Mechanisms Of Gastroesophageal Reflux Research Articles

Mechanism of Gastroesophageal Reflux in Obstructive Sleep Apnea: Airway Obstruction or Obesity?

This is the first study to compare reflux events during wake and sleep in obese and non-obese individuals with obstructive sleep apnea (OSA) and obese individuals without OSA. The primary aim of the study was to investigate any additive effect of OSA on gastroesophageal reflux (GER) above that of obesity. Twenty obese individuals (body mass index, BMI > 30 kg/m(2)), 9 non-obese individuals (BMI < 30 kg/m(2)) with moderate-to-severe OSA, and 17 obese control subjects (BMI > 30 kg/m(2)) underwent high-resolution esophageal manometry, 24-h esophageal pH-impedance monitoring, and in-laboratory polysomnography. Mean body mass index was 40 ± 6 and 27 ± 4 kg/m(2) for the obese and non-obese OSA groups, respectively, and 34 ± 5 kg/m(2) for the obese control group. Apnea-hypopnea index (AHI) was 50 ± 30 and 30 ± 25 per hour for the obese and non-obese OSA groups (p > 0.05), significantly higher than that of the obese control group (3 ± 3 per hour, p < 0.05). The two obese groups did not show any significant differences in the total number of acidic reflux events (41 ± 20 vs 28 ± 16); however, the obese OSA group had a greater number of acidic reflux events compared to the non-obese OSA group (22 ± 12 events, p < 0.05). In multivariate analysis, BMI significantly predicted number of acidic reflux events (r(2) = 0.16, p = 0.01) during the 24-h period; however, AHI showed no significant association with any measure of GER severity. This study confirms an important role for obesity, rather than OSA per se in the relationship between OSA and GER.

Scintigraphic Analysis of the Dynamics of the Acid Pocket During Different Mechanisms of Gastroesophageal Reflux

AIM: During transient lower esophageal sphincter relaxations (TLESRs) the position of the gastric acid pocket mainly determines the acidity of the refluxate. However, to what extent the position or dynamics of the acid pocket determines acidity of the refluxate during other mechanisms of reflux (straining, low lower esophageal sphincter pressure (LESp) or during swallows) remains unclear. METHODS: Twenty patients with gastroesophageal reflux disease (GERD) were invited to undergo combined high resolution manometry (HRM) and pHimpedance recording after a standardized meal (550kcal) in the upright position. The acid pocket was visualized using scintigraphy after i.v. injection of 350MBq 99mTc-pertechnetate. The position of the pocket was classified as supradiaphramatic, extending into the hiatal opening (infradiaphragmatic) or subdiaphragmatic using radionuclide markers on the HRM catheter. The underlying reflux mechanism was determined using HRM, according to predefined criteria (v Herwaarden, Gastroenterology 2000, 1439-46). RESULTS: A total of 494 reflux episodes were detected, of which 244 (49%) were acidic. The underlying mechanism of reflux was a TLESR in 328 (66%), low LESp in 21 (4.3%), straining in 126 (26%), swallow-associated in 14 (2.9%) and unknown in 5 (1.0%) events respectively. Acidic reflux occurred with a supradiaphragmatic localisation of the acid pocket in 117 of 129 (91%) events, in 103 of 169 (62%) events with an infradiaphragmatic localisation and in 19 of 175 (11%) events with a subdiaphragmatic localisation. When straining was the underlying mechanism, the refluxate was more often acidic than during a TLESR (n=100 (80%) vs n= 130 (40%) respectively P<0.0001, Chi square). There was no difference in acidity between reflux events during low LESp or events associated to swallows compared to TLESRs. Scintigraphic imaging clearly illustrated that straining pushes the acid pocket upwards into the esophagus regardless of its initial position. CONCLUSION: Our data confirm that a supradiaphragmatic position of the acid pocket is an important factor determining the risk for acidic reflux, also during mechanisms of reflux different from TLESRs. Scinitgraphic imaging of the pocket demonstrates that the acid pocket is pushed into the esophagus during straining regardless of its position, further illustrating that the pocket is indeed the reservoir of acidic refluxate.

Beyond Acid Suppression: New Pharmacologic Approaches for Treatment of GERD

Proton pump inhibitors are highly successful in treating gastroesophageal reflux disease, but a significant proportion of patients have persistent symptoms from weakly or nonacidic reflux. Transient lower esophageal sphincter relaxation (TLESR) represents the dominant mechanism of gastroesophageal reflux and has therefore become the most intensely investigated therapeutic target. The triggering of TLESR involve the vagal pathways and the gamma-aminobutyric type B (GABA(B)) and metabotropic glutamate type 5 (mGluR5) receptors. Baclofen is a GABA(B) receptor agonist that is effective in inhibiting TLESR and reducing the number of reflux episodes, but is associated with significant central nervous system (CNS) side effects. The newer GABA(B) agonists, such as AZD9343 and AZD3355, and mGluR5 antagonists, such as 2-methyl-6-(phenylethynyl)-pyridine (MPEP), have been shown in small, randomized, controlled trials to have comparable efficacy to baclofen, but possibly a more favorable CNS side effect profile. Cannibinoid agonists, such as Delta(9)-THC, have also been demonstrated to reduce TLESRs and reflux events respectively. Macrolide antibiotics (eg, erythromycin) show early promise in a select group of patients with possible reflux associated post-lung transplant problems.

Mechanism of gastroesophageal reflux in patients with obstructive sleep apnea syndrome

It has been reported that the prevalence of gastroesophageal reflux (GER) disease is high in patients with obstructive sleep apnea (OSA). End-inspiratory intra-esophageal pressure decreases progressively during OSA, which has been thought to facilitate GER in OSA patients. The aim of our study was to clarify the mechanisms of GER during sleep (sleep-GER) in OSA patients. Eight OSA patients with reflux esophagitis (RE), nine OSA patients without RE, and eight healthy controls were studied. Polysomnography with concurrent esophageal manometry and pH recording were performed. Significantly more sleep-GER occurred in OSA patients with RE than without RE or in controls (P < 0.05). The severity of OSA did not differ between OSA patients with RE and without RE. Sleep-GER was mainly caused by transient lower esophageal sphincter relaxation (TLESR), but not by negative intra-esophageal pressure during OSA. During OSA gastroesophageal junction pressure progressively increased synchronous to intra-esophageal pressure decrease. OSA patients had significantly more TLESR events during sleep related to preceding arousals and shallow sleep, but the number of TLESR events was not related to RE. In OSA patients, sleep-GER was mainly caused by TLESR, but not by negative intra-esophageal pressure due to OSA.

Mechanisms of gastroesophageal reflux in children with sequelae of birth asphyxia

Patterns of childhood gastroesophageal reflux (GER) have been studied extensively; however, the mechanisms underlying its occurrence in neurologically impaired children (NIC) are poorly understood. Concurrent esophageal manometry and pH monitoring was conducted in 10 un-operated children (7 male; mean age: 59.5 months) with sequelae birth asphyxia and esophagitis. Reflux episodes were scored when esophageal pH decreased to <4 for at least 5 s. When the rate of decrease of lower esophageal sphincter (LES) pressure was >1 mm Hg/s, the decrease of LES pressure was defined as LES relaxation. The time relationship of the pharyngeal manometric swallowing signal to LES relaxation onset was then evaluated in order to distinguish between LES relaxations associated with swallowing (type II or III, associated with one or more swallows, respectively) and those that occurred independently of swallowing (type I). Results: Esophageal manometry and pH monitoring were conducted for a mean duration of 91.5 min. Basal LES pressure averaged (±SD) 9.2 ± 4.8 mm Hg; in 4 of 10 patients (40%) the LES pressure was largely undetectable, varying between 0 and 2 mm Hg. Mean LES pressure was inversely correlated with age ( r = 0.7, P = 0.02). The total number of reflux episodes/h averaged 32.1 ± 12.1 LES pressure reached 0 mm Hg in 98% of reflux episodes. Type I LES relaxations were present in 3.15 ± 1.1 reflux episodes/h, whereas type II LES relaxation occurred in 2.3 ± 2.4 episodes/h. Acid reflux episodes appeared during absent basal LES tone periods, without phasic LES relaxations, in 74%. Conclusions: Absent basal LES tone is the main mechanism of GER in a subgroup of NIC, especially in older children. Transient LES relaxation, the most common known event associated with acid reflux in neurologically normal children, seems to precede a minority of reflux events in NIC.

Mechanisms of Acid Gastroesophageal Reflux in the Japanese Population

In contrast to Western countries, reflux esophagitis is considered to be less common in the Orient, including Japan. Transient LES relaxation (TLESR) is a major mechanism of gastroesophageal reflux (GER); however, there are no data on the mechanisms of GER in Japanese people. In addition, it is unclear whether or not the rate of TLESRs, in the sitting position, is higher in reflux esophagitis patients than in healthy subjects. The aim of this study is to determine the mechanisms of acid reflux and the rate of TLESRs, and to compare the rate of acid reflux during TLESRs between healthy volunteers and patients with reflux esophagitis in Japan. Preprandial and postprandial esophageal manometry and pH monitoring were performed in the sitting position in ten healthy volunteers and ten patients with reflux esophagitis of Los Angeles grade C. The energy level of the meal was 692 kcal and consisted of 33% fat. In healthy volunteers, 100% (median) of the acid reflux episodes occurred during TLESRs compared with 55.0% in patients with esophagitis. The remaining reflux episodes in the esophagitis patients were related to straining (12.8%) and absent basal LES pressure (19.5%). The rate of TLESRs in patients with esophagitis was 4.7 h(-1) (3.3-5.7) [median, (interquartile range)] and did not vary significantly from that in healthy volunteers [5.0 h(-1) (4.3-6.3)] 3 h postprandially. The rate of acid reflux during TLESRs in patients with esophagitis (42.7%, median) 3 h postprandially was significantly higher than in healthy volunteers (9.2%). In Japan, the mechanisms of GER in both groups are similar to those reported in Western countries. The rate of acid reflux during TLESRs in patients with reflux esophagitis is significantly higher than in healthy volunteers; however, compared to rates reported in Western countries these rates are very low for both groups.

Esophageal motor disorders: recent advances

The aim of this article is to highlight literature published during the last year in the context of previous knowledge. A number of novel techniques - high-resolution manometry, esophageal electrical impedance and intra-luminal ultrasound imaging - have improved our understanding of esophageal function in health and disease. Several studies address the function of longitudinal muscle layer of the esophagus in normal subjects and patients with motor disorders of the esophagus. Esophageal electrical impedance recordings reveal abnormal transit in patients with diffuse esophageal spasm, achalasia and patients with normal manometry. Loss of the mammalian Sprouty2 gene leads to enteric neuronal hyperplasia and esophageal achalasia. Several studies showed excellent long-term results of medical and surgical treatment of achalasia of the esophagus. For the first time, mechanisms of gastroesophageal reflux in critically ill mechanically ventilated patients are reported. Novel pharmacologic strategies in the treatment of reflux disease are highlighted. Several novel techniques, perfected during recent years, have improved our understanding of esophageal function and dysfunction. A number of important observations, reviewed here, provide important insight into the pathogenesis of esophageal motor disorders and treatment of gastroesophageal reflux disease.

Mechanisms of Gastroesophageal Reflux in Critically Ill Mechanically Ventilated Patients

Mechanisms of Gastroesophageal Reflux in Critically Ill Mechanically Ventilated Patients

Inhibition of Transient Lower Esophageal Sphincter Relaxation and Gastroesophageal Reflux by Metabotropic Glutamate Receptor Ligands

Transient lower esophageal sphincter relaxation (TLESR) is the major mechanism of gastroesophageal acid reflux. TLESR is mediated via vagal pathways, which may be modulated by metabotropic glutamate receptors (mGluRs). Group I mGluRs (mGluR1 and 5) have excitatory effects on neurons, whereas group II (mGluR2 and 3) and group III (mGluR4, 6, 7, and 8) are inhibitory. This study determined the effect of mGluRs on triggering of TLESR and reflux in an established conscious ferret model. Esophageal manometric/pH studies were performed in ferrets with chronic esophagostomies. TLESR were induced by a gastric load of 25 mL glucose (pH 3.5) and 30 mL air. In control treated animals, gastric load induced 3.52 +/- 0.46 TLESRs per 47-minute study, 89.7% of which were associated with reflux episodes (n = 16). The mGluR5 antagonist MPEP inhibited TLESR dose dependently, with maximal 71% +/- 7% inhibition at 35 micromol/kg (n = 9; P < .0001). MPEP also significantly reduced reflux episodes (P < .001) and increased basal lower esophageal sphincter pressure (P < .05). MPEP inhibited swallowing dose dependently, suggesting a common action on trigger mechanisms for swallowing and TLESR. The more selective analogue, MTEP, had more potent effects (90% +/- 6% inhibition TLESR at 40 micromol/kg; n = 8; P < .0001). In contrast, the group I agonist DHPG tended to increase TLESR. The group II agonist (2R, 4R)-APDC was ineffective, whereas the group III agonist L-(AP4 slightly reduced TLESR (33% at 11 micromol/kg; P < .05). The selective mGluR8 agonist (S)-3, 4-DCPG inhibited TLESR by 54% at 15 micromol/kg (P < .01). mGluR5 antagonists potently inhibit TLESR and reflux in ferrets, implicating mGluR5 in the mechanism of TLESR. mGluR5 antagonists are therefore promising as therapy for patients with GERD.

Mechanisms of gastroesophageal reflux in critically ill mechanically ventilated patients

Gastroesophageal reflux is a major problem in mechanically ventilated patients and may lead to pulmonary aspiration and erosive esophagitis. Transient lower esophageal sphincter relaxations are the most common mechanism underlying reflux in nonventilated patients. The mechanisms that underlie reflux in critically ill ventilated patients have not been studied. The aim of this study was to determine the mechanisms underlying gastroesophageal reflux in mechanically ventilated patients in the intensive care unit. In 15 mechanically ventilated intensive care unit patients, esophageal motility, pH, and intraluminal impedance (11/15 patients) were recorded for 1 hour before and 5 hours during continuous nasogastric feeding. Basal lower esophageal sphincter pressure was uniformly low (2.2 +/- 0.4 mmHg). The median (interquartile range) acid exposure (pH <4) was 39.4% (0%-100%) fasting and 32% (7.5%-94.2%) fed. Acid reflux occurred in 10 patients, but slow drifts in esophageal pH were also an important contributor to acid exposure. If esophageal pH decreased to pH <4, it tended to remain so for prolonged periods. A total of 46 acid reflux events were identified. Most (55%) occurred because of absent lower esophageal sphincter pressure alone; 45% occurred during straining or coughing. Gastroesophageal reflux in mechanically ventilated patients is predominantly due to very low or absent lower esophageal sphincter pressure, often with a superimposed cough or strain. These data suggest that measures that increase basal LES pressure may be useful to prevent reflux in ventilated patients.

Gastroesophageal Reflux in the Preterm Neonate

After completing this article, readers should be able to: 1. Describe the epidemiology and pathophysiology of gastroesophageal reflux (GER) in preterm neonates. 2. Delineate the associations of GER with apnea, chronic lung disease, behavior, and growth of preterm infants. 3. Review the investigations used to evaluate GER in preterm infants. 4. Describe nonpharmacologic and pharmacologic therapies for GER. Gastroesophageal reflux (GER) is a normal physiologic event occurring across the age spectrum. It may contribute to a variety of disorders, including esophagitis, feeding problems, and airway disease in all age groups. (1) A large number of symptoms and signs have been purported to be caused by GER despite a lack of data showing a clear association between a specific symptom and GER. In preterm infants, empiric therapy often is administered using agents of unproven efficacy and safety to treat symptoms that likely are unrelated to GER. In a survey on management practices for GER in preterm infants, common treatment strategies included positioning (98%) and slopes (96%), histamine 2 (H 2) receptor antagonists (100%), feed thickeners (98%), antacids (96%), prokinetics (79%), proton pump inhibitors (PPIs) (65%), and dopamine receptor antagonists (53%). (2)(3) The safety, efficacy, and appropriate dosing recommendations for most medical therapies remain uncertain in neonates. In this review, we attempt to summarize the current literature regarding physiology, pathophysiology, and diagnostic and management strategies for GER pertinent to the neonate, with an emphasis on the preterm infant. GER describes the retrograde movement of stomach contents (air or feeding, liquid or semisolid, acid or alkaline, enzymes or bile salts) into the esophagus. GER disease (GERD) occurs when GER causes symptoms or signs such as pain, poor weight gain, esophagitis, hematemesis, and airway symptoms, including apnea, aspiration, recurrent pneumonia, chronic lung disease (CLD), or large airway inflammation. However, any of these symptoms or signs …

AGA technical review on the clinical use of esophageal manometry

AGA technical review on the clinical use of esophageal manometry

The role of lower esophageal sphincter function and dysmotility in gastroesophageal reflux in premature infants and in the first year of life.

Transient relaxations of the lower esophageal sphincter (tLESRs), but not delayed gastric emptying, are major mechanisms of gastroesophageal reflux in premature infants. These findings are similar to those seen in older children and adults with gastroesophageal reflux disease. Newer antireflux therapies should be developed that target the reduction of gastric acidity or reduction in the number of tLESRs.

Effect of prolonged gastric distention on lower esophageal sphincter function and gastroesophageal reflux.

Morbidly obese patients treated with an intragastric balloon report a transient increase in gastroesophageal reflux (GER) symptoms. In the present study, we evaluated the underlying mechanisms of GER and examined the effect of prolonged gastric distention on lower esophageal sphincter function. Fasting and postprandial manometric studies were performed in obese subjects (n = 15) before, immediately after, and 10 and 20 wk after placement of a 500-ml water-filled balloon. Residual lower esophageal sphincter (LES) pressure after water swallows was not affected after balloon placement, excluding mechanical interaction with sleeve function. Postprandial LES pressure was significantly increased after 10 and 20 wk. GER was increased in the right recumbent position until 10 wk after balloon placement, mainly because of an increased percentage of transient lower esophageal sphincter relaxations (TLESRs) accompanied by GER. TLESRs were the main mechanisms underlying reflux both before and after balloon placement. The rate of TLESRs was increased significantly immediately after introduction of the balloon, returning to baseline values after 20 wk. After balloon placement, reflux episodes were evoked by gastric contractions that were not inhibited by meals. Chronic distention by an intragastric balloon increased reflux up to 10 wk after placement because of an increase in the percentage of TLESRs accompanied by a reflux episode. In addition, prolonged balloon distention increased the rate of TLESRs and created a postprandial state even 10 wk after balloon placement. After 20 wk these effects largely resolved, illustrating adaptation to this artificial situation.

Effect of prolonged gastric distention on lower esophageal sphincter function and gastroesophageal reflux

Objectives Morbidly obese patients treated with an intragastric balloon report a transient increase in gastroesophageal reflux (GER) symptoms. In the present study, we evaluated the underlying mechanisms of GER and examined the effect of prolonged gastric distention on lower esophageal sphincter function. Methods Fasting and postprandial manometric studies were performed in obese subjects (n = 15) before, immediately after, and 10 and 20 wk after placement of a 500-ml water-filled balloon. Results Residual lower esophageal sphincter (LES) pressure after water swallows was not affected after balloon placement, excluding mechanical interaction with sleeve function. Postprandial LES pressure was significantly increased after 10 and 20 wk. GER was increased in the right recumbent position until 10 wk after balloon placement, mainly because of an increased percentage of transient lower esophageal sphincter relaxations (TLESRs) accompanied by GER. TLESRs were the main mechanisms underlying reflux both before and after balloon placement. The rate of TLESRs was increased significantly immediately after introduction of the balloon, returning to baseline values after 20 wk. After balloon placement, reflux episodes were evoked by gastric contractions that were not inhibited by meals. Conclusions Chronic distention by an intragastric balloon increased reflux up to 10 wk after placement because of an increase in the percentage of TLESRs accompanied by a reflux episode. In addition, prolonged balloon distention increased the rate of TLESRs and created a postprandial state even 10 wk after balloon placement. After 20 wk these effects largely resolved, illustrating adaptation to this artificial situation.

Mechanisms of gastroesophageal reflux in Japan: The rate of acid reflux during transient lower esophageal sphincter relaxation (TLESR) is very low, compared with that reported from Western countries

Mechanisms of gastroesophageal reflux in Japan: The rate of acid reflux during transient lower esophageal sphincter relaxation (TLESR) is very low, compared with that reported from Western countries

Mechanisms of gastroesophageal reflux in critically III mechanically-ventilated patients

Mechanisms of gastroesophageal reflux in critically III mechanically-ventilated patients

Morphine and transient lower esophageal sphincter relaxation (TLESR): Relevance of fundic mechanoreceptors

Background and aim: TLESR is a major mechanism of gastroesophageal reflux. It has been previously shown that morphine decreases the rate of TLESRs, the volume of the proximal stomach and the number of its contractions (Gastroenterology 2000;118:A860). h is presently unknown if the effect on TLESRs depends on those exerted on the stomach, and in this case if it is due to a decrease in stimulation of stretch receptors (~, in gastric volume) or tension receptors (J. in the number of contractions). Our aim was to assess the effect of morphine on the rate of TLESRs and motor function of the proximal stomach in a lsovohimetric model of gastric distension (which does not modify stimulation of stretch receptors). Methods: 10 healthy subjects, 6 men, aged 21-30 yrs, were studied using a multihimen assembly recording pressures in the phaqmx, esophageal body, lower esophageal sphincter (Dentaleeve), stomach and a bag catheter positioned in the proximal stomach and connected to a harostat, lntrabag volume was set at 75% of the threshold volume for gastric discomfort and maintained for two 35-min distension periods separated by 45-min washout with the bag deflated. At the beginmng of the second distension morphine 100 p.g/kg iv as a bolus was administered, lntrabag fIB) baseline pressure and pressure waves (->3 mmHg) were evaluated as a measure of tone and phasic contractions in the proximal stomach respectively. Results (means -+ gEM): IB volume was 502 -+ 32 ml. See table. Conclusions: in a isovolumetnc model of gastric distension morphine decreases stimulation of tension receptors by inhibiting gasmc contractions, but it does not affect the rate of TLESRs, suggesting that a decrease in volume of the proximal stomach 0. in stretch receptor stimulation) is essential for its effect on TLESRs. Pharmacological interventions which decrease the volume of the proximal stomach should result in control of TLESR-mediated gastroesophageal reflux.

Mechanism of gastroesophageal reflux in premature infants with chronic lung disease

Background/Purpose: The aim of this study was to characterize the motor events responsible for gastroesophageal reflux (GER) and esophageal acid clearance in a cohort of preterm infants with chronic lung disease (CLD). Methods: Esophageal motility was recorded for 2 to 3 hours postprandially in 14 preterm infants with mild-moderate or moderate-severe CLD at 33 to 39 weeks postmenstrual age using a sleeve-side hole micromanometric assembly into which a pH probe had been installed. Results: Twenty-six acid GER episodes were recorded by pH probe. Of these, 22 (85%) were associated with transient lower esophageal sphincter (LES) relaxation. Transient LES relaxations were significantly longer in duration than single swallows (13.7 seconds v 4.6 seconds, P < .001) and had lower nadir pressures (1.1 mm Hg v 2.5 mm Hg, P < .001). During periods of esophageal acidification (pH below 4), peristaltic esophageal body pressure wave sequences cleared acid refluxate more effectively than nonperistaltic pressure wave sequences. Conclusions: In preterm infants with CLD, transient LES relaxations are the predominant mechanism underlying GER, and esophageal clearance mechanisms are fully functional, which is similar to that seen in healthy preterm infants.

Esophageal Motor Function and Mechanisms of Gastroesophageal Reflux in the Extremely Premature Neonate

Esophageal Motor Function and Mechanisms of Gastroesophageal Reflux in the Extremely Premature Neonate