Provocation of transient lower esophageal sphincter relaxations by meals in patients with symptomatic gastroesophageal reflux

The effect of a meal on the rate of transient lower esophageal sphinter (LES) relaxations and patterns of gastroesophageal reflux was investigated in 49 patients referred for evaluation of gastroesophageal reflux. Esophageal motility and pH were recorded concurrently before and after a standard meal. In the patients with symptomatic reflux, the meal induced a four-to sevenfold increase in the gastroesophageal reflux through two mechanisms: a four-to fivefold increase in the rate of transient LES relaxations and an increase in the proportion of transient LES relaxations accompanied by reflux from 47% to 68^. Overall the rate of reflux episodes that occurred by mechanisms other than transient LES relaxation did not increase significantly. An exception to these findings were those in six patients with chronically absent basal LES pressure in whom transient LES relaxations could not be scored. In these patients, reflux increased postprandially through mechanisms other than transient LES relaxation. These findings confirm the pivotal importance of transient LES relaxations in the pathogenesis of gastroesophageal reflux.     

Gastric distention: a mechanism for postprandial gastroesophageal reflux

The occurrence of gastroesophageal reflux after meals may be related to an increase in the rate of transient lower esophageal sphincter (LES) relaxations, the mechanisms of which are not understood. We investigated the effects of gastric distention on LES pressure in 16 normal subjects and 17 patients with gastroesophageal reflux disease. Intraluminal pressure was measured in the gastric fundus, LES, and esophageal body with a manometric catheter incorporating a sleeve device. Gastric distention was performed by injecting 0, 250, 500, or 750 ml of air in randomized order into a balloon and maintaining each stimulus for 15 min. Gastric distention did not significantly alter resting LES pressure in either group. During the basal period the rate of transient LES relaxation in the reflux patients (1.1 +/- 0.4 per 15 min) was greater than that in the normal subjects (0.6 +/- 0.1 per 15 min). Gastric distention resulted in a significant threefold to fourfold increase in the rate of transient LES relaxations in both groups. The reflux patients had a significantly greater proportion of complete relaxations (87%) than did the normal subjects (73%). We conclude that gastric distention, by significantly increasing the rate of transient LES relaxations in both normal subjects and patients with gastroesophageal reflux disease, may contribute to the postprandial increase in gastroesophageal reflux.     

Effect of cold stress on postprandial lower esophageal sphincter competence and gastroesophageal reflux in healthy subjects

The effect of cold stress on postprandial lower esophageal sphincter competence and gastroesophageal reflux was investigated in nine healthy subjects. All subjects were studied twice in a randomized order according to a common protocol: 30 min after completion of a 700-kcal meal they put their nondominant hand in water either at 37 degrees C (control stimulus) or at 4 degrees C (stressful stimulus) cyclically for 20 min. Pulse rate and blood pressure rose significantly (P less than 0.01) during the stressful stimulus, but remained unaffected by the control stimulus. Rate of transient lower esophageal sphincter relaxations/30 min [median (interquartile range)] was similar before and during control stimulus, 4 (2.7-5.0) and 3 (2.0-4.5), respectively, whereas it was markedly inhibited during the stressful stimulus [from 5 (3.7-6.0) to 2 (1.0-2.0); P less than 0.05 vs control stimulus]. Rate of reflux episodes/30 min was also similar before and during control stimulus, 1 (0-1.2) and 1 (1.0-2.2), but fell consistently during the stressful stimulus [from 2 (0-3.2) to 1 (0-2.0); P less than 0.05 vs control stimulus]. Percentage of transient lower esophageal sphincter relaxations accompanied by a reflux episode was unaffected by stress as was basal lower esophageal sphincter pressure. It is concluded that cold stress decreases the postprandial rate of transient lower esophageal sphincter relaxations and reflux episodes in healthy humans.     

下食管括约肌运动和功能与胃食管反流病

目的　观察胃食管反流病 (GERD)患者与对照组餐前、餐后食管pH情况 ,下食管括约肌(LES )运动模式的变化以及酸反流事件与一过性下食管括约肌松弛 (TLESR )、低LES压力 (LESP)的关系。方法　两组受试者均接受连续性 4h食管压力测定 (分别为空腹和餐后 1、2、3h)和食管pH监测 (GERD组检测 4h ,对照组检测 2 4h)。结果　GERD组酸反流事件明显高于对照组 (P <0 0 5 )。两组间TLESR发生率差异无显著性 (P >0 0 5 ) ,但与空腹比较 ,两组餐后 1h和 2hTLESR发生率明显增多 ;GERD组伴有酸反流的TLESR明显高于对照组 (P <0 0 0 1)。 4 3% (2 9/ 6 8)的酸反流事件发生在TLESR期间。 31% (2 1/ 6 8)的酸反流事件出现于低LESP状态中。结论　GERD是多因素参与的病理过程。LES运动形式变化和功能不全是GERD的重要背景因素。     

Effect of laparoscopic partial fundoplication on reflux mechanisms

OBJECTIVES: Transient lower esophageal sphincter relaxations (TLESRs) are the main mechanism causing gastroesophageal reflux. Since 1994 we have performed laparoscopic partial instead of complete fundoplication as standard surgical treatment for therapy resistant reflux disease to minimize postoperative dysphagia. To better understand the management of gastroesophageal reflux, we conducted a prospective study of the effects of laparoscopic partial fundoplication on TLESRs and other reflux mechanisms. METHODS: From 1994 to 1999, 65 patients underwent laparoscopic partial fundoplication (180-200 degrees) and 28 of these patients (16 female, 12 male, mean age 43 +/- 2 yr [range, 26-66 yr]) agreed to participate in this prospective study on reflux mechanisms. Before and 6 months after surgery, all patients were evaluated by simultaneous recording of pH and lower esophageal sphincter characteristics, using sleeve manometry. RESULTS: After partial fundoplication basal LES pressure increased significantly (p < 0.05), from 14.3 +/- 1.2 mm Hg to 17.8 +/- 1 mm Hg. Partial fundoplication significantly (p < 0.05) decreased the number of TLESRs, from 3.4 +/- 0.8 to 1.6 +/- 0.3 per hour in the fasting period, and from 4.7 +/- 0.5 to 1.9 +/- 0.3 per hour postprandially. The percentage of TLESRs associated with reflux also decreased significantly (p < 0.05), from 45 +/- 7% to 27 +/- 6% after operation. The number of reflux episodes decreased significantly (p < 0.05), from 4.1 +/- 0.7 to 1.3 +/- 0.3 per hour postoperatively. The majority of these episodes were associated with TLESRs: 57% and 46%, pre- and postoperatively, respectively. CONCLUSIONS: Laparoscopic partial fundoplication significantly increased fasting and postprandial LES pressure and significantly decreased TLESR frequency. This resulted in a significant reduction in esophageal acid exposure, with preservation of postprandial LES characteristics.     

Impact of endoscopic suturing of the gastroesophageal junction on lower esophageal sphincter function and gastroesophageal reflux in patients with reflux disease

OBJECTIVES: Plication of the gastroesophageal junction by endoscopic suturing has been reported to improve symptoms and reduce acid exposure in patients with gastroesophageal reflux disease (GERD). The mechanisms underlying these effects are not well defined. The aims of our study were to determine the impact of endoscopic suturing of the gastroesophageal junction on lower esophageal sphincter (LES) function in patients with GERD. METHODS: In 15 patients (7 males) with GERD (heartburn, % time esophageal pH < 4 greater than 4%, +/- history of erosive esophagitis within 6 months), two plications were performed circumferentially 1 cm below the gastroesophageal junction. Endoscopy and combined postprandial esophageal manometry and pH monitoring were performed before and 6 months after treatment; 24-h ambulatory pH monitoring and symptom assessment were also performed before, and at 6 and 12 months after treatment. RESULTS: Six months after treatment, the rate of transient LES relaxations (tLESRs) was decreased by 37% (p < 0.05) and basal LES pressure had increased from 4.3 +/- 2.2 mmHg to 6.2 +/- 2.1 mmHg (p < 0.05). The rate of postprandial reflux events and acid exposure time were not altered. Endoscopic suturing significantly reduced 24-h esophageal acid exposure from 9.6% (9.0-12.1) to 7.4% (3.9-10.1) at 6 months, due predominantly to a reduction in upright acid exposure. The reduction in total 24-h acid exposure was sustained to 12 months. At repeat endoscopy, only one plication was evident in 6 patients (40%) at 6 months. Seven patients (47%) remained off medications at 6 and 12 months follow-up. CONCLUSIONS: In patients with GERD, endoscopic suturing of the gastroesophageal junction results in a reduction in the rate of tLESRs, and an increase in basal LES pressure. These changes in LES function result in only a modest reduction in gastroesophageal reflux.     

Effect of intragastric volume and osmolality on mechanisms of gastroesophageal reflux in children with gastroesophageal reflux disease

OBJECTIVE: Both transient lower esophageal sphincter (LES) relaxations (TLESRs) and periods of low/absent LES pressure (LESP) are the main mechanisms of gastroesophageal reflux. These events are believed to be triggered by stimuli from different areas of the upper GI tract. We aimed at investigating the relationship between LESP profile and gastric emptying and distension after meals of different composition in 30 children with gastroesophageal reflux disease (median age 7.0 yr, range 12 months-12 yr). METHODS: Recordings of LESP and intraesophageal pH for 1 h fasting and for 2 postprandial h were performed with a perfused sleeve catheter and flexible electrode, respectively; gastric emptying and distension of antral area were simultaneously recorded with real-time ultrasonography. Ten patients had a standard meal (group A), 10 had a high-volume meal (group B), and 10 had a high-volume and osmolality meal (group C). RESULTS: Postprandial esophageal acid exposure was significantly higher in patients of groups B and C than in patients of group A (p < 0.01); it was also more prolonged in patients of group C than in subjects of group B (p < 0.05). A higher postfeeding rate of reflux episodes caused by TLESRs was detected in patients of groups B and C as compared with patients of group A (p < 0.01). This increase did not statistically differ in patients of groups B and C. Patients of group C exhibited a higher postprandial rate of reflux episodes associated with low/absent tone of the LES as well as a more prolonged gastric emptying time and a higher postfeeding gastric distension as compared with patients of groups A and B (p < 0.01). Finally, a significant correlation was only found between the postprandial rate of reflux events resulting from low/absent LESP and the degree of antral distension in patients of group C (p < 0.01). CONCLUSION: Gastroesophageal reflux is worsened by increasing the volume and osmolality of meals through significant changes of LESP. Meals of high volume and meals with high volume and osmolality cause a comparable increase of reflux episodes as a result of TLESRs. However, meals with high volume and osmolality cause the higher degrees of esophageal acid exposure than meals with high volume resulting from a higher rate of reflux episodes associated with low/absent LESP. This finding correlates with a high postfeeding antral distension.     

Effect of baclofen on gastric acid pocket in subjects with gastroesophageal reflux disease symptoms

Postprandial gastroesophageal reflux (PGER) in the distal esophagus (DE) is associated with a gastric juice ‘acid pocket’ (AP). Baclofen reduces AP extension into the DE in healthy volunteers, in part through increased lower esophageal sphincter (LES) pressure. We aimed to verify whether baclofen also affects postprandial AP location and extent in gastroesophageal reflux disease (GERD) patients. Thirteen treatment‐naive heartburn‐prevalent GERD patients underwent two AP studies, after pretreatment with baclofen 40 mg or placebo 30 minutes preprandially. We performed pH‐probe stepwise pull‐throughs (PT) (1 cm/min, LES ?10 to +5 cm) before and every 30 minutes from 30 minutes before up to 150 minutes after a test meal. After the meal, both after placebo and baclofen, gastric pH significantly dropped at 30, 60, 90 minutes postprandially (P: nadir pHs of 3.9 ± 0.6, 2.3 ± 0.6, 2.1 ± 0.4; B: nadir pHs of 2.5 ± 0.4, 2.8 ± 0.4, 2.5 ± 0.3; all P < 0.05). After placebo, LES pressure decreased at 60, 90 and 120 minutes postprandially (32.7 ± 6.1 vs. 24.5 ± 3.1, 27.3 ± 5.9, 27.3 ± 6.0 mmHg; analysis of variance [ANOVA], P = 0.037), but this was prevented by baclofen (25.4 ± 3.4 vs. 29.4 ± 2, 32.2 ± 1.4, 35.5 ± 1.7 mmHg, ANOVA, P = not significant (NS)). Baclofen did not significantly decrease the postprandial AP extent above the LES but prevented the postprandial increase in transient lower esophageal sphincter relaxations (TLESRs) (preprandial vs. postprandial, placebo: 1.1 ± 0.3 vs. 3.7 ± 0.7, P < 0.05; baclofen: 1.4 ± 0.4 vs. 2 ± 0.5, P = NS). In GERD patients, baclofen significantly increases postprandial LES pressure, prevents the increase TLESRs but, unlike in healthy volunteers, does not affect AP extension into the DE.     

Relationship between straining, transient lower esophageal sphincter relaxation, and gastroesophageal reflux in children

OBJECTIVE: Physical straining such as deep inspiration or coughing may induce gastroesophageal reflux (GER) by overcoming feeble lower esophageal sphincter (LES) pressure. The role of straining as a provocant of GER has not been analyzed systematically in children. It was our aim to examine the contribution of straining to the occurrence of GER with particular attention to its relationship to transient LES relaxations, which are a major mechanism of the occurrence of GER in pediatric patients. METHODS: Concurrent esophageal manometry and pH monitoring was performed for 4 h postprandially in six children with esophagitis (age 9 months to 12 yr). Analysis was performed on isolated single strain episodes, defined as an increased intragastric pressure > 10 mm Hg. When a drop of esophageal pH < 4.0 was noted within 15 sec after any part of a strain, this strain was defined as related to the reflux episode. RESULTS: The median value of basal LES pressure was 10 mm Hg (range 1-18). In all, 134 analyzable strains and 87 analyzable reflux episodes were recorded. Isolated strains were associated with 20 reflux episodes (23%). Reflux was observed more frequently with strains that occurred during transient LES relaxations (12/40) than straining when the LES was contracted (8/94) (p < 0.01). Sustained strain (35%) and inspiratory strain (25%) were the major patterns of straining related to reflux. CONCLUSION: Straining provoked reflux infrequently and simultaneous occurrence of straining and transient LES relaxation was important in determining the occurrence of strain-related reflux in pediatric patients with reflux esophagitis.     

The influence of rapid food intake on postprandial reflux: studies in healthy volunteers

BACKGROUND: The postprandial increase of gastroesophageal reflux (GER) results largely from an increase in the rate of transient lower esophageal sphincter relaxations (TLESRs). Gastric distension is believed to be the most important contributing factor. The aim of this study was to determine the impact of rapid food intake on GER in healthy volunteers using combined multichannel intraluminal impedance and pH (MII-pH) testing to record both acid and nonacid reflux. Our hypothesis was that rapid food intake overstresses the gastric pressure-volume response and contributes to increased postprandial GER. METHODS: Twenty healthy volunteers were included in the study. On two separate days the participants were asked to eat the same standard meal within 5 or 30 min in random order. Acid and nonacid reflux episodes were recorded over a 2-h postprandial period. RESULTS: Intake of a standard meal within 5 min was associated with more reflux episodes (median = 14) than an intake within 30 min (median = 10, p= 0.021). The increase was confined to the first postprandial hour and was caused predominantly by an increase of nonacid reflux. During the entire 2-h postprandial period, 469 reflux episodes were noted in the 40 studies. During the first postprandial hour 45% (135/303) of reflux events were nonacid as opposed to 22% (37/166) noted during the second hour (p < 0.0001). CONCLUSION: Since rapid food intake produces more GER in healthy volunteers, studies in GERD patients are warranted to evaluate if eating slowly may represent another "life-style modification" aimed at reducing GER.     

Effect of l-NMMA on Postprandial Transient Lower Esophageal Sphincter Relaxations in Healthy Volunteers

In a previous study we showed that nitric oxide (NO) synthesis inhibition by N ^G-monomethyl-l-arginine (l-NMMA) reduced the number of transient lower esophageal sphincter relaxations (TLESRs) triggered by gastric balloon distention. The role of NO in postprandial TLESRs and gastroesophageal reflux, however, is unknown. Therefore, we studied the effect of l-NMMA on meal-induced TLESRs and reflux episodes with simultaneous recording of esophageal peristalsis, intraesophageal and intragastric pH, and gastric emptying in healthy volunteers. Ingestion of a solid meal resulted in an increase in TLESRs [8.5 (6.3–11.0) 60 min] which was significantly inhibited by l-NMMA [6.0 (4.0–8.8) 60 min, P < 0.05]. In addition, the total number of reflux episodes was reduced. l-NMMA had no effect on intragastric meal distribution and gastric emptying, but attenuated the postprandial increase in intragastric pH. These results confirm the involvement of NO in the neurocircuitry underlying the triggering of TLESRs. The reduction in reflux by l-NMMA has to be confirmed in patients with gastroesophageal reflux disease. NO may be involved in the regulation of gastric acid secretion.     

Transient lower esophageal sphincter relaxations are no more frequent in patients with gastroesophageal reflux disease than in asymptomatic volunteers

OBJECTIVES: Studies of the relative frequency of transient lower esophageal sphincter relaxations (TLESRs) in patients with gastroesophageal reflux disease and asymptomatic controls have revealed conflicting data. We have therefore studied the frequency of TLESRs and the frequency and mechanisms of acid reflux episodes in patients with gastroesophageal reflux disease and age- and sex-matched asymptomatic controls using standardized criteria. METHODS: Ten patients with symptomatic gastroesophageal reflux disease (four male, aged 50 [30-59] yr) and 10 asymptomatic matched volunteers (four male, aged 50 [32-59] yr) were studied. Esophageal, lower esophageal sphincter, and gastric manometric and esophageal pH readings were recorded for 1 h before and 1 h after a 200-kcal, 150 ml long-chain triglyceride meal. RESULTS: TLESR frequency increased after the meal in both volunteers (median 0 [range = 0-3] to 3 [0-8] per hour,p < 0.01) and patients (1 [0-6] to 2.5 [0-9] per hour, p = 0.08). There was no significant difference in the frequency of TLESRs between volunteers and patients. TLESRs were more likely to be associated with acid reflux in patients (65% vs 37%, p = 0.03), whereas volunteers were more likely to reflux gas or liquid without acid (30% vs 3.0%, p = 0.01). CONCLUSIONS: TLESRs are no more frequent in patients with gastroesophageal reflux disease than age- and sex-matched asymptomatic volunteers. However, when TLESRs occur in patients, they are twice as likely to be associated with acid reflux.     

Role of CCK(A) receptors in postprandial lower esophageal sphincter function in morbidly obese subjects

To reduce weight, some morbidly obese patients are treated with an intragastric balloon, often resulting in increased reflux symptoms. As transient lower esophageal sphincter relaxations (TLESRs) are the major mechanism underlying reflux and can be reduced by cholecystokinin-A (CCK_A) blockade, we hypothesized that the CCK_A-receptor antagonist loxiglumide could reduce gastroesophageal reflux in these subjects. Postprandial manometric studies were performed in 12 obese subjects during infusion of placebo or loxiglumide. Before balloon placement, loxiglumide did not significantly reduce the rate of TLESRs but attenuated the postprandial decrease in LES pressure. After 10 weeks of balloon treatment, loxiglumide significantly reduced the rate of TLESRs. Postprandial LES pressure was significantly increased, whereas the meal-induced decrease in LES pressure was absent. Neither loxiglumide nor balloon placement affected gastroesophageal reflux. In conclusion, CCK_A receptors play an important role in post-prandial LES pressure decrease and are involved in the reflex pathway underlying the triggering of TLESRs, at least after balloon placement.     

Radiofrequency energy delivery to the gastric cardia inhibits triggering of transient lower esophageal sphincter relaxation and gastroesophageal reflux in dogs

BACKGROUND: Delivery of radiofrequency energy to the lower esophageal sphincter and gastric cardia is a new endoluminal technique proposed for the treatment of reflux disease. The mechanisms by which it achieves its effects are unclear. The study assessed the effect of radiofrequency energy delivery to the gastric cardia on the triggering of transient lower esophageal sphincter relaxations and gastroesophageal reflux in dogs. METHODS: In 13 dogs, esophageal motility and pH were measured for 1 hour after a standard liquid meal and air infusion, as well as before and 3 months after radiofrequency energy treatment. At 7 months, histologic evaluation of the gastroesophageal junction was performed. RESULTS: Radiofrequency energy delivery reduced the frequency of transient lower esophageal sphincter relaxations from 4.0 (3.0-6.75) (median [interquartile range]) per hour to 3.0 (2.0-3.0) per hour (p < 0.05). This was accompanied by a significant reduction in acid reflux episodes and esophageal acid exposure. Basal lower esophageal sphincter pressure and lower esophageal sphincter relaxation during swallowing were unchanged. There was a 63% increase in wall thickness at the gastric cardia compared with that in 2 control dogs, but no gross or histopathologic abnormalities of the esophageal or gastric mucosa. CONCLUSION: Radiofrequency energy delivery to the gastric cardia in dogs inhibits the triggering of transient lower esophageal sphincter relaxations and thereby reduces gastroesophageal reflux.     

Abolition of gas reflux and transient lower esophageal sphincter relaxation by vagal blockade in the dog

In the present study we have examined the hypothesis that transient lower esophageal sphincter relaxations are under vagal control. Fasting esophageal motor function was monitored with a manometric sleeve catheter passed via a cervical esophagostomy. Gastric insufflation with oxygen resulted in intermittent venting of gas into the esophagus during transient lower esophageal sphincter relaxations. Such venting of gas was associated with the occurrence of esophageal body common cavities and gas venting from the esophageal stoma, all of which increased with increasing rates of gastric insufflation. The optimal insufflation rate, 80 ml/min, produced stomal gas venting at a rate of 10.3 +/- 1.1/h (mean +/- SE). The time and pressure profiles of transient lower esophageal sphincter relaxations induced by gastric insufflation were similar to those relaxations seen with spontaneous postprandial gastroesophageal reflux and belching in dogs. Sphincteric relaxation started 10 s before the onset of common cavities. In all 4 dogs, cooling of cervical subcutaneous vagosympathetic loops abolished transient lower esophageal sphincter relaxations, common cavities, and stomal gas venting. Within 1-4 min of cessation of vagal cooling, all three markers of gastroesophageal gas venting returned. Atropine, 50 and 200 micrograms/kg i.v., did not block transient lower esophageal sphincter relaxations or gas reflux. Gastric gaseous distention is a potent and consistent trigger of transient lower esophageal sphincter relaxations in the dog. This effect can be used as a model for study of control mechanisms of transient sphincter relaxation-dependent gastroesophageal reflux. Our observations with this model indicate that transient lower esophageal sphincter relaxations are under vagosympathetic control, but that muscarinic mechanisms are not important mediators of this control.     

Relationship of transient lower esophageal sphincter relaxation to postprandial gastroesophageal reflux and belching in dogs

Methods have been developed for the recording of patterns of motor function associated with spontaneous gastroesophageal reflux and belching in trained, unsedated dogs. Pharyngeal, esophageal body, lower esophageal sphincter (LES), and gastric pressures were monitored in 3 dogs with a manometric assembly inserted through a cervical esophagostomy. Spontaneous changes in esophageal pH were recorded simultaneously with a glass electrode. Each dog was studied three times for 3 h starting directly after completion of a full-sized meal. Acid reflux was recorded on 40 occasions; on 35 of these occasions it was possible to analyze, in detail, motor events at the time of reflux. This analysis showed that the LES was completely relaxed at the time of reflux and that the relaxation occurred within the 15 s before the onset of esophageal acidification. In 77% of the reflux episodes LES relaxation occurred independently of swallowing or any other motor event. The remainder of the LES relaxations associated with reflux were secondary to a swallowing salvo or a single swallow that did not trigger an esophageal body peristaltic wave. Straining was associated with reflux during many episodes of LES relaxation, but did not induce reflux if there was measurable LES pressure. Belching was also related to complete LES relaxations with a pattern identical to that associated with acid reflux. In the dog, liquid and gas reflux occurred during transient LES relaxations that were very similar to those that allow reflux to occur in humans. The dog is a suitable model for investigation of the nature and control of reflux associated with transient LES relaxation.     

Characteristics and frequency of transient relaxations of the lower esophageal sphincter in patients with reflux esophagitis

Electromyogram of the submental muscles, esophageal manometry, and pH studies were simultaneously performed in an unselected group of 12 patients with subjective and objective evidence of gastroesophageal reflux (GER) disease to determine the frequency of transient relaxation of the lower esophageal sphincter (LES) and mechanisms of GER. Findings from these patients were compared with data from 10 asymptomatic healthy volunteers. Recordings were obtained for 1 h in the fasting state and 3 h after a standard 850-kcal meal. Transient relaxation of the LES was the only mechanism of acid reflux in normal subjects and accounted for 73.0% of the episodes of acid reflux in patients with GER disease. In both normal subjects and patients with GER, a large number of transient relaxations were associated at their onset with an attenuated submental EMG complex, a small pharyngeal contraction, and an esophageal contraction. The incidences of these associated events were similar in the two study populations. The frequency of transient relaxation of the LES in patients with GER was identical to that of controls. The frequency did not differ even in 9 patients with GER disease who had endoscopic esophagitis. Thirty-six percent of transient relaxations in the normal subjects were accompanied by pH evidence of reflux, but in the GER patients with endoscopic esophagitis 65% of the transient LES relaxations resulted in a reflux event. Acid reflux at the moment of deep inspiration was the second most common mechanism of GER in our patients. Four patients who demonstrated this mechanism had hiatal hernias and more severe esophagitis than the rest of the group. Our findings confirm that transient relaxation of the LES is the major mechanism of GER in patients with reflux esophagitis. However, the similar frequency of this relaxation in GER patients and in healthy asymptomatic subjects suggests that factors other than transient LES relaxation play an important role in the pathogenesis of GER disease.     

Effect of intraduodenal fat on lower oesophageal sphincter function and gastro-oesophageal reflux.

BACKGROUND AND AIMS: Fatty foods are commonly reported to aggravate gastro-oesophageal reflux symptoms. In this study the hypothesis that fat provokes reflux by stimulating transient lower oesophageal sphincter relaxations via small intestinal receptors was investigated. METHODS: In 12 healthy volunteers and 11 patients with reflux oesophagitis, oesophageal motility and pH were measured over 30 minute periods during which saline or fat (10% Intralipid) were infused in random order into the duodenum. The infusion periods were separated by a 30 minute washout. The stomach was loaded with 200 ml 10% dextrose, maintained by an intragastric infusion. RESULTS: Fat decreased basal LOS pressure from 16.9 (SEM 2.1) to 12.4 (SEM 1.5) mm Hg in normal subjects but had no effect in patients with oesophagitis (18.8 (SEM 4.3) v 18.2 (SEM 3.0) mm Hg). During saline infusion, the rates of transient lower oesophageal sphincter relaxation and reflux episodes were greater in patients (4.5 (interquartile range 2-11)/30 min and 5 (2-14)/30 min respectively) than in controls (3 (2-4)/30 min and 3 (2-3.5)/30 min respectively). Fat increased the rate of reflux episodes in the reflux patients to 6.5 (3-25)/30 min. This effect was due to an increase in the incidence of reflux during transient LOS relaxations (65% v 91%), the rate of transient relaxations remaining unchanged. CONCLUSIONS: Instillation of fat directly into the duodenum aggravates reflux in patients with reflux disease, by increasing the proportion of transient LOS relaxations accompanied by reflux.     

Composition of the postprandial refluxate in patients with gastroesophageal reflux disease

OBJECTIVE: It is not known whether the characteristics of the postprandial refluxate in patients with gastroesophageal reflux disease (GERD) differ from those observed in normal subjects. The aim of this study was to characterize the postprandial refluxate in adult patients with GERD using combined intraluminal electrical impedance and pH measurements. METHODS: Postprandial gastroesophageal reflux was assessed in 16 patients with GERD and 15 controls. pH and intraluminal electrical impedance were used to identify acid and nonacid reflux of liquid, mixed (liquid + gas) or gas. RESULTS: Transient lower esophageal sphincter relaxations (TLESRs) and reflux of gastric contents were equally frequent in both groups. However, patients with GERD had more acid reflux [8 (4.7-10.5)/h vs 3.5 (2.6-6)/h, p < 0.05], and normal subjects had more nonacid reflux [5 (4.3-6.7)/h is 3 (1-3.5)/h, p < 0.05]. Gas reflux was less frequent in GERD than in controls (51% vs 68%; p < 0.05). Pure liquid reflux, however, was more frequent (40% vs 26%, p < 0.05) and twice as likely to be acid in GERD. During TLESRs, liquid acid reflux was more frequent in GERD than in controls. CONCLUSIONS: TLESRs and reflux of gastric contents are similarly frequent in patients with GERD and controls. However, patients with GERD have more acid reflux and less nonacid reflux. Differences in the air-liquid composition of the refluxate may contribute to the higher rate of acid reflux observed in these patients.     

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.