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Patterns of gas and liquid reflux during transient lower oesophageal sphincter relaxation: a study using intraluminal electrical impedance.

ABSTRACT: BACKGROUND: Belching has been proposed as a major mechanism underlying acid gastro-oesophageal reflux in normal subjects. However, the presence of oesophageal gas has not been measured directly but only inferred from manometry. AIMS: To investigate, using intraluminal electrical impedance, the patterns of gas and liquid reflux during transient lower oesophageal sphincter (LOS) relaxations, the main mechanism of acid reflux in normal subjects. METHODS: Impedance changes associated with the passage of gas were studied in vitro, and in vivo in cats. Oesophageal manometry, pH, and intraluminal electrical impedance measurements were performed in 11 normal subjects after a meal. RESULTS: Gas reflux caused a sudden increase in impedance that propagated rapidly to the proximal oesophagus whereas liquid reflux induced a retrogressively propagated fall in impedance. Impedance showed gas or liquid reflux during most (102/141) transient LOS relaxations. When acid reflux occurred, impedance showed evidence of intraoesophageal retrograde flow of liquid in the majority (78%) of events. Evidence of gas retroflow was found in almost half (47%) of acid reflux episodes. When present together, however, liquid preceded gas on 44% of occasions. Overall, gas reflux occurred as the initial event in only 25% of acid reflux episodes. CONCLUSIONS: These findings suggest that in upright normal subjects, although belching can precipitate acid reflux, most acid reflux occurs as a primary event.

SUBMITTER: Sifrim D

PROVIDER: S-EPMC1760051 | biostudies-other | 1999 Jan

REPOSITORIES: biostudies-other

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Effect of atropine on gastro-oesophageal reflux and transient lower oesophageal sphincter relaxations in patients with gastro-oesophageal reflux disease.

Project description:BACKGROUND: Atropine reduces the rate of reflux episodes in normal subjects by inhibition of transient lower oesophageal sphincter (LOS) relaxations. The aim of this study was to investigate the effect of atropine on the rate and mechanisms of reflux in patients with reflux disease. METHODS: Oesophageal motility and pH were recorded for one hour after a meal in 15 patients with reflux disease. On separate days, atropine (15 micrograms/kg bolus intravenously, 4 micrograms/kg/h infusion) or saline were given and maintained for the recording period. RESULTS: Atropine significantly reduced basal LOS pressure from 7.1 (2.2) to 2.9 (1.3) mm Hg (mean (SEM)). Atropine also reduced the rate of reflux episodes from 5.0 (2.0-8.75) to 1.0 (0-6.25) per hour (median (interquartile range)) largely because of a decrease in the rate of transient LOS relaxations from 2.0 (0-4.75) to 0 (0-0) per hour and abolition of reflux during swallow induced LOS relaxation. There was no change in the rate of reflux episodes because of absent basal LOS pressure. CONCLUSIONS: Atropine inhibits reflux in patients with reflux disease largely by inhibition of transient LOS relaxations and swallow induced LOS relaxation. These findings suggest that pharmacological control of reflux through control of transient LOS relaxations is possible in patients with reflux disease.

| S-EPMC1727184 | biostudies-other

Preservation of postural control of transient lower oesophageal sphincter relaxations in patients with reflux oesophagitis.

Project description:INTRODUCTION: In normal subjects, transient lower oesophageal sphincter relaxations (TLOSRs) and gas reflux during belching are suppressed in the supine position. Supine reflux, however, is a feature of reflux disease. AIMS: To investigate whether postural suppression of TLOSRs and gas reflux is impaired in patients with reflux disease. PATIENTS: Ten patients with erosive oesophagitis. METHODS: Oesophageal manometry was performed during gastric distension with 750 ml carbon dioxide. Measurements were made for 10 minutes before and after distension in both sitting and supine positions. RESULTS: In the sitting position gastric distension substantially increased the rate of gas reflux (median (interquartile range)), as evidenced by increases in oesophageal common cavities from 1 (0-1)/10 min to 7 (5-10)/10 min and TLOSRs from 1 (1-1.5)/10 min to 6 (2.5-8)/10 min. However, this effect was suppressed in the supine position in all but one patient (TLOSRs 0 (0)/10 min to 1 (0-4.5)/10 min, common cavities 0 (0)/10 min to 0.5 (0-2)/10 min). CONCLUSIONS: Postural suppression of TLOSRs and gas reflux is generally preserved in reflux disease.

| S-EPMC1727412 | biostudies-other

Systematic review of the introduction and evaluation of magnetic augmentation of the lower oesophageal sphincter for gastro-oesophageal reflux disease.

Project description:BackgroundMagnetic sphincter augmentation (MSA) is reported to be an innovative alternative to antireflux surgery for patients with gastro-oesophageal reflux disease. Although used in practice, little is known about how it has been evaluated. This study aimed to systematically summarize and appraise the reporting of MSA and its introduction into clinical practice, in the context of guidelines (such as IDEAL) for evaluating innovative surgical devices.MethodsSystematic searches were used to identify all published studies reporting MSA insertion. Data collected included patient selection, governance arrangements, surgeon expertise, technique description and outcome reporting.ResultsSearches identified 587 abstracts; 39 full-text papers were included (1 RCT 5 cohort, 3 case-control, 25 case series, 5 case reports). Twenty-one followed US Food and Drug Administration eligibility criteria for MSA insertion. Twenty-six documented that ethical approval was obtained. Two reported that participating surgeons received training in MSA; 18 provided information about how MSA insertion was performed, although techniques varied between studies. Follow-up ranged from 4?weeks to 5?years; in 14 studies, it was less than 1?year.ConclusionMost studies on MSA lacked information about patient selection, governance, expertise, techniques and outcomes, or varied between studies. Currently, MSA is being used despite a lack of robust evidence for its effectiveness.

| S-EPMC6972716 | biostudies-literature

Atropine inhibits gastric distension and pharyngeal receptor mediated lower oesophageal sphincter relaxation.

Project description:BACKGROUND: Atropine decreases the frequency of transient lower oesophageal sphincter relaxation (TLOSR) through an unknown mechanism. Gastric distension and pharyngeal receptor excitation are two possible sources for the afferent stimulus responsible for TLOSR. AIMS: To determine whether atropine affects gastric distension induced TLOSR and pharyngeal receptor mediated lower oesophageal sphincter (LOS) relaxation. METHODS: Oesophageal manometry and pH recordings were performed in 10 healthy volunteers on two separate days in the postprandial setting, following either atropine (15 micrograms/kg intravenous bolus and 4 micrograms/kg/h as a maintenance dose) or placebo. Pharyngeal receptor mediated LOS relaxation was studied in nine subjects by rapid injection of minute amounts of water (0.05, 0.1, 0.2, 0.3, and 0.4 ml) in the pharynx before and after atropine. Gastric distension mediated TLOSR was studied in eight subjects by insufflating the stomach with 300, 600 and 900 ml of CO2 before and after atropine. RESULTS: Atropine reduced the frequency of spontaneous gastro-oesophageal reflux and TLOSR compared with placebo (p < 0.05). Pharyngeal stimulation resulted in bolus volume dependent LOS relaxation. Atropine decreased the frequency and amplitude of pharyngeal receptor mediated LOS relaxation at bolus volumes of 0.05, 0.1, and 0.2 ml. Gastric distension resulted in intermittent episodes of TLOSR. The frequency of gastric distension induced TLOSR was significantly decreased by atropine. CONCLUSION: (1) Atropine reduces the frequency of spontaneous reflux and TLOSR in normal subjects; and (2) gastric distension induced TLOSR and pharyngeal receptor mediated LOS relaxation is inhibited by atropine.

| S-EPMC1891504 | biostudies-other

Validation of Pharyngeal Acid Reflux Episodes Using Hypopharyngeal Multichannel Intraluminal Impedance-pH.

Project description:Background/aimsHypopharyngeal multichannel intraluminal impedance-pH (HMII-pH) technology incorporating 2 trans-upper esophageal sphincter impedance channels has been developed to detect pharyngeal reflux. We used the HMII-pH technique to validate the candidate pharyngeal acid reflux (PAR) episodes based on the dual-pH tracings and determined the interobserver reproducibility.MethodsWe conducted a cross-sectional study in tertiary centers in Taiwan. Ninety patients with suspected laryngopharyngeal reflux and 28 healthy volunteers underwent HMII-pH test when off acid suppressants. Candidate PAR episodes were characterized by pharyngeal pH drops of at least 2 units and reaching a nadir pH of 5 within 30 seconds during esophageal acidification. Two experts manually independently identified candidate PAR episodes based on the dual-pH tracings. By reviewing the HMII-pH tracings, HMII-pH-proven PAR episodes were subsequently confirmed. The consensus reviews of HMII-pH-proven PAR episodes were considered to be the reference standard diagnosis. The interobserver reproducibility was assessed.ResultsA total of 105 candidate PAR episodes were identified. Among them 84 (80.0%; 95% CI, 71.0-87.0%) were HMII-pH-proven PAR episodes (82 in 16 patients and 2 in 1 healthy subject). Patients tended to have more HMII-pH-proven PAR episodes than healthy controls (median and percentile values [25th, 75th, and 95th percentiles]: 0 [0, 0, 3] vs 0 [0, 0, 0], P = 0.067). The concordance rate in diagnosing HMII-pH-proven PAR episodes between 2 independent observers was 92.2%.ConclusionOur preliminary data showed that 80.0% (71.0-87.0%) of the proposed candidate PAR episodes were HMII-pH-proven PAR episodes, among which the interobserver reproducibility was good.

| S-EPMC9837550 | biostudies-literature

Regulation of basal tone, relaxation and contraction of the lower oesophageal sphincter. Relevance to drug discovery for oesophageal disorders.

Project description:The lower oesophageal sphincter (LOS) is a specialized region of the oesophageal circular smooth muscle that allows the passage of a swallowed bolus to the stomach and prevents the reflux of gastric contents into the oesophagus. The anatomical arrangement of the LOS includes semicircular clasp fibres adjacent to the lesser gastric curvature and sling fibres following the greater gastric curvature. Such anatomical arrangement together with an asymmetric intrinsic innervation and distinct proportion of neurotransmitters in both regions produces an asymmetric pressure profile. The LOS tone is myogenic in origin and depends on smooth muscle properties that lead to opening of L-type Ca(2+) channels; however it can be modulated by enteric motor neurons, the parasympathetic and sympathetic extrinsic nervous system and several neurohumoral substances. Nitric oxide synthesized by neuronal NOS is the main inhibitory neurotransmitter involved in LOS relaxation. Different putative neurotransmitters have been proposed to play a role together with NO. So far, only ATP or related purines have shown to be co-transmitters with NO. Acetylcholine and tachykinins are involved in the LOS contraction acting through acetylcholine M(3) and tachykinin NK(2) receptors. Nitric oxide can also be involved in the regulation of LOS contraction. The understanding of the mechanisms that originate and modulate LOS tone, relaxation and contraction and the characterization of neurotransmitters and receptors involved in LOS function are important to develop new pharmacological tools to treat primary oesophageal motor disorders and gastro-oesophageal reflux disease.

| S-EPMC2267263 | biostudies-other

Different in vitro and in vivo profiles of substituted 3-aminopropylphosphinate and 3-aminopropyl(methyl)phosphinate GABA(B) receptor agonists as inhibitors of transient lower oesophageal sphincter relaxation.

Project description:Background and purposeGastro-oesophageal reflux is predominantly caused by transient lower oesophageal sphincter relaxation (TLOSR) and GABA(B) receptor stimulation inhibits TLOSR. Lesogaberan produces fewer CNS side effects than baclofen, which has been attributed to its affinity for the GABA transporter (GAT), the action of which limits stimulation of central GABA(B) receptors. To understand the structure-activity relationship for analogues of lesogaberan (3-aminopropylphosphinic acids), and corresponding 3-aminopropyl(methyl)phosphinic acids, we have compared representatives of these classes in different in vitro and in vivo models.Experimental approachThe compounds were characterized in terms of GABA(B) agonism in vitro. Binding to GATs and cellular uptake was done using rat brain membranes and slices respectively. TLOSR was measured in dogs, and CNS side effects were evaluated as hypothermia in mice and rats.Key results3-Aminopropylphosphinic acids inhibited TLOSR with a superior therapeutic index compared to 3-aminopropyl(methyl)phosphinic acids. This difference was most likely due to differential GAT-mediated uptake into brain cells of the former but not latter. In agreement, 3-aminopropyl(methyl)phosphinic acids were much more potent in producing hypothermia in rats even when administered i.c.v.Conclusions and implicationsAn enhanced therapeutic window for 3-aminopropylphosphinic acids compared with 3-aminopropyl(methyl)phosphinic acids with respect to inhibition of TLOSR was observed and is probably mechanistically linked to neural cell uptake of the former but not latter group of compounds. These findings offer a platform for discovery of new GABA(B) receptor agonists for the treatment of reflux disease and other conditions where selective peripheral GABA(B) receptor agonism may afford therapeutic effects.

| S-EPMC3372828 | biostudies-literature

Esophageal Bolus Transit in Newborns with Gastroesophageal Reflux Disease Symptoms: A Multichannel Intraluminal Impedance Study.

Project description:PURPOSE:The aim of this study was to evaluate bolus transit during esophageal swallow (ES) and gastroesophageal reflux (GER) events and to investigate the relationship between the characteristics of ES and GER events in a population of term and preterm newborns with symptoms of gastroesophageal reflux disease (GERD). METHODS:The study population consisted of term and preterm newborns referred to combined multichannel intraluminal impedance (MII) and pH monitoring for GERD symptoms. The frequency and characteristics of ES and GER events were assessed by two independent investigators. Statistical significance was set at p<0.05. RESULTS:Fifty-four newborns (23 preterm) were included in the analyses. Median bolus head advancing time corrected for esophageal length (BHATc) was shorter during mealtime than during the postprandial period (median, interquartile range): 0.20 (0.15-0.29) s/cm vs. 0.47 (0.39-0.64) s/cm, p<0.001. Median bolus presence time (BPT) was prolonged during mealtime: 4.71(3.49-6.27) s vs. 2.66 (1.82-3.73) s, p<0.001. Higher BHATc (p=0.03) and prolonged BPT (p<0.001) were observed in preterm newborns during the postprandial period. A significant positive correlation between BHATc and bolus clearance time was also observed (?=0.33, p=0.016). CONCLUSION:The analysis of ES and GER events at the same time by MII provides useful information to better understand the physiopathology of GERD. In particular, the analysis of BHATc during the postprandial period could help clinicians identify newborns with prolonged esophageal clearance time due to impaired esophageal motility, which could allow for more accurate recommendations regarding further tests and treatment.

| S-EPMC4712536 | biostudies-literature

Effect of increasing the fat content but not the energy load of a meal on gastro-oesophageal reflux and lower oesophageal sphincter motor function.

Project description:BACKGROUND: Although fatty foods are commonly considered detrimental in patients with reflux disease, no objective data exist that substantiate this belief. AIMS: To investigate the effect of fat on gastro-oesophageal reflux and lower oesophageal sphincter (LOS) motor activity. SUBJECTS: Thirteen healthy subjects and 14 patients with reflux disease. METHODS: Oesophageal pH, LOS, and oesophageal pressures were recorded for 180 minutes after a high fat (52% fat) and a balanced (24% fat) meal (both 3.18 MJ) on two different occasions. Eight controls and seven patients were studied in the recumbent position and the others in the sitting position. RESULTS: The percentage of time at pH less than 4 and the rate of reflux episodes were higher (p < 0.01) in the patients than in the healthy subjects (mean 14.1% versus 1.7% and 4.4/h versus 0.8/h respectively), as was the percentage of transient LOS relaxations associated with reflux (62% versus 32%, p < 0.01). The high fat meal did not increase the rate of reflux episodes nor exposure to oesophageal acid in either group regardless of body posture. The rate of transient LOS relaxations, their association with reflux, and basal LOS pressure were also unaffected. CONCLUSIONS: Increasing fat intake does not affect gastro-oesophageal reflux or oesophagogastric competence for at least three hours after a meal.

| S-EPMC1727046 | biostudies-other

Esophageal intraluminal baseline impedance is associated with severity of acid reflux and epithelial structural abnormalities in patients with gastroesophageal reflux disease.

Project description:BackgroundThe esophageal intraluminal baseline impedance may be used to evaluate the status of mucosa integrity. Esophageal acid exposure decreases the baseline impedance. We aimed to compare baseline impedance in patients with various reflux events and with different acid-related parameters, and investigate the relationships between epithelial histopathologic abnormalities and baseline impedance.MethodsA total of 229 GERD patients and 34 controls underwent 24-h multichannel intraluminal impedance and pH monitoring (MII-pH monitoring), gastroendoscopy, and completed a GERD questionnaire (GerdQ). We quantified epithelial intercellular spaces (ICSs) and expression of tight junction (TJ) proteins by histologic techniques.ResultsMean baseline values in reflux esophagitis (RE) (1752 ± 1018 Ω) and non-erosive reflux disease (NERD) (2640 ± 1143 Ω) were significantly lower than in controls (3360 ± 1258 Ω; p < 0.001 and p = 0.001, respectively). Among NERD subgroups, mean baselines in the acid reflux group (2510 ± 1239 Ω) and mixed acid/weakly acidic reflux group (2393 ± 1009 Ω) were much lower than in controls (3360 ± 1258 Ω; p = 0.020 and p < 0.001, respectively). The mean baseline in severe RE patients was significantly lower than in mild RE patients (LA-C/D vs. LA-A/B: 970 ± 505 Ω vs. 1921 ± 1024 Ω, p < 0.001). There was a significant negative correlation between baseline value and acid exposure time (AET) (r = -0.41, p < 0.001), and a weak but significant correlation (r = -0.20, p = 0.007) between baseline value and weakly AET. Negative correlations were observed between ICS and the baseline impedance (r = -0.637, p < 0.001) and claudin-1 and the baseline impedance (r = -0.648, p < 0.001).ConclusionsPatients with dominant acid reflux events and with longer AET have low baseline impedance. Baseline values are correlated with esophageal mucosal histopathologic changes such as dilated ICS and TJ alteration.

| S-EPMC3654188 | biostudies-literature

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