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Biomedical subjects

F Azpiroz

Publications and source records attributed to F Azpiroz.

At least 55 records · Page 3Linked to original sources

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↗

Antroduodenal resistance to flow in the control of duodenogastric bile reflux during fasting.

Our objectives in this study were (a) to determine the role of antroduodenal resistance in the control of fasting duodenogastric bile reflux in the dog and (b) to elucidate the contribution of the pylorus both to resistance and to reflux. Thus, we measured simultaneously throughout the interdigestive motor cycle (a) antroduodenal pressure activity by manometry, (b) antroduodenal resistance by a pneumatic resistometer, and (c) bile acid concentrations in duodenal and gastric juices. Experiments were performed in 15 conscious dogs (9 with pylorus intact and 6 with extramucosal pyloric myotomy). We found that antroduodenal resistance was lowest during phase I, increased gradually during phase II, and peaked during phase III (linear trend, p less than 0.001). Duodenogastric bile reflux was low during phase I, peaked during late phase II, and decreased again during phase III (quadratic trend, p less than 0.05). Therefore, variations in net resistance and reflux were differently related to the phases of the interdigestive motor complex. Pyloric myotomy significantly decreased antroduodenal resistance (linear trend different from control, p less than 0.001), but had no significant effect on duodenogastric bile reflux. We conclude (a) that changes in net antroduodenal resistance do not regulate duodenogastric bile reflux and (b) that the pylorus is an important determinant of antroduodenal resistance, but has no major role in the control of fasting duodenogastric bile reflux.

Animals↗

Gastric tone measured by an electronic barostat in health and postsurgical gastroparesis.

Using a gastric barostat we have studied interdigestive variations in gastric tone and its response to gastric distention in 17 healthy volunteers and 5 patients with postsurgical gastroparesis. The barostat measures tone by monitoring the volume of air within a flaccid intragastric bag, maintained at a constant, preselected pressure level by an electronic feedback mechanism. In healthy individuals, inter-digestive variations in gastric tone were phase-locked in advance of duodenal interdigestive motor activity and consisted of three sequential periods; a quiescence period, an intermediate period, and a period of activity. In contrast to controls, gastroparetic patients presented significantly larger intragastric volume at low intragastric pressure (6 mmHg). Gastric distention (14 mmHg) resulted in significantly reduced extension ratio and phasic motor response in the gastric remnant. Furthermore, distention elicited a symptomatic response that resembled their postcibal syndrome (epigastric fullness, pain, nausea). These data suggest that postsurgical gastroparesis is associated with impaired tone of the residual gastric pouch.

Adult↗

Importance of vagal input in maintaining gastric tone in the dog.

1. Using a gastric barostat to quantify variations in gastric tone, we had previously demonstrated that food ingestion or intestinal nutrient perfusion induces gastric relaxation. These data suggested a basal tonic contraction of the stomach during fasting. 2. To determine the role of vagal input in maintaining fasting gastric tone, we prepared two chronic canine models, either isolating both cervical vagal trunks in a cutaneous tunnel or including the supradiaphragmatic vagi within an implanted cooling jacket. In the fasted conscious dogs, we then studied the effect, on gastric tone, of acute and reversible vagal blockade by cooling. 3. Cervical vagal cooling produced a reversible gastric relaxation and increased the heart rate. Supradiaphragmatic vagal cooling produced a similar gastric relaxation without the cardiac effect. 4. Adrenergic blockade did not change either the base-line gastric tone or the cooling-induced relaxation. Adrenaline decreased gastric tone, but vagal cooling still produced a significant relaxation. 5. Atropine alone or combined with adrenergic antagonists produced a gastric relaxation that was not further increased by vagal cooling. Bethanechol increased gastric tone, an effect unchanged by vagal cooling. 6. We conclude that gastric tone during fasting is maintained by a cholinergic input, which is vagally mediated at both the cervical and the supradiaphragmatic levels.

Animals↗

Reflex gastric relaxation in response to distention of the duodenum.

Using a newly developed gastric barostat, we studied the effect of duodenal distention on gastric tone in a chronic canine model. In the conscious, fasted dogs, duodenal distention for 15 s consistently induced a marked gastric relaxation (delta intragastric volume = 226 +/- 23 ml). This response could be induced repeatedly without evidence of fatigue. Neither bethanechol nor combined phentolamine and propranolol infused intravenously had any significant effect on gastric relaxation in response to duodenal distention. To investigate the pathway of this duodenogastric mechanism, in four dogs we isolated the vagal nerves at the supradiaphragmatic level within an implanted cooling jacket. During intravenous infusion of bethanechol (used as a cholinergic background to maintain base-line gastric tone), supradiaphragmatic vagal blockade by cooling abolished the gastric relaxatory response to duodenal distention (delta intragastric volume = 11 +/- 5 ml during vagal blockade vs. 194 +/- 36 after vagal rewarming; P less than 0.05). This effect of acute and reversible vagal blockade by cooling was also mimicked by bilateral surgical vagotomy. We conclude that a nonadrenergic, noncholinergic mechanism participates in gastric relaxation induced by duodenal distention. This mechanism is mediated by the vagus nerve.

Animals↗

Pyloric contribution to antroduodenal resistance to flow in the conscious dog.

We have developed a pneumatic resistometer to monitor antroduodenal resistance to flow for prolonged periods of time in conscious dogs. To investigate the specific contribution of the pylorus to antroduodenal resistance we compared resistance during fasting in four control dogs and in four dogs with extramucosal pyloric myotomy (1.5 cm long). After pyloric myotomy, as in controls, resistance to flow changed cyclically, being lowest during phase I and highest during phase III of the interdigestive motor cycle. Pyloric myotomy decreased resistance during phase III. Atropine (0.1 mg X kg-1 X h-1) administered during motor quiescence (phase I) reduced resistance in the control group (P less than 0.05) but not in myotomized animals. Bethanechol (0.2 mg X kg-1 X h-1) significantly increased resistance in both groups (P less than 0.05). We conclude that antroduodenal resistance to flow is related to cyclic interdigestive motility. The pylorus is the predominant determinant of antroduodenal resistance during motor quiescence, but its contribution diminishes markedly during motor activity.

Animals↗

Characteristics of spontaneous and drug-induced gastric dysrhythmias in a chronic canine model.

We developed a chronic canine model to study electrical characteristics of both spontaneously occurring and drug-induced gastric dysrhythmias. Seven female dogs were fitted with a catheter chronically implanted in the left gastric artery, and five monopolar silver-silver chloride electrodes were sutured to the serosa of the stomach and proximal duodenum. Three dogs exhibited spontaneous dysrhythmia, and in 4 other dogs, dysrhythmias were drug-induced. Ninety-seven episodes of spontaneous dysrhythmia and 21 episodes of drug-induced dysrhythmia were recorded and analyzed. All episodes of tachygastria were first detected in the distal antrum, and the tachygastric pacesetter potentials usually spread orally. All but one episode of bradygastria were detected both in the corpus and the antrum simultaneously. During bradygastria, pacesetter potentials spread aborally. Spontaneous and drug-induced dysrhythmias exhibited similar characteristics. Therefore, we conclude that the origin and propagation characteristics of gastric dysrhythmias depend on the type of dysrhythmia rather than whether they are spontaneous or drug-induced.

Animals↗

Scintigraphic measurements of canine ileocolonic transit. Direct and indirect effects of eating.

Eight dogs were equipped with ileal catheters, 50 cm proximal to the ileocolonic junction, and serosal electrodes at 5, 25, 55, 100, and 150 cm. Transit was assessed by injecting a bolus of 99mTc-diethylenetriamine pentaacetic acid through the ileal catheter and following isotope movements by serial, 4-min scintiscans. Isotope was injected in separate studies: during phase I of an interdigestive myoelectrical cycle, 10 min before a meal, and or 2 or 4 h after a meal (600 ml, 385 kcal, thickened with 4 g guar). At another time, mouth-to-colon transit of the same meal was measured by labeling it with 111In-diethylenetriamine pentaacetic acid and scanning at hourly intervals for 11 h. Transit of isotope through the terminal ileum and entry into the colon was characteristically erratic; long periods of immobility were interspersed with sudden "bolus" movements. In the fasting studies, most sudden movements occurred while phase III (migrating motor complex) of the interdigestive myoelectrical cycle migrated through the last 50 cm of ileum. Passage of a single migrating motor complex through the terminal ileum propelled about one-half the dose of isotope into the colon; complete clearance of the ileum required two or more migrating motor complexes. Immediately after the meal, ileal movements increased transiently; however, these were followed by a period of quiescence. Overall, the time for 50% of the counts to enter the colon was not different when isotope was injected 10 min before the meal from when the injection was made 2 h postprandially (207 +/- 16 min and 162 +/- 25 min, respectively). However, transit of isotope injected 4 h postprandially was significantly faster (91 +/- 13 min). In the fed state, some bolus movements could be related to specific patterns of ileal motility; however, the majority occurred during apparently random "fed-type" motility. In part II, meal marker accumulated faster in the colon after 3-4 h, suggesting that the rapid ileocecal transit at 4 h postcibal was due to increased flow of chyme through the ileum at this time.

Animals↗

Measurement of resistance to flow across antroduodenal area during fasting.

Changes in antroduodenal resistance to flow may participate in the regulation of gastric emptying and duodenogastric reflux. Little is known, however, about the relationship between antroduodenal resistance and the physiological patterns of contractile activity in this area. We have developed an instrument that maintains an electronically regulated constant-pressure gradient of 2 mmHg across both ends of a flaccid cylinder positioned fluoroscopically across the pylorus. Because resistance bears a constant inverse relationship to flow at a fixed pressure gradient, changes in the recorded rate of airflow through the cylinder are a measure of antroduodenal resistance. In vitro studies showed that, under these conditions, airflow was a function of the diameter and length of the air path and the frequency and duration of external pressure waves greater than 2 mmHg. In vivo studies in four dogs examined the relationship between interdigestive phases of motor activity and variations in resistance exerted by the antroduodenal area. We found that flow rates varied markedly with each phase. Antroduodenal resistance was lowest during motor quiescence (phase I), rose gradually during irregular activity (phase II), and reached its peak during maximal contractile activity (phase III) (P less than 0.05). Resistance was similar for antegrade and retrograde flow. Additional studies suggested that the pyloric area contributes mostly to resistance during phase I, whereas duodenal resistance at least matches that of the pylorus during phase III.

Air↗

Vagally mediated gastric relaxation induced by intestinal nutrients in the dog.

Using a gastric barostat to measure gastric tone, we previously demonstrated that nutrient perfusion into the intestine induces gastric relaxation. To investigate the pathway of this enterogastric reflex we surgically isolated the vagi either in a cervical skin tunnel (3 dogs) or within an implanted supradiaphragmatic cooling jacket (3 dogs). In the conscious fasted dogs, cervical or supradiaphragmatic vagal blockade by cooling (5 degrees C X 10 min) induced a reversible gastric relaxation. Bethanechol (0.2 mg X kg-1 X h-1 iv) alone or in combination with adrenergic blockers (phentolamine 1.5 mg X kg-1 X h-1 + propranolol 0.3 mg X kg-1 X h-1) suppressed the cooling-induced relaxation but did not abolish gastric relaxation induced by intestinal nutrient perfusion (Osmolite, 3.1 ml/min). At this point, vagal cooling, either cervical or supradiaphragmatic, reversibly blocked the nutrient-induced gastric relaxation: gastric tone significantly increased driven by the cholinergic background and reverted after vagal rewarming to the previous relaxed state. We conclude that intestinal nutrients induce gastric relaxation by a nonadrenergic noncholinergic mechanism. This reflex is mediated by fibers contained in the vagus nerves at both cervical and supradiaphragmatic levels.

Animals↗

Physiological variations in canine gastric tone measured by an electronic barostat.

Gastric tone may mediate gastric accommodation and emptying; however, it cannot be recorded by manometric methods. We have developed an electronic barostat that maintains a constant pressure (2 mmHg) within an air-filled bag and have validated the system in vitro and in vivo. In four conscious dogs, the bag was introduced orally into the stomach, and gastric tone was monitored from the barostat as variations in intrabag volume. Simultaneously, we recorded upper gut pressure activity by implanting manometric catheters. Studies were performed in fasting and fed (200-ml solid meal) dogs. The barostat system did not distort fasting motor activity. Intrabag volume correlated with manometrically measured fundic pressure activity. However, tonic changes undetected manometrically were clearly registered by the barostat. Meal induced marked changes in gastric tone. A receptive relaxation during feeding was followed by a low-tone accommodation period. Later, the barostat registered a sustained high tone until the return of the fasting pattern. We conclude that the electronic barostat measures physiological variations in gastric tone that are not recorded by conventional systems.

Animals↗

Contractile patterns and transit of fluid in canine terminal ileum.

Earlier recordings of intraluminal pressure from the terminal ileum and across the ileocolonic sphincter of dogs revealed, in addition to the usual interdigestive and digestive patterns, pressure waves that appeared to have propulsive potential. One of these, which we designated as a "prolonged propagated contraction" (PPC), was a wave of high amplitude; it had a duration much longer than the ileal slow wave and migrated rapidly through the ileum, often into the proximal colon. The other pattern was one of "discrete clustered contractions" (DCC); these were propagated bursts of rhythmic phasic waves, distinct from phase III of the interdigestive myoelectric complex. These migrated through the ileum more rapidly than did phase III. Our aims were to record the electrical and mechanical equivalents of these pressure events using only extraluminal sensors and to evaluate the capacity of these contractions to propel fluids. PPCs and DCCs were recorded by extraluminal strain gauges, and flow was assessed by recovery of a nonabsorbable marker. Phase III of the migrating motor complex propelled fluid through the ileum, but in addition DCCs and, especially, PPCs were able to empty the ileum. These latter contractions have similarities to the ileal "peristaltic rush" described by others, and we believe these waves are an important force for ileal emptying.

Animals↗

Intestinal control of gastric tone.

By use of a newly developed electronic barostat, we investigated chyme-mediated intestinal regulation of gastric tone in a canine model. In this model the proximal (3 dogs) or distal (3 dogs) small intestine was luminally isolated, maintaining neuromuscular continuity. Gastric tone was measured by recording variations in the volume of air within an intragastric bag that was maintained at a constant pressure (2 mmHg) by the electronic barostat. The isolated intestinal loop was perfused constantly (5 ml/min) with either isotonic saline (control) or with test infusates (osmolality, 300 mosmol/kg; pH 7.4) of carbohydrate (maltose), protein (casein hydrolysate), fat (sodium oleate), or a combination of all three nutrients. The combined nutrient solution, infused into either the proximal or the distal intestine, profoundly inhibited gastric tone. Fat infused into the proximal intestine induced gastric relaxation, whereas protein had only a modest effect and carbohydrate had no effect. In contrast, in the distal intestine carbohydrate and protein markedly reduced gastric tone, whereas fat had no effect. We conclude that nutrients in the small bowel regulate gastric tone by a mechanism that is nutrient and region specific.

Absorption↗

Pressure activity patterns in the canine proximal stomach: response to distension.

The stomach accommodates to distension with a minimal rise in intragastric pressure, but the effects of gastric accommodation on overall gut motor activity are unknown. In four conscious fasted dogs, constant gastric distension (0, 10, 20, 40, 80, 160, 320, and 640 ml) was produced by an air-filled intragastric bag; intrabag and gastrointestinal pressure activities (fundus, antrum, and proximal intestine) were recorded for 4 h. With the bag empty (or without bag), the proximal stomach exhibited a fasting cyclic motor pattern synchronized with that in the antrum and upper intestine. During periods of activity the fundus generated powerful phasic pressure waves. Increasing intrabag volumes up to 80 ml gradually lengthened phase II of the intestinal interdigestive motor cycle. At 160 ml or more, gut cyclic motor activity disappeared and was replaced by continuous irregular activity, although the intrabag pressure increased to less than 7 mmHg. We concluded that gastric distension markedly alters gut motor activity even though gastric accommodation prevents a major increase in intragastric pressure.

Animals↗

Anal sphincteric pressure in fissure-in-ano before and after lateral internal sphincterotomy.

Resting anal canal pressure was measured in 15 patients with anal fissure before and after lateral internal sphincterotomy. This pressure was found to be significantly higher in these subjects (mean 95 +/- 23.08 mm HG) than in the control group (mean 66.10 +/- 14.28 mm Hg) before surgery (P less than 0.005). After surgery, a normal anal canal pressure was produced. The authors maintain that anal canal spasm is responsible for chronicity of anal fissures.

Adolescent↗

Functional dyspepsia: recent pathophysiological advances.

Functional dyspepsia is a clinical syndrome defined by upper abdominal symptoms, without identifiable cause by conventional diagnostic evaluation. New diagnostic tests, such as gastrointestinal manometry and gastric emptying, may help in a better characterization of these patients by demonstrating specific motor abnormalities, such as postprandial antral hypomotility and delayed gastric emptying of solids, or less frequently, intestinal dysmotility patterns indicating a visceral neuropathy. Nevertheless, a substantial proportion of dyspeptic patients have normal motility patterns. Interestingly, recent studies have shown that a gastric hypersensitivity to distension may be the cause of the postprandial symptoms in functional dyspepsia. These data indicate that functional dyspepsia may include an heterogeneous group of patients with different underlying disturbances.

Dyspepsia↗