Distension Volume Research Articles

The effect of distension of the stomach on peripheral blood flow in anaesthetized pigs.

The present study was undertaken in anaesthetized pigs to determine the primary reflex effects of gastric distension on the peripheral circulation. Changes in blood flow in the splenic, superior mesenteric, left renal and left external iliac arteries were assessed using electromagnetic flowmeters during distension of a balloon in the stomach, performed at constant aortic blood pressure and heart rate, with 0.6 l of Ringer solution (mean gastric transmural pressure of about 12 mmHg). In fourteen pigs, a decrease in splenic, renal and iliac flows and variable changes in mesenteric flow were obtained. A decrease in mesenteric flow and more marked decreases in the other flows occurred in response to the distension after the administration of propranolol or butoxamine. In five pigs, the vasoconstrictive responses were graded by step increments in gastric distending volume from 0.4 to 0.8 l. The above responses were abolished by the administration of phentolamine (eight pigs) and by bilateral cervical vagotomy (six pigs). The results showed that innocuous distension of the stomach in anaesthetized pigs reflexly caused vasoconstriction in the splenic, renal and iliac vascular beds; vasoconstriction also occurred in the mesenteric vascular bed but only after beta-blockade. These reflex responses were mediated by sympathetic mechanisms which involved both alpha and beta vascular adrenoceptors and their afferent limb was in the vagal nerves.

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.

Methods for studying intestinal sensitivity and compliance: in vitro studies of balloons and a barostat

The aim of this study was to compare in vitro various methods for recording intestinal sensitivity and compliance. Relationships between volume and pressure were determined in segments of penrose tubing and pig gut ("artificial intestine') using pressure increments of 2 mmHg (0-24 mmHg). We tested two direct methods of distension of the entire segments (by syringe inflation and the Mayo barostat); we also used three different balloon devices for indirect distension (a 10 cm polyethylene barostat bag, a 10 cm latex condom balloon and a 6 cm latex condom balloon). Maximal distending diameters of the recording systems were measured by injecting from 0 to 160 mL of air. The elastic properties of the balloons were also tested by distensions in air and in rigid tubes. All recording systems accurately detected a lesser compliance of the penrose drain as compared to pig gut. In absolute terms, only the compliance measured with a polyethylene barostat bag distended with a syringe was not different from the compliance of the segment as measured directly. The bellows of our barostat and the latex balloons had significant intrinsic compliances which interfered with the recorded pressure-volume curves. On the other hand, highly compliant plastic bags recorded most faithfully the compliance of artificial gut and that of non-compliant rigid tubes. For comparable volumes of distension, external diameters were larger with the 6 cm latex balloon than with the 10 cm latex balloon or the 10 cm polyethylene barostat balloon. A polyethylene bag distended with a non-compliant air injector (syringe) reflected most accurately the pressure-volume relationships of tubular structures. The different maximal diameters assumed by the three distending devices may explain, in part, why lower volumes of distension are required to elicit symptoms with smaller distending balloons in vivo.

Gradient of pressure and time between proximal anal canal and high-pressure zone during internal anal sphincter relaxation

The normal response to rectal distention is a relaxation of the proximal anal canal (PAC). We hypothesized that this mechanism would require a gradient of pressure and time to preserve continence. Sixteen volunteers (10 male), mean age, 41.5 (range, 24-60) years, were studied using an eight port axial catheter with a compliant balloon at its tip. Relaxation was induced by a small volume of rectal distention (15-30 ml of air) and was recorded until recovery of resting anal pressure (RAP). Duration of relaxation was measured until recovery of RAP. Amplitude of relaxation was determined between RAP before rectal distention (RAP-BR) and pressure at the point of maximum relaxation (RAP-PMR). Gradient of pressure was determined by comparing RAP-PMR in the high-pressure zone (HPZ) and PAC. Contraction in the distal anal canal was interpreted as external anal sphincter contraction (EASC) and was compared with RAP-PMR in the HPZ. Relaxation was significantly greater in PAC than in HPZ (50 vs. 36 percent; P = 0.001). RAP-PMR was significantly higher in HPZ than in PAC (30.7 vs. 12.6 mmHg; P = 0.001). EASC was observed in six patients and did not show significant difference with RAP-PMR in HPZ (39.7 vs. 36.3 mmHg; not significant). Relaxation began at the same time in all levels but lasted significantly longer in PAC compared with HPZ (13.5 vs. 9.4 sec; P = 0.003). Anal relaxation induced by small volume rectal distention involves a gradient in the pressure and time of relaxation between PAC and the HPZ.

Distal rectoanal excitatory reflex: a reliable index of pudendal neuropathy?

Denervation of the extrinsic anal sphincter and pudendal neuropathy are confirmed by electrophysiologic or electromyographic testing, techniques that may not be available universally and require special equipment and training. A simple manometric test that is easy to perform and complements existing studies was performed to confirm pudendal neuropathy. Fourteen patients with excessive defecatory straining and 30 patients with idiopathic fecal incontinence were studied by electrophysiology and balloon reflex manometry. Pudendal nerve terminal motor latency (PNTML) and rectoanal excitatory reflex were evaluated for abnormalities. Results were compared with 20 controls who had no anorectal complaints and who had similar testing performed. In controls, PNTML was normal in all but one person. Rectoanal excitatory reflex could be elicited in all controls with either 20 or 40 ml of air. Four different types of balloon reflex responses were observed in patient groups: diminutive excitation, delayed excitation, excitation at high volume of distention only, and absent excitation. Ten patients with fecal incontinence had normal PNTML but abnormal distal excitatory reflex, 5 patients had abnormal PNTML but normal distal excitatory reflex, and 15 patients had both PNTML and excitatory reflex that were abnormal. In patients with excessive defecatory straining, results of both tests were abnormal in six patients, and eight patients had abnormal excitatory reflex but normal PNTML. Pudendal neuropathy may result in abnormalities of excitatory reflex morphology or other characteristics. Abnormal distal excitatory reflex may complement electrophysiologic findings or may serve as a suitable alternative to confirm pudendal neuropathy in centers where facilities for formal testing are not available.

Influence of bradykinin in gastrointestinal disorders and visceral pain induced by acute or chronic inflammation in rats.

This work investigated the role of bradykinin in viscerosensitivity before and during inflammation in two models of visceral pain induced by rectal distension (RD) or "abdominal distension" (AD) in rats. RD induced both inhibition of colonic motility and an increase of abdominal spike bursts. Bradykinin receptor antagonist, Hoe 140 did not affect any of the RD-induced responses. After TNB-induced rectal inflammation, colonic inhibition and the number of abdominal contractions were enhanced. Hoe 140 selectively reduced the abdominal response to the highest distension volume, without affecting the colonic response. In AD group, acetic acid inhibited gastric emptying and increased the number of abdominal contractions, whereas the same volume of saline did not affect any of the responses. Before inflammation, Hoe 140 (1-5 mg/kg, intraperitoneally) did not affect per se abdominal and gastric emptying responses; in contrast, at 5 mg/kg, intraperitoneally, it reduced significantly (P < 0.05) both acetic acid-induced responses. We conclude that bradykinin is involved in viscerosensitivity changes related to abdominal and rectal distension in inflammatory conditions.

The effect of octreotide on human gastric compliance and sensory perception.

Somatostatin or its analogue octreotide (OCT) has previously been shown to modulate gastric emptying, intestinal motor activity and visceral sensation. In the current study we sought to determine the effect of a single dose of OCT (1.25 micrograms kg-1 s.c.), which has previously been shown to have both motor and sensory effects, on proximal gastric compliance and on conscious perception of gastric distention. Gastric distention was performed in 13 healthy male volunteers, by either slow ramp distention (60 ml min-1) or by intermittent pressure steps (phasic distention; 4-20 mmHg) using an electronic distention device. Compliance curves (pressure-volume relationship), and thresholds for innocuous (fullness) and noxious sensations (discomfort, pain) were determined following vehicle or OCT injection. OCT consistently and significantly reduced the rate of the gastric accommodation reflex by 50%, resulting in a reduced compliance at distention pressures greater than 10 mmHg during phasic distention. In contrast, no effect was observed on the compliance curve obtained during ramp distention. OCT selectively increased the threshold for fullness during both ramp and phasic distention. During phasic distention, OCT decreased the volume thresholds for noxious (pain) sensations experienced at volumes greater than 300 ml, without affecting the corresponding pressure threshold. These findings suggest that at low distension volumes, OCT in the dosage used has a direct inhibitory effect on afferents mediating innocuous gastric sensations. The hyperalgesic effect observed during phasic distention may be secondary to OCT's inhibitory effect on the gastric accommodation reflex.

Is the afferent pathway from the rectum impaired in children with chronic constipation and encopresis?

Background & Aims: Rectal sensations to balloon distention are impaired in children with chronic constipation and encopresis. The impairment of rectal sensation, which is often persistent and is related to nonrecovery, could be caused by a defect in the visceral afferent pathways. The aim of this study was to test whether the afferent pathway from the rectum is impaired in children with constipation and encopresis. Methods: Fifteen healthy children and 15 children with constipation and encopresis were studied. Cerebral evoked potentials (EPs) were studied by averaging results of 100 rectal distentions, which used 10, 20, and 30 mL air. EPs were recorded from Cz′ to Fz. Results: Two different types of EPs were recorded in each control subject and each child with constipation and encopresis. One EP had an early onset and showed multiple positive and negative peaks. The other EP had a much later onset and was triphasic. Early-onset EPs were recorded with significantly smaller distention volumes than the late-onset EPs. N1 and P2 latencies of the early-onset EPs and NI, PI, and NII latencies of the late-onset EPs were significantly prolonged in children with constipation and encopresis compared with controls. Conclusions: The prolonged latencies suggest a defect in the afferent pathway from the rectum in children with chronic constipation and encopresis.

Gastric tone determines the sensitivity of the stomach to distention

Background/Aims: Whether meal-related symptoms such as postcibal epigastric fullness and discomfort are caused by hypotonic gastric expansion or gastric hypertension is unknown. This study investigated whether symptoms in healthy individuals in response to gastric distention are produced by gastric expansion or by an increase in intragastric pressure. Methods: Increasing gastric distentions (for 5 minutes at 5-minute intervals) at fixed pressure levels (in 2-mm Hg increments) and at fixed volume levels (in 200-mL increments) were performed in 10 healthy subjects per group; perception was measured on a 0–6 scale. Distentions were performed during intravenous infusion of saline (basal) and during gastric relaxation by intravenous administration of glucagon (4.8-μg/kg bolus plus 9.6 μg · kg −1 · h −1 infusion). Results: The same distending pressures tested produced 30% ± 9% larger intragastric volumes and 80% ± 44% higher perception scores when the stomach was relaxed by glucagon ( P < 0.05 vs. basal for both). In contrast, the same distending volumes tested produced 25% ± 7% lower intragastric pressures and 21% ± 12% lower perception scores when the stomach was relaxed ( P < 0.05 vs. basal for both). Conclusions: Epigastric symptoms in response to gastric distention are influenced by both the intragastric pressure and the intragastric volume.

Effect of topical anaesthesia on oesophageal sensory and motor function in healthy subjects

Abstract Oesophageal hyperalgesia was demonstrated in the non‐cardiac chest pain syndrome and suggests an altered perception of visceral stimuli in these patients. Data on oesophageal sensory function and its pharmacological manipulation, however, are fragmentary.Using a randomized, double‐blind, placebo‐controlled, cross‐over design, ten healthy male volunteers were manometrically examined for the effects of topical oesophageal anaesthesia with benzocaine 0.75% on (1) oesophageal perception of graded intra‐luminal balloon distension, (2) oesophageal compliance and primary motility, and (3) rectal perception of graded intraluminal balloon distension.It was demonstrated that topical benzocaine significantly increased oesophageal perception thresholds for intraluminal distension (P &lt; 0.03), irrespective of them being correlated to distension volume or distension pressure. The level of first sensation increased from 4.3 ml (SD 2.8) and 24.8 mmHg (SD 9.1) to 7.4 ml (SD 4.4) and 32.1 mmHg (SD 8.3), respectively; pain perception increased from 11.O ml (SD 4.5) and 30.9 mmHg (SD 8.9) to 14.5 ml (SO 5.1) and 38.3 mmHg (SD 10.2), respectively. In contrast, oesophageal compliance, primary oesophageal motility and rectal perception were not altered.It was concluded that topical anaesthesia decreases visceral sensitivity of the oesophagus to mechanical distension by action on intramural nervous afferents. It does not affect oesophageal motor function, nor does it exert systemic analgesic effects.

A nonlinear mathematical model for the development and rupture of intracranial fusiform aneurysms.

Laplace's law, which describes a linear relation between the tension and the radius, is often used to characterize the mechanical response of the aneurysm wall to distending pressures. However, histopathological studies have confirmed that the wall of the fully developed aneurysm consists primarily of collagen and is subject to large increases in tension for small increases in the radius, i.e., a nonlinear relationship exists between the tension within the aneurysm wall and the radius. Thus, a nonlinear version of Laplace's law is proposed to accurately describe the development and rupture of a fusiform saccular aneurysm. The fusiform aneurysm was modelled as a thin-walled ellipsoidal shell with a major axis radius, Ra, minor axis radius, Rb, circumferential tension, S0, and meridional tension, S phi, with phi defining the angle from the surface normal. Using both linear and nonlinear models, differential expressions of the volume distensibility evaluated at 90 degrees were used to determine the critical radius of the aneurysm along the minor axis from S0 and S phi in terms of the following geometric and biophysical variables; A, elastic modulus of collagen; E, elastic modulus of the aneurysm (elastin and collagen); t, wall thickness; P, systolic pressure; and Ra. For typical physiological values of A = 2.8 MPa, E = 1.0 MPa, T = 40 microns, P = 150 mmHg, and Ra = 4Rb, the linear model yielded critical radii of 4.0 mm from S phi and 2.2 mm from S0. The resultant critical radius was 4.56 mm. Using the same values, the critical radii from the tension components of the nonlinear model were 3.5 mm from S phi and 1.9 mm from S0.(ABSTRACT TRUNCATED AT 250 WORDS)

Coordinated activity of the new “rectum” and anal sphincter after sphincter-saving resection of the rectum for colitis or carcinoma

The aim of this study was to determine whether coordinated activity exists across a stapled enteroanal anastomosis. Twenty-nine patients were studied for a median of one year after complete excision of the rectum and stapled enteroanal anastomosis; 12 patients underwent low anterior resection with coloanal anastomosis for carcinoma, and 17 patients underwent restorative proctocolectomy with ileoanal anastomosis. Maximum anal resting pressures were slightly lower after coloanal anastomosis than after ileoanal anastomosis [median range, 56 (11-60) cm H2O, cf 69 (40-107) cm H2O, P = NS]. During distention of the neorectum, anal sphincter pressures at 2.5, 1.5, and 0.5 cm from the anal verge were significantly lower after coloanal anastomosis compared with after ileoanal anastomosis (P < 0.01 at each station). The volume of neorectal distention required to produce maximal inhibition of the anal sphincter was significantly less after coloanal anastomosis at 50 (range, 20-60) ml of air than after ileoanal anastomosis at 240 (range, 100-420) ml of air (P < 0.01). Minor fecal leakage and urgency of bowel action were significantly more common after coloanal anastomosis (P < 0.01). Alterations in the dynamic response of the anal sphincter to distention of the neorectum may explain why the clinical results were better after ileal pouch-anal anastomosis than after coloanal anastomosis.

The effect of distension of the stomach on coronary blood flow in anaesthetized pigs

The present study was undertaken in anaesthetized pigs to determine whether distension of the stomach reflexly affects coronary blood flow. Experiments were performed on 17 pigs anaesthetized with ketamine and sodium pentobarbitone and artificially ventilated. Coronary blood flow was measured with an electromagnetic flowmeter positioned around the origin of the left circumflex coronary artery. The stomach was distended by injecting 0.8l warm Ringer solution into a balloon positioned within the stomach (mean gastric transmural pressure of about 13 mm Hg). Changes in aortic blood pressure and heart rate were prevented by a pressurized reservoir connected to the left femoral artery and by atrial pacing respectively. Distension of the stomach always caused a decrease in mean coronary blood flow. In five pigs, the magnitude of the decrease in coronary blood flow was graded by step increments in the gastric distending volume from 0.6l to 1l. The response of coronary blood flow was not affected by the administration of atropine (12 pigs), while it was abolished by the administration of bretylium tosylate (eight pigs) and by bilateral vagotomy (eight pigs; four cervical, four subdiaphragmatic vagotomy). These results show that innocuous distension of the stomach in anaesthetized pigs reflexly decreases coronary blood flow. This reflex response is mediated by sympathetic effects and its afferent limb involves the vagal nerves.

The effects of oesophageal distension on diaphragm and laryngeal muscle activity in the anaesthetized cat.

The electromyographic (EMG) activities of diaphragm and laryngeal muscles were recorded during oesophageal distension in anesthetized cats. The responses to distension of the thoracic oesophagus differed from those evoked by distension of the cervical oesophagus. The crural component of the diaphragm (CD) was inhibited by distension of the thoracic oesophagus; distension of the cervical oesophagus did not affect CD EMG. Thyroarytenoid (TA) muscle EMG increased markedly and consistently in response to distension of the cervical oesophagus. Distension of the thoracic oesophagus only produced statistically significant increases in TA EMG with high distending volume (10 ml) at the level of the gastro-oesophageal junction. The main abductor of the vocal cords, the posterior cricoarytenoid (PCA) was either unchanged or decreased by oesophageal distension. The electrical activities of left paratendinous diaphragm, left costal diaphragm, internal intercostal and external intercostal muscles remained unchanged. The entire pattern would appear to constitute a means to aid passage of a bolus into the stomach, and simultaneously guard the respiratory tract from reflux or aspiration.

Blood flow, volume, and transit time in the pulmonary microvasculature using laser-Doppler.

Capillary transit time is determined by the ratio of capillary volume to flow rate. Exercise-induced hypoxemia is thought to occur because of the short transit time of erythrocytes in capillaries. The effect of flow rate on capillary volume (recruitment vs. distension) is controversial. In a perfused left lower lobe preparation in canine lungs, we used laser-Doppler flowmetry (model ALF21R) to monitor changes in blood flow, volume, and transit time in the microvasculature near the subpleural surface. Changes in total flow, blood volume, and total transit time (tt) were also measured. The results showed that microvascular volume approached maximum when flow rate was at resting value (0.4 l/min) and pressure in the pulmonary artery was > 6 mmHg relative to the level of the capillaries. In contrast, the total blood volume increased gradually over a wide range of flow rates. When flow increased 4.2 times (from 155 to 650 ml/min), tt decreased from 7.32 to 3.53 s; meanwhile, microvascular flow increased from 6.0 to 12.7 units and microvascular transit time decreased from 3.14 to 1.81 units. The changes in microvascular volume and transit time were essentially independent of whether the venous pressure was higher or lower than alveolar pressure. At very high flow (6-10 times resting value), tt fell gradually to approximately 1 s. Direct monitoring of transit time with the laser-Doppler also revealed a gradual decline in microvascular transit time as flow rate increased from 2 to 10 times the normal flow. (ABSTRACT TRUNCATED AT 250 WORDS)

Nutrient ingestion increases rectal sensitivity in humans

To determine the effect of nutrient ingestion on rectal perception thresholds (first sensation, consistent urge to defecate, pain), rectosigmoid balloon distentions were performed with a computerized automated pump in eight healthy volunteers (four males, four females, 31.6 ± 6.02 years). Two measurements of rectal balloon distention were performed on 2 separate days. Day 1 served as a control condition with no meal. On day 2 the subjects received a 600 kcal liquid meal. On the control day, determination of perception thresholds was performed two times with a 10-min break between measurements. On the experimental day, threshold determinations were made before and after the ingestion of the liquid standard meal. The order of the experimental days was counterbalanced. Distention volumes at the urge to defecate and the pain threshold (maximum tolerable volume) were significantly reduced following the meal. The average change from pre- to postprandial measurements of the threshold for urge to defecate was −20.55 ± 4.22% and for the maximum tolerable volume it was −16.09 ± 4.4%. These results extend data previously reported from animal studies using similar experimental methods.

The trigger for rectal filling sensation

In order to evaluate whether rectal volume, weight or pressure is the main trigger for rectal sensation, their respective values were determined at each of the rectal filling sensation thresholds (first, constant, urge, maximum) in 12 adult control subjects. The rectal balloon was filled at 60 ml/min in sitting position using water (twice), air and mercury consecutively. Pressure values were corrected for the elastic properties of the balloon, while the volume of inflated air was recalculated taking into account the prevalent rectal pressure and temperature. The results obtained using water, air and mercury demonstrated a constant relationship between a given rectal sensation level and the pressure recorded in the distending balloon, but not its volume or weight. Pressure values recorded at each sensation level were constant during repeated determinations of rectal sensation, the volume of rectal distension increased, probably because the rectum had already been dilated by previous testing. Balloon distension using air with the patient in the lateral position were found to be most practical for routine evaluation of rectal sensation. It is therefore concluded that any disturbance of rectal sensation will be reflected by changes in pressure and not by changes in the volume needed to produce a given sensation level. The location of the receptors involved has to be elucidated, but it seems that the pelvic floor can be excluded since the weight of the rectal contents was not related to sensation.

Gastrointestinal hemodynamics during compensation for hemorrhage and measurement of Pmcf

To quantify the degree of autonomic reflex control of the gastrointestinal vasculature, we studied the responses to a 10-ml/kg hemorrhage or transfusion and autonomic blockade in fentanyl- and pentobarbital-anesthetized dogs. The active total blood volume was estimated by indocyanine green dilution. Transfusion and hemorrhage did not significantly change gastrointestinal vascular compliance [1.82 +/- 0.68 (SD) ml/mmHg], but autonomic blockade with hexamethonium and atropine increased it by 0.57 +/- 0.37 ml/mmHg. Neither hemorrhage nor autonomic blockade significantly changed gastrointestinal vascular resistance from its control value of 10.8 +/- 4 mmHg.ml-1.min.kg body wt, but transfusion reduced it by 3.0 +/- 1.2 mmHg.ml-1.min.kg body wt. The ratio of gastrointestinal vascular resistance to total peripheral resistance was not significantly changed, however. We conclude that vascular compliance and resistance of the gastrointestinal bed are minimally influenced by the autonomic nervous system under the conditions studied. Portal pressure and flow measurements (transit-time ultrasound) during the above maneuvers were also combined with estimations of mean circulatory filling pressure (Pmcf) to test the hypothesis that, when the heart is stopped to measure Pmcf, portal pressure equals central venous pressure (Pcv) and hence that portal flow is zero. Seven seconds after the heart was stopped, portal venous pressure (Ppv) remained 0.83 +/- 0.78 mmHg higher than Pcv and portal flow decreased to only 25% of its control value. However, gastrointestinal compliance times (Ppv-Pcv), an estimate of the extra distending volume, was only 0.07 +/- 0.07 ml/kg body wt. Thus we conclude that the error in estimating Pmcf, given this (Ppv-Pcv) difference, is physiologically insignificant.

Cerebral potentials evoked by rectal distention in humans

The afferent pathways from the rectum can be stimulated and studied after mechanical distention of the rectum. We studied the rectum-brain axis in 24 healthy young adults. The rectum was stimulated with a rectal balloon using inflation volumes of 10 ml and 30 ml air at a stimulation frequency of 0.167 Hz. Additional studies were carried out with 20 ml distention volumes, random stimulation frequency, and stimulation rates of 0.08 Hz and 0.017 Hz. We found two different cortical EPs. An early onset EP was present in 21 of the 24 subjects. P1 latency shortened significantly with increasing distention volumes, but peak amplitudes did not change significantly with larger distention volumes. A late onset EP was present in all subjects with NI latency of 210 ± 15 msec, PI latency of 316 ± 24 msec, and NII latency of 444 ± 34 msec. The different EPs could be due to stimulation of two different visceral afferent pathways which are present in the same individual, due to stimulation of two different fiber populations or due to simultaneous stimulation of afferents in surrounding structures. EP recording after rectal stimulation might be useful in future studies of patients with abnormal rectal sensation.

Central and peripheral effects of CCK receptor antagonists on satiety in dogs.

The role of cholecystokinin (CCK) as a central and peripheral satiety factor was studied using the CCK-B (L-365,260) and CCK-A (MK-329) receptor antagonists in esophageal-fistula dogs. Suppression of feeding was induced by either balloon gastric distension or small bowel nutrient infusion and was measured as the volume sham fed. Intracerebroventricular L-365,260 abolished satiety behavior from gastric distension (volume sham fed 2,667 +/- 211 ml vs. vehicle alone 1,217 +/- 446 ml, P < 0.05) but not small bowel infusion. Intravenous MK-329 abolished satiety behavior from small bowel infusion (volume sham fed 1,900 +/- 521 ml vs. vehicle alone 210 +/- 198 ml, P < 0.05) but not from gastric distension. The volume sham fed after intracerebroventricular MK-329 with balloon gastric distension or small bowel infusion did not differ from control. These results suggest that, in the brain, CCK is a physiological mediator of satiety behavior from gastric distension but not small bowel nutrients and, in the periphery, CCK is a physiological mediator of satiety behavior from small bowel nutrients but not gastric distension.