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Biomedical subjects

F Azpiroz

Publications and source records attributed to F Azpiroz.

At least 19 recordsLinked to original sources

Gastric wall tension determines perception of gastric distention.

BACKGROUND & AIMS: The primary mechanism that originates symptoms in response to gastric distention remains undefined. The aim of this study was to determine which factor, whether intragastric volume, pressure, or wall tension, determines perception of gastric distention. METHODS: Healthy subjects underwent increasing gastric distentions (2-minute duration at 5-minute intervals) either at fixed pressure levels using a conventional barostat (n = 10) or at fixed tension levels using a newly developed computerized tensostat (n = 12); perception was scored by a 0-6 scale. Distentions were performed during basal conditions (intravenous saline) and during gastric relaxation by glucagon administration (4.8 microgram/kg intravenous bolus plus 9.6 microgram. kg-1. h-1 infusion). RESULTS: Isobaric distentions with the conventional barostat produced more intense perception during glucagon (95% +/- 40% higher; P < 0.05). However, the factor that determined higher perception could not be ascertained, because at the same pressure levels both intragastric volume and wall tension were greater during glucagon administration (174% +/- 56% and 34% +/- 8% greater, respectively; P < 0.05 vs. saline for both). The tensostat evidenced that perception was selectively related to tension, not to elongation; during glucagon administration, intragastric volumes were significantly larger (80% +/- 28% larger increase; P < 0.05), but perception of isotonic distentions remained the same (27% +/- 22%; nonsignificant change). CONCLUSIONS: Gastric wall tension, but not intragastric volume, determines perception of gastric distention, at least below nociception.

Adult↗

Principles of applied neurogastroenterology: physiology/motility-sensation.

Many of the symptoms characteristic of the functional gastrointestinal disorders (FGID) are consistent with dysfunction of the motor and/or sensory apparatus of the digestive tract. Those aspects of sensorimotor dysfunction most relevant to the FGID include alterations in: gut contractile activity; myoelectrical activity; tone and compliance; and transit, as well as an enhanced sensitivity to distension, in each region of the gastrointestinal tract. Assessment of these phenomena involves a number of techniques, some well established and others requiring further validation. Using such techniques, researchers have reported a wide range of alterations in sensory and in motor function in the FGID. Importantly, however, relationships between such dysfunction and symptoms have been relatively weak, and so the clinical relevance of the former remains unclear. Moreover, the proportions of patients in the various symptom subgroups who display dysfunction, and the extent and severity of their symptoms, require better characterization. On a positive note, progress is occurring on several fronts, especially in relation to functional dyspepsia and irritable bowel syndrome, and based on the data gathered to date, a number of areas where further advances are required can be highlighted.

Colonic Diseases, Functional↗

Dimensions of gut dysfunction in irritable bowel syndrome: altered sensory function.

Growing evidence suggests that symptoms in patients with irritable bowel syndrome (IBS) may be due to a visceral sensory dysfunction. Specifically, it has been shown that patients with IBS have hypersensitive responses to distension of the rectum, whereas their tolerance to somatic stimuli is normal or even increased. Furthermore, patients with IBS have hypersensitivity of the small bowel, which selectively affects mechanosensitive afferents, with normal perception of electrical stimulation of the gut. Sensory dysfunctions may also be associated with altered reflex activity, which may contribute to the clinical symptoms. Normally, a series of mechanisms at different strata of the nervous system modulate visceral afferent input and determine conscious perception. Conceivably, a dysfunction of these regulatory mechanisms may alter sensitivity in clinical conditions. To date, neither the origin nor the clinical significance of visceral hyperalgesia has been elucidated. However, it seems likely that the sensory and reflex dysfunctions of the gut in IBS may combine to different degrees, and their interaction may explain the clinical pleomorphism of the syndrome.

Colonic Diseases, Functional↗

Modulation of gut perception in humans by spatial summation phenomena.

1. We have recently shown that perception of intestinal stimuli increases by spatial summation phenomena. Our aim was to determine in humans whether intestinal perception depends on (a) the length of gut stimulated, and (b) the distance between stimuli. 2. In a first series of studies, we compared perception of isobaric intestinal distensions applied over a 3 cm segment and a 36 cm segment by means of two separate barostats (n = 8). In a second series of studies we compared perception of intestinal distensions applied simultaneously by two balloons sited 3, 12 or 48 cm apart (n = 6). 3. Distension of the 36 cm segment induced significantly greater perception than distension of the 3 cm intestinal segment (discomfort perceived at 20 +/- 2 mmHg and 31 +/- 2 mmHg, respectively; P < 0.05). Perception of intestinal balloon distension increased when a second stimulus was simultaneously applied, independently of the distance between the two balloons (the discomfort thresholds were 30 +/- 11, 20 +/- 6 and 28 +/- 7% lower with simultaneous distensions 3, 12 and 48 cm apart, respectively). 4. We conclude that perception of intestinal distension is determined by the extension of the field of stimulation, and the summation effect is similar whether adjacent or distant fields are stimulated.

Adult↗

Intestinal gas dynamics and tolerance in humans.

BACKGROUND & AIMS: Abdominal symptoms are often attributed to intestinal gas. In humans, gas production and composition have been previously investigated, but intestinal gas dynamics and tolerance remain virtually unknown. The aim of this study was to establish the relationship between intestinal gas loads, evacuation, perception of symptoms, and objective abdominal distention in healthy humans. METHODS: A dose-response study was performed in 46 healthy subjects; intestinal gas was infused for 3 hours (0, 1, 4, 12, and 30 mL/min), and anal gas evacuation, symptom perception, and abdominal distention were measured. A mixture of gases was infused in venous proportions to minimize diffusion. Anal gas recovery and calculations of gas retention were validated using sulfur hexafluoride as a nonabsorbable gaseous marker. RESULTS: At all of the infusion rates, gas evacuation rapidly equilibrated and paralleled gas infusion without significant differences in perception. Only 6 subjects retained >400 mL gas, and 5 of them developed abdominal distention and symptoms. By contrast, all but 4 of the 41 subjects without retention tolerated the gas loads without discomfort. CONCLUSIONS: Intestinal gas tolerance is normally high, because expeditious gas transit and evacuation prevent gas pooling and symptoms. When this protective mechanism is insufficient, gas retention occurs, and it causes abdominal symptoms and distention.

Abdomen↗

Endogenous cholecystokinin enhances postprandial gastroesophageal reflux in humans through extrasphincteric receptors.

BACKGROUND & AIMS: Exogenous cholecystokinin (CCK) decreases lower esophageal sphincter (LES) pressure and increases transient LES relaxations (TLESRs) in humans. The aims of this study were to determine whether endogenous CCK increases gastroesophageal reflux in humans and whether this is a direct effect on the LES. METHODS: Esophageal pH, LES pressure, and gallbladder volume were measured in 8 healthy volunteers after ingestion of a 181-kcal meal alone or adding 12 g cholestyramine to increase endogenous CCK release. In 7 additional volunteers, the effect of cholestyramine was studied during intravenous perfusion of saline or the CCK-A receptor antagonist loxiglumide. In circular LES strips from 9 transplant donors, we measured the effect of CCK-8 (10(-11) to 3 x 10(-8) mol/L) on basal tension and on electrical field-induced relaxation. RESULTS: Cholestyramine increased gallbladder emptying, reflux episodes, TLESRs, and time of esophageal pH of <4. Loxiglumide inhibited postprandial gallbladder emptying, reflux episodes, TLESRs, and time of pH of <4 and prevented the decrease in LES pressure induced by cholestyramine. In vitro, CCK-8 contracted LES strips through a tetrodotoxin-insensitive pathway but did not modify electrical field-induced LES relaxations. CONCLUSIONS: Endogenous CCK enhances postprandial gastroesophageal reflux in humans by increasing the rate of TLESRs and reduces postprandial LES pressure. These actions seem mediated by extrasphincteric CCK-A receptors that override a direct contractile effect of CCK on the LES muscle.

Adult↗

Gastric neurology: evolving concepts and techniques.

Gastric function is finely modulated by a series of neurological mechanisms, so that gastric digestion is normally not perceived. Alteration of these control mechanisms may lead to different situations, which are frequently associated with symptoms. An impaired tonic contraction of the proximal stomach, that is, an impaired gastric tone, results in gastroparesis. Patients with functional dyspepsia, and also patients with achalasia, have impaired meal accommodation of the stomach. Interestingly, patients with functional dyspepsia may also have a sensory dysfunction, and both dysfunctions could play a synergistic role. However, the sensory dysfunction in dyspepsia, particularly the types of afferent fibres affected, and the mechanisms of impaired accommodation, still remain to be characterized. Evaluation of gastric function has been approached using the barostat. However, the barostat has limitations and potential technical pitfalls that require proper attention. Meal ingestion induces a variety of reflexes and the net result is a relaxation of the stomach. However, gastric reflexes can be best evaluated with the stomach empty, when the stimuli are applied at a different site. Nevertheless, altered reflex responses may be difficult to interpret. For instance, absent or decreased relaxatory responses may equally correspond to a gastroparetic stomach without tone or to a dyspeptic stomach unable to relax. In this context, it may be important to measure basal tone. Distension of the stomach by means of the barostat has been also used to test gastric sensitivity. However, recent studies have shown that perception of gastric distension relays on stimulation of tension receptors; since wall tension depends on both pressure and volume, distension with the barostat may be difficult to standardize. Hopefully, a battery of tests may become available in the near future for a complete neuromuscular evaluation of the gut.

Gastrointestinal Motility↗

Perception and gut reflexes induced by stimulation of gastrointestinal thermoreceptors in humans.

1. Experimental studies in animals suggest the existence of thermoreceptors in the gastrointestinal tract. Our aim was to investigate the distribution and specificity of upper gut thermoreceptors in humans. 2. In healthy subjects, thermal stimulation of the stomach (n = 8) and the small intestine (n = 6) was produced by means of a thermostat, which recirculates water at adjusted temperatures through an ultrathin intraluminal bag. Progressively warm (42, 47 and 52 degrees C) and cold (32, 22 and 12 degrees C) stimuli of 3 min duration were alternately applied at 13 min intervals. Perception was scored on a scale of 0-6 and gastric tone responses were measured with a barostat. 3. Thermal stimuli induced specific responses: cold stimuli induced abdominal cold sensation and a reflex contraction of the stomach, whereas warm stimuli induced warm sensation and a reflex gastric relaxation. 4. Thermal stimuli induced similar stimulus-related perception in the stomach and small intestine (temperatures between 12 and 49.5 +/- 0.5 degrees C were tolerated). 5. The reflex responses were site specific. Warm and cold stimulation of the stomach induced gastric reflexes (76 +/- 26 ml isobaric expansion at 47 degrees C, and 68 +/- 10 ml contraction at 12 degrees C; P < 0.05 for both). However, only warm, not cold, stimulation of the intestine induced enterogastric reflexes. 6. These results indicate that in humans, warm and cold receptors are distributed along the gastrointestinal tract and project afferent input both into perception and reflex circuits with specific topographic organization.

Adult↗

Attention and distraction: effects on gut perception.

BACKGROUND & AIMS: Paying attention to the gut may magnify perception of abdominal symptoms, but the actual influence of attention by anticipatory knowledge and distraction on gut perception remains poorly defined. The aim of this study was to determine whether mental activity, attention vs. distraction, affects intestinal perception and whether mental effects are synergistic with other modulatory mechanisms. METHODS: Perception of 1-minute intestinal balloon distentions applied at 7-13-minute random intervals was measured in healthy subjects. First, distentions were tested during attention by anticipatory knowledge and during distraction (n = 8). Because somatic transcutaneous electrical nerve stimulation (TENS) reduces gut perception, distentions were then tested during attention alone, attention plus somatic TENS, and during distraction plus TENS (n = 8). RESULTS: Perception of intestinal distentions was higher during attention than during distraction (3.3 +/- 0.2 vs. 2.9 +/- 0.1 [mean +/- SEM]; P < 0.05). The area of somatic projection was greater during attention (P < 0.05). Intestinal compliance and oral reflex relaxation remained unchanged. During application of somatic TENS, perception of intestinal distention was higher during attention than distraction (2.4 +/- 0.3 vs. 1.7 +/- 0.2; P < 0.05). However, TENS did not alter the perception score during attention. CONCLUSIONS: Mental activity may modulate gut perception and overrides the effects of somatic TENS on gut perception.

Adult↗

Gastrogastric reflexes regulating gastric tone and their relationship to perception.

Our aim was to investigate in humans the gastrogastric reflexes that regulate gastric tone and their relationship to perception. In nine healthy subjects, liquid distension (in 100-ml steps), warm stimuli (in 3 degrees C increments), and cold stimuli (in 6 degrees C decrements) were randomly applied in the stomach for 3 min at 8-min intervals. Gastric tone was measured as isobaric volume changes of air by a barostat, and perception was scored by a graded (0-6) questionnaire. Liquid accommodation produced an additional expansion of isobaric air maintained by the barostat (51 +/- 13 ml with 100 ml of liquid filling, P < 0.05), but this effect became inconsistent with further filling. An accommodation-like reflex was best evidenced by warm stimulation below the discomfort threshold (58 +/- 13 ml relaxation at 47 +/- 1 degrees C, P < 0.05). By contrast, cooling below discomfort induced a reflex contraction (-62 +/- 22 ml change at 18 +/- 2 degrees C, P < 0.05). In conclusion, gastric tone, i.e., accommodation and contraction, is modulated by a net of reflexes that arise from the proper wall of the stomach below the discomfort threshold.

Adult↗

Bowel habit after cholecystectomy: physiological changes and clinical implications.

BACKGROUND & AIMS: Scarce data suggest that cholecystectomy may alter bowel habit. The aim of this study was to determine whether cholecystectomy modifies gut transit. METHODS: Five experimental groups were studied: 29 patients with uncomplicated gallstones before and 1 month after elective cholecystectomy, 22 patients 4 years after elective cholecystectomy, 14 patients with postcholecystectomy diarrhea, 5 patients with acute infectious diarrhea (disease controls), and 13 patients before and 1 month after other elective surgery (surgical controls). All participants underwent measurement of colonic transit by a modified radiopaque pellet method and orocecal transit by the standard lactulose breath H2 test. RESULTS: One month postoperatively, cholecystectomy had substantially accelerated total colonic transit (51 +/- 5 hours before vs. 38 +/- 5 hours after; P < 0.05) and delayed slightly orocecal transit (80 +/- 4 minutes before vs. 103 +/- 8 minutes after; P = 0.05). Similar colonic and orocecal transit times were measured 4 years after cholecystectomy (40 +/- 4 hours and 105 +/- 8 minutes, respectively). Colonic transit times in patients with the postcholecystectomy diarrhea syndrome were accelerated as much as in patients with infectious diarrhea, who served as controls (19 +/- 3 hours and 15 +/- 4 hours, respectively). Surgery per se had no effect on gut transit. CONCLUSIONS: Cholecystectomy shortens gut transit by accelerating colonic passage. These sequelae develop early and persist at least 4 years after cholecystectomy. The postcholecystectomy diarrhea syndrome probably represents a magnification of the above colonic sequelae.

Adult↗

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-micrograms/kg bolus plus 9.6 micrograms.kg-1.h-1 infusion). RESULTS: The same distending pressure 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.

Adult↗

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↗