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F Azpiroz

Publications and source records attributed to F Azpiroz.

At least 37 records · Page 2Linked to original sources

Selective dysfunction of mechanosensitive intestinal afferents in irritable bowel syndrome.

BACKGROUND/AIMS: Experimental studies have shown gut hypersensitivity in irritable bowel syndrome. The aim of this study was to determine whether heightened perception of gut distention in irritable bowel syndrome is related to either decreased gut compliance, altered mechanosensitive afferents, or nonspecific sensory dysfunction. METHODS: In 17 patients with irritable bowel syndrome and 15 healthy controls, stimulus-related perception of (1) intestinal balloon distentions, (2) transmucosal electrical nerve stimulation (15 Hz, 100 microseconds), and (3) somatic transcutaneous electrical nerve stimulation (100 Hz, 100 microseconds) was measured. Individual stimuli of 1-minute duration were randomly applied at 5-minute intervals. RESULTS: Patients tolerated smaller intestinal volumes than controls (33 +/- 3 mL vs. 43 +/- 4 mL, respectively; mean +/- SE; P < 0.05), whereas both intestinal compliance and perception of transmucosal electrical nerve stimulation were normal (patients tolerated 58 +/- 5 mA and healthy subjects tolerated 69 +/- 5 mA). Interestingly, patients perceived both stimuli more diffusely than controls; 48% +/- 9% distentions and 52% +/- 9% electrical stimuli were perceived over more than one abdominal region vs. 21% +/- 9% and 18% +/- 6%, respectively, in controls (P < 0.05 for both). In contrast to gut distentions, patients showed higher tolerance of somatic stimuli than controls (68 +/- 7 mA vs. 42 +/- 6 mA, respectively; P < 0.05). CONCLUSIONS: Patients with irritable bowel syndrome show selective hypersensitivity of intestinal mechanosensitive pathways associated with a nonspecific, probably central dysfunction of viscerosomatic referral.

Abdomen↗

The sympathetic nervous system modulates perception and reflex responses to gut distention in humans.

BACKGROUND/AIMS: Intestinal distention induces perception and gut reflexes via sympathetic and vagal pathways, but the modulatory mechanisms of such responses remain obscure. The aim of this study was to determine the effects of sympathetic nervous activity on sympathetic and vagal reflexes as well as on intestinal and somatic perception. METHODS: In 9 healthy volunteers, proximal duodenal distentions were produced in 4-mL increments and hand transcutaneous electrical nerve stimulation was produced in 3-mA increments. Increasing stimuli of 1-minute duration were randomly performed at 10-minute intervals both with and without sympathetic activation (induced by means of lower body negative pressure). Intestinal and somatic perception was scored by specific questionnaires; vagal enterogastric and sympathetic intestinointestinal relaxatory reflexes were simultaneously measured by gastric and distal duodenal barostats. RESULTS: Sympathetic activation significantly heightened perception of intestinal distention without modifying perception of somatic stimuli (perception scores increased by 41% and -2%, respectively). The reflex responses to duodenal distention significantly increased during sympathetic activation both in the stomach and in the intestine (relaxation increased by 91% and 69%, respectively; P < 0.05 for both). CONCLUSIONS: Activation of the sympathetic nervous system selectively increases visceral but not somatic sensitivity and enhances both vagally and sympathetically driven reflexes in the gut.

Adult↗

Perception and reflex responses to intestinal distention in humans are modified by simultaneous or previous stimulation.

BACKGROUND & AIMS: Intestinal reflexes induced by distention in dogs are facilitated by either simultaneous or previous distentions. The aim of this study was to determine whether these phenomena also modulate the responses to intestinal distention, particularly perception, in humans. METHODS: Perception and intestinal relaxation were measured in 11 healthy subjects in response to increasing jejunal balloon distentions tested (by stimulus-response trials) alone, as control, and with conditioning distentions applied either simultaneously, immediately (10 seconds) before at the same site, or immediately before and 5 cm distant. In 8 additional subjects, the effect of prolonged (90-minute) conditioning distention was tested. RESULTS: Conditioning had more pronounced effects on perception than on intestinal reflexes. Perception of intestinal distention increased (by 84 +/- 47%; P < 0.05) when a simultaneous distention was applied nearby. By contrast, perception decreased (by 38 +/- 12%; P < 0.05) when a previous distention was applied at the same but not at an adjacent site. Prolonged intestinal distention elicited remarkably stable perception during a 90-minute period. The effects of conditioning were unrelated to intestinal compliance because it remained unchanged. CONCLUSIONS: In humans, temporospatial interactions of gut stimuli activate modulatory phenomena that determine the perception intensity of the stimuli.

Adult↗

Control of gastric emptying by gastric tone.

During ingestion of food, the stomach relaxes to accommodate the meal and, subsequently, a progressive gastric contraction parallels gastric emptying. Intestinal nutrients trigger feedback relaxatory mechanisms that regulate gastric tone and, hence, the nutrient load delivered into the small intestine. This regulation of gastric tone is mediated, at least in part, via the vagus. Defective gastric tone is associated with impaired gastric emptying, as seen in patients with postsurgical gastroparesis. However, increased intragastric pressure, corresponding with defective gastric accommodation, induces abdominal symptoms, but does not alter the gastric emptying pattern. These data indicate that gastric emptying is controlled by complementary mechanisms: gastric tone exerts an emptying force, but gastric outlet resistance is also an important regulator.

Animals↗

Selective gastric hypersensitivity and reflex hyporeactivity in functional dyspepsia.

BACKGROUND/AIMS: We have previously shown that patients with functional dyspepsia are hypersensitive to gastric distention. The aim of this study was to establish whether this sensory disturbance was confined to the stomach and whether it was associated with gut reflex dysfunction. METHODS: In 10 selected patients with dyspepsia and 12 healthy controls, perception and gut reflex responses to gastric distention, duodenal distention, and somatic stimulation were measured. Standardized distentions at fixed pressures were performed by gastric and duodenal barostats. Perception was scored by a detailed symptom questionnaire; gut reflex responses were measured as isobaric volume changes by each barostat. Somatic transcutaneous electrical nerve stimulation was produced on the hand. Individual stimuli (2-minute duration) were randomly applied at 10-minute intervals in stepwise increments in search of the respective threshold for discomfort. RESULTS: Patients with dyspepsia had gastric hypersensitivity to distention (discomfort threshold at 6.4 +/- 0.4 mm Hg vs. 8.3 +/- 0.6 mm Hg in controls; mean +/- SE; P < 0.05), whereas duodenal and somatic sensitivity was normal. Furthermore, patients with dyspepsia explicitly recognized their clinical symptoms in all gastric but only in 58% +/- 12% of the duodenal distention trials. In addition, patients with dyspepsia showed defective gastric relaxatory responses to duodenal distention (68 +/- 30 mL gastric expansion vs. 239 +/- 12 mL in controls; P < 0.05). CONCLUSIONS: Patients with dyspepsia are selectively hypersensitive to gastric distention; this sensory dysfunction is associated with impaired reflex reactivity of the stomach.

Adult↗

Somatic stimulation reduces perception of gut distention in humans.

BACKGROUND/AIMS: Perception of gut symptoms may depend on visceral sensory modulation, but the mechanisms are poorly understood. Based on somatosensory data, we hypothesized that somatic stimulation modulates perception of gut stimuli. METHODS: Perception and gut reflexes were measured in 8 healthy subjects in response to increasing gastric and duodenal distentions (stimulus-response trials) performed alone or with simultaneous application on the hand of either low (just perceivable) or high (nonpainful) transcutaneous electrical nerve stimulation (100 Hz, 100 microseconds). Fixed pressure distentions were performed in stepwise increments by gastric and duodenal barostats to determine the respective thresholds for discomfort. Perception was measured by a questionnaire, and gut reflex responses were measured as isobaric volume changes by the barostats. Individual stimuli of 2 minutes' duration were randomly applied at 10-minute intervals. RESULTS: Somatic stimuli increased the tolerance to gut distention, and this effect was more pronounced with high stimuli. The gastric threshold for discomfort was 7.3 +/- 0.5 mm Hg with high stimuli vs. 5.5 +/- 0.2 mm Hg without stimuli, and the duodenal discomfort threshold was 15.5 +/- 1.5 mm Hg with high stimuli vs. 13.5 +/- 1.4 mm Hg without stimuli; P < 0.05 for both. Somatic stimuli modified neither basal gut tone nor the relaxatory duodenogastric reflex induced by duodenal distention (gastric expansion by 203 +/- 48 mL with high stimuli and 208 +/- 73 mL without stimuli). CONCLUSIONS: Somatic stimulation reduces perception of gut distention without interfering with local and reflex gut responses.

Adult↗

Relations among intragastric pressure, postcibal perception, and gastric emptying.

Our aims were to investigate, first, the relationship between gastric tone (measured with a barostat) and gastric emptying (measured by radioscintigraphy with and without barostat) and, second, to determine the effect of a symptomatic intragastric pressure increment on gastric emptying. In 16 healthy subjects we quantified simultaneously gastric tone, emptying, and perception at two different intragastric pressure levels: 2 mmHg (low pressure) or 8 mmHg above intra-abdominal pressure (high pressure). At the low intragastric pressure level, ingestion of the meal induced an additional expansion in intragastric volume of 285 +/- 50 ml (P < 0.001), which reflected a gastric accommodative relaxation. At the high pressure level, intragastric volume expanded further, but neither low nor high pressure levels had significant effects on solid emptying. Interestingly, low and high pressure levels produced a similar, modest but significant, acceleration of liquid emptying (17 +/- 5 and 17 +/- 4%, respectively). However, although the low pressure was largely unperceived (score 1.0 +/- 0.5; NS), the high pressure level produced significant symptomatic perception (score 2.5 +/- 0.9; P < 0.05 vs. low pressure). We conclude that 1) gastric accommodation to a meal prevents volume-dependent wall tension increments and 2) the stomach adapts to increments in postcibal intragastric pressure by a limited acceleration of liquid emptying, but wall stress triggers a symptomatic alert mechanism.

Adult↗

Symptomatic responses to stimulation of sensory pathways in the jejunum.

We hypothesized that intestinal afferent pathways inducing perception may be selectively activated by transmucosal electrical nerve stimulation, without disruption of the intrinsic myoelectrical rhythm. Hence, in 12 healthy subjects we measured perception (by a questionnaire) and jejunal slow wave activity (by electromyography), and we randomly applied for 1 min at 5-min intervals graded electrical (15 Hz, 100 microseconds) and mechanical stimuli (balloon distension) in the jejunum up to the respective discomfort threshold. Electrical and mechanical stimuli induced dose-related perception; the perception and discomfort thresholds were 39 +/- 7 and 63 +/- 6 mA and 31 +/- 3 and 49 +/- 5 ml for electrical and mechanical stimuli, respectively. More than one-half of electrical stimuli elicited clinical-type symptoms (abdominal pressure, fullness, colicky or sharp sensation) similar to those induced by mechanical stimuli; the remaining electrical stimuli (38 +/- 10%) induced paresthesia or flutterlike sensation. Similar types of symptoms were perceived with weak and strong stimuli. Jejunal slow wave activity (11.3 +/- 0.4 cycles/min) was not modified by either stimuli. We conclude that activation of intestinal sensory pathways, either by transmucosal nerve stimulation or via mechanoreceptors, induces a similar dose-related symptomatic response, without interfering with the intrinsic myoelectrical activity.

Adult↗

Duodenal mucosal resistance to intraluminal acid in the rat: role of adaptive cytoprotection.

The duodenal mucosa is normally challenged by intermittent exposure to acid because of periodic gastric emptying. We studied the mechanisms of duodenal adaptation to acid in anesthetized rats. A polyvinyl chloride tube passing through a ligated pylorus was used for duodenal pulse instillations of 1 mL of saline or acid (100 or 400 mumols HCl) at 30-minute intervals. Duodenal lesions were blindly assessed using a combined macroscopic and histological score. Mucosal damage after exposure to saline or 100 mumols HCl was negligible in intact, vagotomized, and indomethacin-pretreated rats, whereas 400 mumols induced noticeable macroscopic and microscopic lesions. Interestingly, in intact and vagotomized rats, previous exposure to a 100-mumols HCl bolus significantly prevented mucosal damage by a subsequent 400-mumols bolus. This effect was not observed in indomethacin-pretreated rats. In these rats, however, intraduodenal instillation of exogenous 16,16-dimethyl prostaglandin E2 (16,16-dm-PGE2) prevented the damage induced by 400 mumols of HCl. A second protocol investigated the luminal release of bicarbonate and PGE2 in response to intraduodenal perfusion with 100 mumols of HCl. Duodenal bicarbonate release was stimulated by acid in all groups, whereas the release of PGE2 increased in intact and vagotomized rats but not in the indomethacin-pretreated group. In summary, these data suggest that adaptive cytoprotection plays a significant role in protecting the duodenal mucosa from acid. Vagal innervation and bicarbonate release do not appear to be as critical as cyclo-oxygenase activity for this mechanism.

16,16-Dimethylprostaglandin E2↗

Sensorial and intestinointestinal reflex pathways in the human jejunum.

Using an intestinal barostat that maintains a constant pressure within an air-filled bag (12 cm long), the authors have previously shown reflex changes in intestinal tone induced by distention. The aim of this study was to investigate the sensitivity and the responsiveness to such reflexes along the jejunum. Eight healthy volunteers were studied using two barostats operating simultaneously in the proximal and the distal jejunum (located 10 cm and 52 cm caudad to the ligament of Treitz, respectively). With one barostat, standardized distentions (1 minute duration at 10-minute intervals in 4-mm Hg increments) were produced; with the other barostat, intestinal tone was measured as volumetric variations at constant pressure. Perception was scored (0-6) by a questionnaire. The proximal jejunum relaxed in response to distention of the distal jejunum (mean +/- SE, 40% + 7% delta vol; 5.1 + 0.1 perception score at the threshold for discomfort; P less than 0.05 for both). In contrast, the distal jejunum did not respond to distention of the proximal jejunum, whereas the perception scores were similar (10% +/- 5% delta vol; 5.1 +/- 0.1 perception score). Thus, the responsiveness of the proximal jejunum to intestinointestinal reflexes fades distally, whereas intestinal sensitivity to distention remains uniform.

Adult↗

The origin of symptoms on the brain-gut axis in functional dyspepsia.

It was hypothesized that symptoms in functional dyspepsia are originated by an altered mechanism at the brain-gut axis (one or several) in the process of gastric accommodation to a meal. To test the key mechanisms potentially involved in symptomatic gastric accommodation, the sensorial responses (on a 0-10 perception score) and the gastric tone responses (by electronic barostat) to either gastric accommodation (n = 10) or to cold stress (n = 10) were measured in 20 patients with functional dyspepsia and 20 healthy controls. The mechanical accommodation of the stomach to gastric distention (compliance) was similar in patients (52 +/- 8 mL/mm Hg) and controls (57 +/- 6 mL/mm Hg). However, isobaric gastric distention elicited more upper abdominal discomfort in dyspeptics than in controls (perception scores, 4.7 +/- 0.9 vs. 1.1 +/- 0.5, respectively; mean +/- SE; P less than 0.005). Cold stress induced a similar gastric relaxatory response in dyspeptics and controls (delta vol, 145 mL +/- 40 mL vs. 141 mL +/- 42 mL, respectively); hand perception (scores, 8.3 +/- 0.4 vs. 7.9 +/- 0.4, respectively) and autonomic responses were also similar. It is concluded that an abnormal afferent sensorial pathway (altered gastric perception) may be a major mechanism of symptom production in functional dyspepsia.

Adult↗

Reflex changes in intestinal tone: relationship to perception.

Using an original technique, we demonstrated a modulation of intestinal tonic muscular activity (intestinal tone) by intestino-intestinal reflexes. In 11 healthy volunteers we quantitated intestinal tone variations as changes in the air volume within a flaccid bag (12 cm long) located in the proximal jejunum and maintained at a constant pressure by an electronic barostat. Validation studies with glucagon showed significant intestinal relaxation (117 +/- 10% delta vol; P less than 0.05). In six healthy volunteers, graded balloon distensions (1 min duration at 10-min intervals in 8-ml stepwise increments) were randomly performed 8 cm orad, 8 cm caudad, and 20 cm caudad to the bag of the barostat. Perception was scored (0-6) by a questionnaire. Distensions at the three sites induced similar perception; at the threshold for discomfort (score greater than or equal to 5) distension also induced intestinal relaxatory responses (43 +/- 10%, 34 +/- 5%, and 32 +/- 4% delta vol from orad to caudad, respectively; P less than 0.05 for all). However, while unperceived orad distensions (13 +/- 2 ml) induced reflex relaxation (21 +/- 6% delta vol; P less than 0.05), 20-cm-caudad distensions at higher levels (16 +/- 2 ml, 2.7 +/- 0.5 perception score; P less than 0.05) did not (1 +/- 7% delta vol). This dissociation between perception and intestinal tone reflexes suggests that both responses to intestinal distension are mediated by specific mechanisms.

Adult↗

Perception and reflex relaxation of the stomach in response to gut distention.

Acute intestinal distention in dogs induces a gastric relaxatory reflex. Our aim was to investigate this reflex in humans, including its relationship to perception. In 9 fasting healthy volunteers, we performed graded balloon distentions (2.5 min duration at 10-min intervals) of either the antroduodenal junction (n = 6) or the distal duodenum (n = 6). Gastric tone was quantified as changes in the volume of air within an intragastric bag maintained at a constant pressure by an electronic barostat. Perception was scored by a graded (0-6) questionnaire. Distention of the antroduodenal junction induced dose-related gastric relaxatory responses: distention at a level producing significant perception (5.0 +/- 0.1 perception score) induced significant relaxation (203 +/- 39 ml change in intragastric volume; p less than 0.05); lower levels of distention still induced relaxation (113 +/- 30 ml change in volume; p less than 0.05) without significant perception (1.0 +/- 0.5 perception score). In the distal duodenum, distention at the threshold for discomfort (5.1 +/- 0.3 perception score) induced significantly smaller gastric relaxatory responses (42 +/- 17 ml change in volume). Distentions below the level of significant perception (1.5 +/- 0.7 perception score) failed to induce gastric responses (14 +/- 15 ml change in volume). These data indicate that both perceived and unperceived gastric relaxatory reflexes in response to distention exist in humans and that these reflexes are region dependent.

Adult↗

Isobaric intestinal distension in humans: sensorial relay and reflex gastric relaxation.

To determine the relationship between perception of segmental intestinal distension and the reflex gastric tone response, we performed in eight healthy volunteers graded isobaric distensions (2.5 min duration at 10 min intervals) of the duodenum and the jejunum using an electronic barostat. We measured gastric tone as intragastric air volume by a separate barostat and the perception score by a graded questionnaire. At the threshold distending pressure for discomfort in the duodenum (23 +/- 2 mmHg), both perception (5.7 +/- 0.2 score; P less than 0.01) and reflex gastric relaxation (148 +/- 35 ml delta gastric vol; P less than 0.01) were elicited. Lower pressures (12 mmHg below the discomfort threshold) failed to produce perception (0.6 +/- 0.4 score), but significant relaxation was still induced (63 +/- 22 ml delta gastric vol; P less than 0.05). In contrast, no significant gastric relaxation occurred at any pressure level tested in the jejunum (up to 27 +/- 2 mmHg), whereas the perception scores paralleled those produced by duodenal distension. This dissociation between symptoms and visceral reflexes suggests that both responses are independently induced by specific mechanisms.

Adult↗

Cyclic motility in canine colon: responses to feeding and perfusion.

To further characterize colonic motility in the dog and to examine the effects of intraluminal contents, motor activity in conscious animals was recorded by perfused intraluminal catheters. Animals were studied first with the bowel intact and, later, the colon was fashioned into an isolated loop. In the fasting state, cycles of motility recurred approximately each 30 min. These consisted of sequences of phasic contractions (bursts) that migrated variable distances in either direction; stationary bursts were also recorded. The fasting patterns recorded from intact bowel and isolated loops were not different. Feeding increased colonic motility, and the mean periodicity of cyclic bursts was reduced significantly to approximately 20 min. Moreover, differences were observed between intact bowel and isolated loops in the postprandial period. Diversion of chyme from the colon significantly reduced the motor response to food, but only in the late (2-4 hr) postprandial period, when the less frequent, fasting cycle returned to the loops. Perfusion of isolated loops with chyme or saline reestablished the postprandial pattern seen in intact bowel. The results suggest that the volume, but not the composition, of luminal contents modify postprandial motility in the canine colon. Additional experiments confirmed that, in particular, volatile fatty acids were probably not important determinants of colonic motility in the dog.

Animals↗

Relaxatory responses of canine proximal stomach to esophageal and duodenal distension. Importance of vagal pathways.

The viscerovisceral reflex control of gastric tone remains poorly characterized. We have previously demonstrated physiological variations in gastric tone that occur during fasting and after feeding. These variations are neurally regulated. We have now compared the reflex mechanisms modulating gastric tone that are elicited by esophageal or duodenal distension in fasted, conscious dogs. To determine the pathways involved in these reflexes, we combined the technique of vagal blockade (by cooling the supradiaphragmatic vagi isolated within a surgically implanted cooling jacket) with the administration of autonomic drugs. Gastric tone was measured as the air volume within an intragastric bag maintained at a constant, low pressure by an electronic barostat. Standardized distensions were performed by means of an inflatable balloon-catheter positioned either in the mid-esophagus (in three dogs) or in the distal duodenum (in three dogs). A profound and consistent gastric relaxation was induced by distension of either the esophagus (247 +/- 21 ml delta volume, P less than 0.05) or the duodenum (238 +/- 29 ml, P less than 0.05). Supradiaphragmatic vagal cooling abolished the gastric relaxatory response to duodenal distension and significantly reduced, but did not completely suppress, the response to esophageal distension. Neither cholinergic stimulation (intravenous bethanechol) nor adrenergic blockade (combined intravenous phentolamine and propranolol) had any significant effect on either gastric relaxatory response. Combined adrenergic and cholinergic (intravenous atropine) blockade induced gastric relaxation, but failed to suppress the gastric responses. We conclude that both esophageal and duodenal distension elicit gastric relaxation by a noncholinergic vagal mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Meal reduces sensitivity of the stomach to pharmacologically induced dysrhythmia.

The aim of this study was to determine whether food ingestion causes a change in the susceptibility of the stomach to dysrhythmia or in the characteristics of gastric dysrhythmia. The susceptibility of the stomach to develop dysrhythmia was measured by determining the median effective dose of four different drugs known to produce gastric dysrhythmia. These drugs were epinephrine, PGE2, met-enkephalin, and glucagon. The median effective dose for inducing gastric dysrhythmia was measured in four healthy conscious dogs by Dixon's up-and-down method during fasting and after feeding. The median effective dose of epinephrine, PGE2, met-enkephalin, and glucagon were higher after feeding (16.6, 16.6, 35.1, greater than 221 micrograms/kg, respectively) than during fasting (1.7, 5.2, 11.1, 61.0 micrograms/kg, respectively). The results indicate that feeding renders the stomach less susceptible to pharmacologically induced dysrhythmia. However, characteristics of gastric dysrhythmias, such as site of origin and direction of propagation, were similar whether they occurred during fasting or after feeding.

Animals↗

Gastric electromechanical and neurohormonal function in anorexia nervosa.

The gastrointestinal motor function in patients with anorexia nervosa is poorly understood, although it may be relevant to the pathophysiology of the disorder. We have undertaken a multidisciplinary study of 8 patients with anorexia nervosa and 8 age- and sex-matched controls. We have characterized their gastrointestinal and neurohormonal function by measuring (a) gastric electrical activity, (b) antral phasic pressure activity, (c) gastric emptying of solids and liquids, and (d) hormonal and autonomic function. Patients with anorexia nervosa at the time of the initiation of therapy presented with (a) increased episodes of gastric dysrhythmia (mean percentage of dysrhythmic time: 9.75 patients vs. 0.48 controls during fasting, p less than 0.02; 7.21 patients vs. 0.18 controls postcibally, p less than 0.001), (b) impaired antral contractility (mean motility index, 12.8 patients vs. 14.2 controls, p less than 0.002), (c) delayed emptying of solids, (d) decreased postcibal blood levels of norepinephrine and neurotensin (levels of beta-endorphin, insulin, glucagon, gastric inhibitory polypeptide, gastrin, cholecystokinin, and human pancreatic polypeptide were normal), and (e) impaired autonomic function (resting diastolic blood pressure and skin conductance were decreased and the response to the cold pressor test was dampened). Differences between patient and control groups were statistically significant. We conclude that patients with anorexia nervosa present multiple gastrointestinal abnormalities involving control mechanisms as well as target organs.

Adolescent↗