study. PI was induced via abdominal surgery (i.e., laparotomy with evisceration and manipulation) in rats. For one group of PI-induced rats, SIT of a charcoal test meal was measured. When necessary, the physical state (i.e., severity and site of distension) of the gastrointestinal (GI) tract in each rat was visually examined. For another group of PI-induced rats, abdominal X-ray radiographs were obtained after introducing the barium sulfate suspension. The abdomen was then opened and the physical state of the GI tract was visually examined. The SIT was decreased in most of the PI-induced rats, and the GI distension was observed, with substantial intersubject variations, in all of the PI-induced rats. However, no linear relationship was evident between the SIT and the severity of GI distension (e.g., at 20 h after PI induction). Instead, the severity and site of GI distension could be monitored by the X-ray radiology. Therefore, the use of SIT as an index of Pi should be substantially limited.

Oesophageal pressure-cross-sectional area distributions and secondary peristalsis in relation to subclassification of systemic sclerosis.

The aim of the present study was to correlate the severity of oesophageal motor dysfunction with the severity of cutaneous disease in systemic sclerosis (SS). Patients were divided into three groups based on the degree of skin involvement: type I, acrosclerosis distal to the wrist; type II, scleroderma extending above the wrist in proximal direction; type III, diffuse cutaneous systemic sclerosis. Impedance planimetry employing distensions with pressures up to 5 kPa with the concomitant measurement of oesophageal cross-sectional area (CSA) was used in combination with standard oesophageal manometry. Measurements were made at 7 and 15 cm above the lower oesophageal sphincter (LOS). Thirty patients (16 type I, six type II and eight type III patients) and 23 normal controls were included. LOS pressure was lower in SS patients than in normal patients, with the lowest values in type III. The CSAs were higher in SS patients than in controls at both sites (P < 0.001). The CSAs at the distal site were highest in type III, as compared to type I and II (P < 0.03). The CSA at the highest induced pressure (5.0 kPa) was 613 +/- 45, 719 +/- 79, and 808 +/- 115 mm2 in types I, II and III, respectively. No differences in CSA were found at the proximal site between the three types of SS. The distensibility did not differ between SS and normal patients at the distal site. The distensibility was lowest in SS patients (P < 0.001) at the proximal distension site. The distensibility did not vary with the type of SS at either site. Significant differences in contraction frequency of the secondary peristalsis as function of wall tension were demonstrated between the SS patients and controls at the distal site (P < 0.05). No differences were found at the proximal site. The contraction frequency and amplitude at the distal and proximal sites did not differ among the three types. In conclusion for most parameters studied, SS patients differed from normal patients. Among SS types, the most pronounced changes were found in type III.

Initiation of distension-induced descending peristaltic reflex in opossum esophagus: role of muscle contractility.

The balloon distension (BD)-induced descending peristaltic reflex in the opossum smooth muscle esophagus is abolished in vitro when a Ca(2+)-free Krebs solution is placed at the site of distension, suggesting that either synaptic transmission occurs at the origin of the reflex or initiation of the reflex requires the development of muscle tension in response to BD. To test the latter possibility, an 8- to 10-cm length of smooth muscle esophagus was placed in a dual-chamber organ bath, isolating the stimulating (orad) from the recording site (aborad). Nifedipine addition to the orad chamber (i.e., site of distension) inhibited the BD-induced "off" contractions in both chambers in a concentration-dependent manner. However, the aborad response to electrical field stimulation (EFS) was unaffected. Atropine addition to the orad chamber had no effect on BD or EFS responses in either chamber. To examine the effects of these agents on tonic contractility, an isobaric barostat was employed. Pressure-volume curves were not altered by Ca(2+)-free Krebs solution, nifedipine, or TTX, suggesting that resting esophageal tone is not dependent on neural factors or muscle contractility. However, both Ca(2+)-free Krebs solution and nifedipine markedly decreased phasic contractions over the top of the distending bag. These observations suggest that local, stretch-induced phasic muscle contraction is required for initiation of the BD-induced descending peristaltic reflex.

Distension-related responses in circular and longitudinal muscle of the human esophagus: an ultrasonographic study.

Both circular muscles (CM) and longitudinal muscles (LM) of the esophagus participate in peristalsis. Various measurement techniques have yielded conflicting information as to the temporal correlation between contraction in the two muscle layers. High-frequency intraluminal ultrasound (HFIUS) is a novel technique to detect contraction of LM and CM of the esophagus. We investigated the temporal correlation between the CM and LM contraction during ascending excitatory and descending inhibitory reflexes using HFIUS. A manometric catheter equipped with two balloons and a 12.5-MHz ultrasound transducer catheter was used to study 10 normal healthy subjects. The changes in muscle thickness and pressure, proximal and distal to esophageal distension, were recorded at 5 and 10 cm above the lower esophageal sphincter (LES). The esophageal distension induced an increase in pressure and an increase in muscle thickness of both CM and LM layers proximal to the distension site. The onset of increase in muscle thickness and peak muscle thickness in two layers occurred at the same time. There was a close temporal correlation between the changes in pressure and changes in muscle thickness. Atropine inhibited the distension-related pressure and muscle thickness increase in both layers. Distal to the esophageal distension, there was no change in pressure but a decrease in the thickness of the two muscle layers. The decrease in muscle thickness of the two layers occurred at the same time. The responses of the two muscle layers to distension were similar at 5- and 10-cm sites above the LES. HFIUS is a relatively noninvasive technique to study the LM layer response during peristalsis in vivo. Our data indicate that the two muscle layers may contract and relax together during distension-related peristaltic reflexes in the esophagus.

Impedance planimetric characterization of esophagus in systemic sclerosis patients with severe involvement of esophagus.

This study was designed to evaluate the distensibility and secondary peristalsis of the esophagus in patients suffering from systemic sclerosis with severe esophageal involvement. Balloon distension with impedance planimetric measurement of luminal cross-sectional area was done 7 and 15 cm above the lower esophageal sphincter in 13 patients and nine healthy controls. The controls were studied both with and without receiving the anticholinergic drug butylscopolamine. The cross-sectional area--pressure relations were nonlinear with the largest cross-sectional area in patients at both measuring sites when compared to controls (P < 0.001). The anticholinergic drug butylscopolamine increased the cross-sectional area in controls (P < 0.001). The cross-sectional area distensibility, defined as CSA0(-1) delta CSA delta P-1 did not differ between patients and controls. Balloon distensions elicited contractions proximal to the distension site. The amplitude and frequency of contractions at the distal distension site were significantly reduced in the patients when compared to the controls (P < 0.05). In conclusion, the distal esophagus is most severely affected in patients with systemic sclerosis with increased cross-sectional area and impaired peristalsis.

Quantification of the oesophageal peristaltic reflex in man.

The peristaltic reflex represents the basis of peristalsis and has two components, ascending contraction above and descending relaxation below the site of distension. Studies of the two components of the reflex in the human oesophagus performed by concurrent monitoring of oesophageal body and lower oesophageal sphincter (LOS) motility are lacking. We investigated the peristaltic reflex in eight healthy volunteers (aged 19-25 years; five male, three female) by two series of eight graded (3-10 mL) balloon distensions performed 11 cm above the LOS, monitoring motor activity in the oesophageal body both above and below the balloon and in the LOS (sleeve sensor). During balloon distension both ascending contraction, as assessed by contractile activity above the balloon, and descending relaxation, as assessed by LOS relaxation, increased linearly with increasing inflation volumes (r = 0.6 and r = 0.8, respectively, both P < 0.0001). The threshold for descending relaxation was lower than that for ascending contraction. The contractile response of the body below the balloon was always lower than above the balloon and occurred with a higher (P < 0.05) frequency at 6 and 7 mL compared to 3, 4 and 10 mL. After balloon deflation an oesophageal contraction, usually accompanied by an LOS contraction, occurred with increasing frequency as the balloon volume increased. Our experimental model allows detailed assessment of the two components of the peristaltic reflex in the human oesophagus in vivo and should prove useful in future studies on the physiology and pathophysiology of this reflex.

Frequency of gastric pacesetter potential depends on volume and site of distension

Little is known about the response of the frequency of gastric pacesetter potential (PP) to luminal distension. When volume distension occurs as a result of a meal, gastric emptying may play an important role, since the site of distension shifts as the meal is displaced from the stomach to the small bowel. In this study, using does equipped with duodenal fistulas and serosal electrodes on the antrum, we compared the frequency of gastric PP during the course of gastric emptying while isolating the volume distension to either the stomach or the small bowel. We found that 1) the frequency of gastric PP decreased linearly with greater initial meal volume when volume distension was isolated to either the stomach -P<0.05, analysis of variance (ANOVA)- or small bowel (P<0.01, ANOVA), and 2) the frequency of gastric PP decreased linearly with increased volume remaining in the stomach or increased volume entering the small intestine. We conclude that the frequency of gastric PP depends on the volume and site of distension.

Biomechanical characteristics of the human esophagus.

Biomechanical wall properties of the human esophagus were studied. A probe, with a balloon designed for simultaneous measurement of cross-sectional area and intraluminal pressure, was placed in the esophagus 30 cm from the incisors. Tone was not detected before inflation of the balloon. When the balloon was inflated stepwise with pressures up to 40 cm H2O (30.7 mmHg), measurement of cross-sectional area allowed calculation of distensibility and circumferential wall tension. Balloon cross-sectional area increased linearly with increased balloon pressure. Balloon distension induced contractions, both proximal to the balloon and at the site of distension, at a balloon pressure of about 15 cm H2O (11.5 mm Hg). The cross-sectional area for the threshold for distension induced contractions was 153 +/- 12 mm2 (diameter 14 mm). At the onset of these contractions, the contraction force was 15-20 cm H2O (11.5-15.3 mm Hg) and it increased to 47-58 cm H2O (36.1-44 mm Hg) at a balloon pressure of 20-40 cm H2O (15.3-30.7 mm Hg). Circumferential wall tension increased with increasing intraluminal pressure in an almost exponential manner. The pressure elastic modulus increased steeply at lower balloon pressures (10-20 cm H2O) (7.7-11.5 mm Hg), but at higher balloon pressures (20-40 cm H2O) (15.3-30.7 mm Hg) this increase was less. The circumferential wall tension and wall stiffness of the human esophagus increased with increasing balloon pressure and cross-sectional area. When a threshold is reached, distension induced contractions both proximal and distal to the balloon and at the distension site.

The influence of neuronal 5-hydroxytryptamine receptor antagonists on non-cholinergic ganglionic transmission in the guinea-pig enteric excitatory reflex.

A partitioned bath made it possible to separate the site of recording of the ascending excitatory reflex of the ileal circular muscle (oral compartment) from the site of reflex induction (caudal compartment), evoked by inflating an intraluminal balloon. In the caudal compartment, blockade of cholinergic ganglionic transmission by hexamethonium (100 microM) and hyoscine (0.3 microM) caused an approximately 65% reduction in the amplitude of reflex contractions, suggesting that the remaining response was mediated by non-cholinergic transmission near the distension site. This non-cholinergic component of ganglionic transmission was insensitive to the action of methiothepin (1 microM), ondansetron (1 microM), tropisetron (1.5 microM), DAU 6285 (1 microM) and renzapride (1 microM), agents that antagonize the action of 5-hydroxytryptamine (5-HT) at neural 5-HT1-like, 5-HT3, 5-HT4 and putative 5-HT1P receptors. These findings suggest that the neural pathways subserving non-cholinergic ganglionic transmission in the ascending excitatory reflex in the guinea-pig ileum do not involve 5-HT as neurotransmitter.

Biomechanical wall properties in the isolated perfused porcine duodenum: an experimental study using impedance planimetry

AbstractThe aims were to investigate duodenal biomechanical wall properties and properties of the ascending peristaltic reflex using impedance planimetry in the isolated perfused porcine duodenum. Stepwise inflation from 0.5 to 3.0 kPa of an intraluminal duodenal balloon, in which the pressure and balloon cross‐sectional area (Bcsa) were measured simultaneously, provided the distension stimulus. The biomechanical wall parameters were calculated from these measurements.In‐vitro test of the measurement system demonstrated that it was sufficient for biomechanical studies. Balloon inflation induced a phase of rapid distension followed approximately after 2–6 s by a phase of slow Bcsa increase. In non‐relaxed segments, contractile activity was recorded both proximal to and at the site of distension. This activity started immediately after inflation and it usually disappeared within 20 s. Bcsa always reached equilibrium within the 2‐min inflation period. The circumferential wall tension and the pressure elastic modulus increased from 4.4 (3.9–4.7) kPa mm and 3.0 (2.4–3.6) kPa at low balloon pressures to 36.5 (33.3–39.3) kPa mm and 26.1 (20.7–32.8) kPa at a balloon pressure of 3 kPa. During muscle relaxation, the duodenum showed a viscoelastic behaviour with an immediate quick phase of Bcsa increase followed by a slow viscous phase. The latter fitted best with the mono‐exponential function f(x) =αx (1–eβt).The model provides the opportunity for studying duodenal biomechanical wall properties in an intact organ model. The behaviour of the present duodenal model is compatible with a Maxwell model.

Effect of intraesophageal location and muscarinic blockade on balloon distension-induced chest pain

Intraesophageal balloon distension has been introduced recently as a provocative test in the assessment of patients with noncardiac chest pain. In order to examine the effect of balloon location and muscarinic blockade on distension-induced pain, 10 asymptomatic male volunteers were studied on two separate days using a low-compliance perfused manometry system that incorporated a silicone rubber balloon. Five-second-duration balloon distensions using balloon volumes of 2.5, 5, 7.5, and 10 ml of air were performed with the balloon located both 16 cm (proximal site) and 6 cm (distal site) above the lower esophageal sphincter (LES) before and after administration of atropine (10 micrograms/kg intravenously) or placebo in a randomized double-blind fashion. A standardized scoring system was used to assess the balloon distension-induced pain. Pain scores varied directly with balloon volume but were consistently higher with the balloon located at the proximal site versus the distal site. This was not associated with any differences in intraballoon pressures between the two sites; however, contraction amplitude orad to the balloon was greater with balloon distension at the proximal site. Atropine significantly decreased pain sensation scores with the balloon located distally but not proximally. This attenuation was not associated with significant changes in intraballoon pressures; however, contractions orad to the balloon were markedly inhibited by atropine with distal but not with proximal distension. These studies indicate that balloon distension-induced pain varies depending on the location of distension. This difference is not explained by differences in esophageal wall tension at the site of distension.(ABSTRACT TRUNCATED AT 250 WORDS)

Distension-evoked ascending and descending reflexes in the circular muscle of guinea-pig ileum: an intracellular study

Reflex responses evoked by distension of the guinea-pig small intestine were recorded from the circular muscle with intracellular microelectrodes. For this purpose a mechanically stable preparation that allowed the intestinal wall to be distended within 9 mm of the recording site was developed. A segment of intestine was opened along the mesenteric border and pinned mucosa uppermost over a balloon set in the base of an organ bath, so that inflation of the balloon could distend the intestinal wall without simultaneously pushing against the mucosa. Compound excitatory junction potentials (EJPs) and compound inhibitory junction potentials (IJPs) were recorded at sites up to 40 mm oral and anal to the distending stimulus, respectively. The compound EJPs recorded orally had amplitudes of up to 24 mV and declined to baseline during distensions that exceeded 10–15 s. Distensions at intervals of less than 20 s evoked successively smaller oral compound EJPs; after four distensions in 30 s the amplitude of the compound EJP had fallen to less than 10%. The amplitude of the oral compound EJP was reduced by hyoscine (1 μM), but the extent of the reduction depended on the degree of distension; responses to mild stimuli were blocked, whereas those to strong stimuli were only slightly reduced. The amplitude of the hyoscine-resistant component of the compound EJP was markedly reduced by antagonists of substance P receptors in the muscle. In the presence of muscarinic and substance P receptor antagonists, a transient compound IJP could be detected on the oral side of the stimulus. The compound IJPs recorded anal to the distension had amplitudes up to 22 mV but the potential returned to baseline during prolonged distension. In the presence of hyoscine (1 μM) some inhibitory activity continued throughout prolonged stimuli. Compound IJP amplitudes were not significantly reduced by repeated distensions separated by more than 6 s. At anal sites a transient depolarization (off-response) was recorded immediately following the termination of a distension in some preparations. The off-response was unaffected by hyoscine and was more readily observed after the further addition of substance P antagonists. The compound IJPs were almost completely blocked by apamin (0.2 μM). The compound EJPs and IJPs recorded orally were blocked by hexamethonium (100 μM), but the amplitudes of compound IJPs recorded anally were significantly reduced by hexamethonium (100–200 μM) only at recording sites greater than 15 mm from the centre of the balloon. The off-response was reduced by hexamethonium at all sites. All responses to distension were blocked by tetrodotoxin (0.5 μM). Oral compound EJPs and anal compound IJPs of normal amplitude could still be evoked after removal of the mucosa and nearly all circular muscle from the site of distension. Such lesions did not prevent transmission of these reflexes along the intestine. Thus, both sensory neurons and the nervous pathways activated by stretch lie within the myenteric plexus.

A pharmacological analysis of the neuronal circuitry involved in distension-evoked enteric excitatory reflex

Isolated segments of guinea-pig small intestine were set up in a partitioned bath to study the enteric excitatory reflex evoked by distension. The gut was distended by a rubber balloon inserted at the aboral end and contractions of the circular muscle were recorded at the oral end. The oral and aboral ends of the gut were separated by an intermediate compartment of the bath. Inflation of the intraluminal balloon with 0.075–0.35 ml water elicited reproducible and distension-dependent contraction. This enteric orally directed (ascending) excitatory reflex was abolished by tetrodotoxin irrespective of the compartment in which it was applied. Hyoscine (0.3 μM) almost abolished the enteric excitatory reflex when it was applied to the oral compartment. This indicates that the transmission from the final motor neurons to the circular muscle is mainly cholinergic, acting via muscarinic receptors. Hyoscine had no effect on the enteric excitatory reflex when added to the intermediate compartment. When hyoscine was added to the aboral compartment, it decreased the enteric excitatory reflex elicited by low distension stimuli to 70% of control and decreased the enteric excitatory reflex elicited by higher distension stimuli to 95% of control. This indicates that ganglionic transmission involving muscarinic receptors at the site of distension in the aboral bath contributes to the enteric excitatory reflex. Hexamethonium (100 μM) greatly depressed the enteric excitatory reflex when applied to any compartment indicating that nicotinic transmission is most important in the afferent, intermediate and efferent components of the reflex and that the reflex pathway involves a polysynaptic chain of cholinergic interneurons. With both cholinergic receptor antagonists in the aboral compartment, the enteric excitatory reflex elicited by 0.3 ml distension was still 38% of the control response indicating that a significant component of the reflex in the vicinity of the initiation of the reflex is mediated by non-cholinergic ganglionic transmission. It is proposed that the enteric excitatory reflex involves mechanosensory neurons, which, depending on the intensity of the stimuli, release acetylcholine and a non-cholinergic transmitter to provide fast nicotinic, slow muscarinic, and slow non-cholinergic inputs to cholinergic interneurons. These form a polysynaptic, orally directed, pathway which utilize fast nicotinic transmission and activates the final cholinergic motor neurons which contract the circular muscle via muscarinic receptors.

Evaluation of a new and potent cholecystokinin antagonist on motor responses of the guinea-pig intestine.

The potency and selectivity of D,L-4-(3,4-dichloro-benzoyl-amino)-5-(dipentyl-amino)-5-oxo-pen tan oic acid (CR 1409) as a cholecystokinin (CCK) antagonist was investigated on motor responses of the longitudinal and circular muscles of the guinea-pig isolated ileum. CR 1409 was further used to examine whether nerve-mediated motor responses to electrical field stimulation or distension of the gut wall may involve the release of CCK-like peptides. CR 1409 (0.06-2.1 microM) antagonized longitudinal muscle responses to ceruletide (caerulein, a CCK-related decapeptide) in a concentration dependent and competitive manner (pA2 7.77); responses to CCK-octapeptide (CCK-8) were antagonized with a similar potency. Contractions of the circular muscle evoked by ceruletide were also blocked by CR 1409 (0.2-0.4 microM). Longitudinal muscle contractions in response to dimethylphenylpiperazinium, bethanechol, histamine, substance P, or 5-hydroxytryptamine (5-HT), and circular muscle contractions evoked by acetylcholine, 5-HT, substance P, or substance K were not altered by CR 1409 (0.4 microM). Longitudinal muscle contractions induced by electrical field stimulation (with pulses delivered at 0.05 and 1 Hz in the absence, and at 5 Hz in the presence of atropine) were not or only slightly reduced by CR 1409 (0.4 microM). Longitudinal contractions due to activation of extrinsic nerves by capsaicin remained unaltered in the presence of CR 1409 (0.4 microM). Reflex contractions of the circular muscle, induced by balloon distension and recorded orally to the site of distension, and peristaltic activity elicited by intraluminal infusion of Tyrode solution remained unaffected by CR 1409 (0.4 microM). 5 These findings indicate that CR 1409 is a potent and selective antagonist of CCK-like peptides in the guinea-pig ileum. The results do not provide any evidence that CCK-like peptides, released from extrinsic or intrinsic neurones, are involved in nerve-mediated contractions of intestinal muscle and in the peristaltic reflex.

Effect of pancreatic polypeptide on the motility of the guinea-pig small intestine in vitro

The effect of porcine pancreatic polypeptide (PP) on the motor activity of the longitudinal and circular muscles of the guinea-pig isolated small intestine was investigated. PP (0.2–20 nM) inhibited cholinergic contractions of the longitudinal muscle in response to electrical field stimulation, the maximal effect being a 30% reduction of the contraction amplitude. Carbachol-induced contractions of the longitudinal muscle were not affected by PP (10 nM). PP (0.3–30 nM) also inhibited reflex contractions of the circular muscle elicited by balloon distension and recorded orally to the site of distension; the maximal effect was a 80% reduction of the reflex contraction. In contrast, carbachol-induced contractions of the circular muscle remained unaltered by PP (10 nM). It was further found that PP (10 and 100 nM) enhanced the threshold intraluminal pressure at which peristaltic waves were triggered. All these effects of PP appeared to be transient. Taken together, these data indicate that PP does not act on intestinal smooth muscle but can modulate the activity of certain enteric neurones which are involved in the regulation of intestinal motility.

Intrinsic reflexes underlying peristalsis in the small intestine of the domestic fowl.

Peristalsis in the chicken small intestine was studied using either a modified Trendelenburg method or a technique in which changes in circular muscle activity were recorded in response to application of a localized radial distension. A localized radial distension had no effect on either the resting tension or the spontaneous activity of the circular muscle on the oral side of distension. On the aboral side of the distension a transient contraction was recorded in the ileum and jejunum after a mean delay of 2.74 s at 37 degrees C. In about a third of the preparations a tonic contraction was also present which persisted for as long as distension was maintained. The transient contraction was blocked by hyoscine (0.6-2.3 microM) and hexamethonium (275 microM); whereas the tonic contraction persisted in the presence of hyoscine. Both types of contraction were blocked by tetrodotoxin (0.31 microM). No such responses were recorded in the duodenum. The descending excitatory reflex responses were followed in all preparations by a fall in the amplitude and frequency of spontaneous contractions and in a few preparations by a concomitant fall in the tone of the circular muscle lasting for up to 3 min. This inhibitory component of the descending reflex was not blocked by guanethidine (3-10 microM). The transient contraction, which originated most frequently at the site of distension, always propagated aborally at a mean speed of 14.2 mm s-1. Surgical interruption of the longitudinal muscle and myenteric plexus effectively blocked the transmission of the excitatory and inhibitory components of the descending reflex past the site of the lesion. In the modified Trendelenburg apparatus raising the intraluminal pressure elicited peristalsis in the isolated ileum. Peristaltic contractions never started at the most oral end of the preparation but appeared instead at any other point on the ileum. This resulted in several contractions contributing to each emptying cycle. Peristalsis was blocked by tetrodotoxin (0.31 microM). These results are discussed in the terms of the organization of the descending reflex. It is suggested that within the enteric nervous system of the ileum and jejunum of the chicken, there are cholinergic and non-cholinergic excitatory neurones and non-adrenergic inhibitory neurones. The results of this study demonstrate that neurogenic peristalsis in the avian small intestine does not conform to the 'law of the intestine' as originally postulated by Bayliss & Starling (1899).

Peristalsis and antiperistalsis in the chicken caecum are myogenic.

Peristalsis in the chicken caecum was investigated by recording the responses of isolated segments of the caecum to either fluid distension using a modified Trendelenburg apparatus or by monitoring circular muscle activity following localized radial distension of adjacent areas. Raising the intraluminal pressure did not initiate peristalsis except in the presence of tetrodotoxin, local anaesthetics and high concentrations of phentolamine. The effect of these drugs was reversible. Localized distension generally produced either a small relaxation of the circular muscle or no response at all on both sides of the site of distension. After exposure to tetrodotoxin one, or more (usually several), rhythmic propogating contractions were initiated at the point of distension. These results suggest that intrinsic inhibitory neurones are present in the caecum and may be triggered by distention. The possible role of these inhibitory neurones in the emptying and filling of the caecae is considered.

Contractions of the caudal region of the oesophagus of the cat.

1. The motility of the most caudal part of the oesophagus has been investigated in cats which were decerebrated, had the whole of the central nervous system pithed or were anaesthetized with chloralose.2. Contractions of the most caudal region of the oesophagus were evoked by its stretch and the presence in it of HCl. These reactions were obtained in all types of preparations used.3. In decerebrate preparations oesophageal contractions occurred in response to the introduction of acid into the stomach. These were not obtained after the vagus nerves had been cut.4. Slight degrees of gastric distension stimulated oesophageal contractions, greater distension was inhibitory.5. Both reductions in oesophageal activity and contractions of the oesophagus were obtained with different parameters of stimulation of efferent vagal fibres.6. Excitatory and inhibitory effects on the oesophagus were obtained from stimulation of the central end of the vagus nerves cut in the abdomen or in the neck.7. In totally pithed preparations of cats stretch of one region of the oesophagus was found to modify the activity of a distant region of the oesophagus cranial or caudal to the site of distension.8. The reactions of the caudal oesophagus were abolished by atropine.9. The importance of vago-vagal reflexes in the modification of basically direct oesophageal responses has been discussed.