Distension In Humans Research Articles

Differential symptomatic and electrogastrographic effects of distal and proximal human gastric distension.

Nausea and gastric dysrhythmias occur in conditions associated with gastric distension. The roles of distal and proximal gastric mechanoreceptors in these responses are unexplored. Because antral distension induces vomiting in animals and antral and fundic vagal afferent discharges differ, we hypothesized that distal gastric distension in humans leads to greater symptomatic and dysrhythmic responses than proximal distension. Symptoms and electrogastrograms were recorded in healthy humans during distal and proximal gastric distension with a barostat. Distal but not proximal distension induced nausea and a 747 +/- 250% increase in dysrhythmic power (P < 0.05), responses not affected by granisetron, indomethacin, or atropine, agents that block dysrhythmias in other settings. In the distal stomach, bloating and pain developed at lower pressures (P < 0.05) not modified by granisetron, and compliance was significantly lower (P < 0.05). In conclusion, gastric mechanoreceptor activation in the less-compliant distal stomach produces nausea and dysrhythmias via non-5-hydroxytryptamine3 (5-HT3), non-prostaglandin-dependent, and noncholinergic pathways. Distal mechanoreceptor activation induces greater bloating and pain than proximal mechanoreceptor activation via 5-HT3-independent pathways.

Atrial distension in humans during microgravity induced by parabolic flights

The hypothesis was tested that human cardiac filling pressures increase and the left atrium is distended during 20-s periods of microgravity (microG) created by parabolic flights, compared with values of the 1-G supine position. Left atrial diameter (n = 8, echocardiography) increased significantly during microG from 26.8 +/- 1.2 to 30.4 +/- 0.7 mm (P < 0.05). Simultaneously, central venous pressure (CVP; n = 6, transducer-tipped catheter) decreased from 5.8 +/- 1.5 to 4.5 +/- 1.1 mmHg (P < 0.05), and esophageal pressure (EP; n = 6) decreased from 1.5 +/- 1.6 to -4.1 +/- 1.7 mmHg (P < 0.05). Thus transmural CVP (TCVP = CVP - EP; n = 4) increased during microG from 6.1 +/- 3. 2 to 10.4 +/- 2.7 mmHg (P < 0.05). It is concluded that short periods of microG during parabolic flights induce an increase in TCVP and left atrial diameter in humans, compared with the results obtained in the 1-G horizontal supine position, despite a decrease in CVP.

Determinants of lower esophageal sphincter relaxation induced by esophageal balloon distension in humans

The determinants of the lower esophageal sphincter relaxation response to esophageal distension have not previously been systematically examined in humans. In this study, 14 healthy subjects were tested using a manometry catheter with a sleeve device and three balloons spaced 5 cm apart. Subjects had up to five distensions with each balloon at four different diameters and two different durations of inflation. The results indicated that 1,170 separate distensions were available for analysis. Sphincter relaxation occurred more frequently (P < 0.005) with larger balloon diameters, yet occurred in only 84% of inflations at the largest diameter. Sphincter relaxation was more often observed with the proximal balloon (P < 0.005) during longer distensions (P < 0.05) and when esophageal contractions occurred above the balloon (P < 0.005). Once sphincter relaxation occurred, its magnitude was essentially independent of balloon site and diameter, distension duration, and the presence of proximal contractions. In conclusion, even large balloon distensions do not uniformly produce or maintain lower esophageal sphincter relaxation. Sphincter relaxation is more likely with proximal esophageal distension. The association of sphincter relaxation with vagally mediated proximal contractions suggests vagal modulation of this response.

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.

Perception of intestinal distension in humans as a functional of the extension of gut stimulated: [formula omitted], F. Azpiroz, J-R. Malagelada. Digestive System Research Unit, Hospital General Vall d'Hebron, Barcelona, Spain

Perception of intestinal distension in humans as a functional of the extension of gut stimulated: [formula omitted], F. Azpiroz, J-R. Malagelada. Digestive System Research Unit, Hospital General Vall d'Hebron, Barcelona, Spain

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.

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 μs). 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.

Inhibition of a somatic nociceptive reflex by gastric distention in humans

Background/Aims: The spinal nociceptive RIII reflex, an exteroceptive cutaneous-muscular flexion reflex, is powerfully and specifically inhibited by painful heterotopic somatic stimuli. The aim of the present study was to evaluate the effects of nonpainful and painful visceral stimuli on this reflex.Methods: In nine healthy volunteers, the effects of five levels of gastric distention were tested on the RIII reflex, recorded from the biceps femoris, and elicited by electrical stimulation of the ipsilateral sural nerve. Distentions were performed by means of a balloon that was placed in the proximal part of the stomach and connected to an electronic barostat. The sensations evoked by gastric distention were scored using a graded (0–6) questionnaire. Results: The 200- and 400-mL distention levels elicited no significant modifications of the RIII reflex; the 600-, 800-, and 1000-mL levels inhibited the RIII reflex by 25%, 35%, and 55%, respectively. The magnitude of this inhibition correlated significantly (P < 0.0001) with both the level of distention and the intensity of visceral perception. Conclusions: Gastric distention produces volume-dependent inhibition of the somatic RIII reflex in humans. This model may provide an interesting tool for objective and quantitative evaluation of normal and disturbed visceral sensations in humans.

Multichannel recording of cerebral potentials evoked by esophageal balloon distension in humans.

In order to obtain insight in the generator localization of esophageal evoked potentials, cerebral responses were recorded from 32 scalp electrodes in five healthy volunteers (two male; three female; age 20-30 years), using series of 50 balloon inflations with 15 ml of air. Sequential topographical mapping of waveforms was performed in each subject. Biphasic waveforms were recorded. At Fpz, a positive deflection at 300 and a negative deflection at 465 msec (P300 and N465) were recorded and at Pz, N300 and P465. At Cz the first peak (N270) was slightly earlier than 300 msec. Waveforms were left to right symmetrical. At distal electrodes, biphasic waveforms were recorded (P300 and N465). In four subjects, a gradual phase shift occurred in between the waveforms at midline electrode Cz and the left and right mastoids. Brain mapping showed phase reversals between central negativity and surrounding positivity at about 300 msec, and between central positivity and surrounding negativity at 400-500 msec. Our data suggest the presence of more than one generator in the anterior and dorsal part of the insula and/or dorsal periinsular cortex.

Influence of age on cerebral potentials evoked by oesophageal balloon distension in humans.

The recording of viscerosensory cerebral evoked potentials is a new field in the research on gastrointestinal perception. The aim of our study was to assess the relationships between age and peak amplitudes and latencies of cerebral potentials evoked by balloon distension of the human oesophagus. In 16 healthy volunteers (aged 21-59 years), cerebral evoked potentials were recorded from a midline scalp electrode, using a series of 50 rapid balloon inflations with 13 ml of air. Peak to peak amplitudes (N1-P1, P1-N2) and peak latencies (N1, P1, N2) were assessed. Inverse correlations were found between age and N1-P1 amplitude (P < 0.05), and between age and P1-N2 amplitudes (P < 0.05). N1 and P1 latencies were significantly longer in elderly patients (N1: P < 0.05; P1: P < 0.05). Amplitudes and peak latencies of cerebral potentials evoked by balloon distension of the oesophagus are age-dependent. In cerebral evoked potential studies, patients and healthy controls should be age-matched.

Acute effects of nitric oxide on left ventricular relaxation and diastolic distensibility in humans. Assessment by bicoronary sodium nitroprusside infusion.

In isolated mammalian cardiomyocytes, papillary muscle preparations, and ejecting hearts, nitric oxide (NO) or other cyclic GMP-elevating interventions increase diastolic cell length and reduce peak contractile performance by hastening onset of myocardial relaxation. In the present study, the effect of NO on left ventricular (LV) relaxation and diastolic distensibility was investigated in humans. The NO donor substance sodium nitroprusside was infused during cardiac catheterization in the global coronary bed of the LV of patients (n = 13) investigated for chest pain who were without evidence of obstructive coronary artery or other cardiac disease. Sodium nitroprusside was infused intracoronarily at a dosage (< or = 4 micrograms/min) that was previously shown to be devoid of systemic effects when infused into the brachial artery to investigate the reactivity of the forearm vascular bed. The effect of this global intracoronary infusion of the NO donor sodium nitroprusside was assessed by sequential LV angiograms and tip-micromanometer pressure recordings. During global intracoronary nitroprusside infusion, there was a decrease in heart rate from 78 +/- 11 to 76 +/- 12 beats per minute (P < .05), in LV peak systolic pressure from 161 +/- 18 to 146 +/- 18 mm Hg (P < .001), and in time to onset of LV relaxation (interval from Q wave on the ECG to LV dP/dtmin) from 432 +/- 36 to 419 +/- 36 milliseconds (P < .01). In 7 patients in whom adequate sequential LV angiograms could be obtained, LV end-diastolic volume increased from 158 +/- 34 to 165 +/- 40 mL (P < .05), whereas LV end-diastolic pressure fell from 18 +/- 5 to 12 +/- 3 mm Hg (P < .02), and in 5 of these 7 patients, a downward shift of the diastolic LV pressure-volume relation was observed. In 5 patients, a right atrial infusion of sodium nitroprusside was performed either before (n = 2) or after the global intracoronary infusion. The decrease in LV peak systolic pressure observed during right atrial infusion was significantly smaller (P < .01) than during global intracoronary infusion. The present study reveals reduced LV pressure development, an LV relaxation-hastening effect, and improved LV diastolic distensibility during global intracoronary infusion of the NO donor substance sodium nitroprusside. These effects appeared to be unrelated to systemic vasodilation or to pericardial constraint and could be explained by a direct myocardial effect of NO, probably through activation of guanylyl cyclase to increase cyclic GMP or through modification of other cellular proteins.

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.

Intravascular ultrasound study of the impact of atherosclerosis on the in vivo regional and segmental arterial distensibility in humans: Importance of atheroma composition

Intravascular ultrasound study of the impact of atherosclerosis on the in vivo regional and segmental arterial distensibility in humans: Importance of atheroma composition

Cerebral electrical potentials evoked by balloon distention of the human esophagus

Cerebral evoked potentials provide a technique for evaluation of central nervous processing of information derived from a variety of sensory modalities. Evoked potentials associated with balloon distention of the smooth muscle esophagus were studied in 14 adult volunteers. Stimulation was applied via repeated inflation and deflation of a balloon attached to a pressure pump that cycled at 0.2 Hz. Cortical electrical responses were recorded from scalp electrodes at Cz, Cz′, and Pz of the international 10–20 System for electroencephalographic recording. The recording electrodes were referenced to Fpz and averaged over a 1-s period for 100 repetitions. Latencies, amplitudes, and waveforms of the evoked potentials were compared with controls consisting of pump on/balloon detached, auditory masking, and conventional somatosensory posterior tibial nerve stimulation. Polyphasic evoked potentials were obtained in all subjects, and maximum positive deflections occurring with latencies of 202–396 ms. Maximal amplitudes ranged from 2.5–8.3 μV. Latencies and amplitudes of the evoked responses were highly reproducible in each subject with considerable variation among subjects. Conclusions: (a) Reproducible evoked potentials with distinctive waveforms can be recorded in response to esophageal balloon distention in humans; (2) long latency of the evoked potentials suggests involvement of nonmyelinated visceral afferent pathways; (3) the evoked potentials are probably specific to mechanical stimulation rather than being nonspecific arousal responses; and (4) the results support this as a promising new method for investigation of the neurobiology of gastrointestinal sensation in humans that may help clarify pathological conditions of the irritable esophagus syndrome and esophagus-related chest pain.

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.

Sympathetic activity and blood pressure increases with bladder distension in humans.

Microneurographic recordings of muscle nerve sympathetic activity, which is governed by baroreceptors and involved in blood pressure regulation, were made in the peroneal nerve in 16 healthy volunteers during physiological bladder distension. When the urge to urinate was pronounced, sympathetic outflow increased from a baseline level of 16.3 +/- 1.7 to 23.2 +/- 1.9 bursts/min (mean +/- SEM, p less than 0.01). There was a concomitant significant rise in both systolic and diastolic blood pressure, from 125 +/- 2/74 +/- 2 to 140 +/- 4/84 +/- 3 mm Hg. After micturition, sympathetic activity and blood pressure returned toward initial values. It is concluded that 1) increased sympathetic outflow contributed to the rise in blood pressure, 2) there is a vesicovascular response mediated by sympathetic vasoconstrictor neurons in humans corresponding to mechanisms observed in animals, and 3) the described functional relation between bladder distension and sympathetic vasoconstrictor activity probably plays a role in clinical conditions such as autonomic dysreflexia in humans with cervical spinal cord lesions and nocturnal micturition syncope.

Vasopressin is secreted in response to systemic infusion of cholecystokinin but not gastric distension in humans

Vasopressin is secreted in response to systemic infusion of cholecystokinin but not gastric distension in humans

Neurohypophyseal secretion in response to cholecystokinin but not meal-induced gastric distention in humans.

Exogenous administration of cholecystokinin octapeptide (CCK) is known to decrease food intake and slow gastric emptying in humans and animals. Recent studies have shown that CCK stimulates neurohypophyseal secretion of oxytocin (OT) in rats and arginine vasopressin (AVP) in monkeys, and that gastric distention also stimulates OT release in rats. We therefore studied AVP and OT secretion in 14 normal subjects in response to meal-induced gastric distention and administration of CCK, both separately and in combination, to assess whether these stimuli similarly activated central neurohypophyseal pathways in humans. Neither plasma AVP nor OT concentrations increased after gastric distention produced by ingestion of a large meal. However, a dose-related increase in plasma AVP, but not OT levels, occurred after CCK administration, the threshold CCK dose being 0.05 micrograms/kg body weight. The AVP secretion in response to CCK administration was significantly correlated with subjective aversive symptoms quantified by use of a numeric scale (r = 0.61, P less than 0.001). In 12 of the 14 subjects plasma AVP levels increased in association with symptoms of epigastric pressure and discomfort before the onset of overt nausea or emesis. The combination of CCK and meal-induced gastric distention did not stimulate increases in plasma AVP levels in excess of those produced by CCK administration alone. The results demonstrate that AVP secretion resulting from emetic center activation often is a graded response that can begin in association with milder degrees of visceral discomfort before symptoms of overt nausea or emesis. In addition, the stimulation of AVP secretion by CCK administration, but not by meal-induced gastric distention in association with physiological satiety, suggests that some component of the anorectic effects of exogenous CCK in man likely results from activation of brainstem emetic centers.

Effect of Atropine on Gastrin Release Stimulated by an Amino Acid Meal in Humans

Previous reports indicate that atropine enhances gastrin release stimulated by sham feeding or gastric distention in humans, suggesting that cholinergic mechanisms normally inhibit the gastrin responses to these stimuli. To investigate cholinergic regulation of gastrin release stimulated by dietary amino acids, we measured serum gastrin levels in healthy human beings before and after intragastric infusion of an amino acid meal and parenteral injection of one of four doses of atropine or saline. Following infusion of the meal, intragastric pH was held constant at 5.0 by in vivo intragastric titration, and gastric emptying was assessed by an indicator dilution method. Small intravenous doses of atropine (0.78 and 2.3 μg/kg) reduced amino acid mealstimulated gastrin release in every subject. For example, 2.3 μg/kg atropine reduced the average (±SE) gastrin response to the meal from 71 ± 15 to 53 ± 11 pglml in 10 subjects (p

Adrenergic regulation of distention-induced gastrin release in humans

To investigate the possible role of adrenergic nerves in neurally mediated gastrin release, we evaluated the effect of selective adrenergic blockade on the serum gastrin response to gastric distention in healthy human subjects. On separate days, 2 mg of propranolol (β-adrenergic antagonist), 5 mg of phentolamine (α-adrenergic antagonist), or saline (control) was injected intravenously just before distending the stomach with 700 ml of isotonic saline. For 30 min following distention, intragastric pH was kept constant at 5.0 by in vivo titration. Propranolol reduced distention-induced gastrin release by approximately 90% (p < 0.02), whereas phentolamine had no significant effect on the gastrin response to distention. In additional experiments, we evaluated the effect of the same doses of propranolol or phentolamine on the exaggerated gastrin response to gastric distention that occurred during cholinergic blockade with atropine. In the presence of atropine (2.3 μg/kg i.v.), propranolol significantly (p < 0.01) reduced distention-induced gastrin release, whereas phentolamine significantly enhanced the gastrin response to distention (p < 0.01). We conclude that: 1.(1) distention-induced gastrin release was reduced by propranolol, suggesting that gastric distention releases gastrin by a β-adrenergic mechanism and2.(2) distention-induced gastrin release was enhanced by phentolamine, but only in the presence of atropine. Thus, adrenergic nerves appear to regulate the gastrin response to gastric distention in humans: β-adrenergic pathways stimulate gastrin release, and α-adrenergic pathways may inhibit gastrin release under certain circumstances.