Relationship between the mechanism of gastro-oesophageal reflux and oesophageal acid exposure in patients with reflux disease

Abstract  This study investigated the relationship between the oesophageal acid exposure time and the underlying manometric motor events in patients with gastro-oesophageal reflux disease (GORD). In 31 patients, 3-hour oesophageal motility and pH were measured after a test meal. Ten patients underwent 24-hour ambulatory manometry and pH recording. In the 3-hour postprandial study, of 367 reflux episodes 79% was associated with a transient lower oesophageal sphincter relaxation (TLOSR), 14% with absent basal lower oesophageal sphincter (LOS) pressure and the remaining 7% with other mechanisms, representing 62, 28 and 10% of the acid exposure time, respectively. Acid reflux duration per motor mechanism was longer for absent basal LOS pressure than for TLOSR (189 ± 23 s and 41 ± 5 s, respectively, P  < 0.001). In the 24-hour ambulatory study, the contribution of TLOSRs to reflux frequency vs acid exposure time were 65 vs 54% interprandially and 74 vs 53% after the meal. During the night, absence of basal LOS pressure accounted for 36% of reflux events representing 71% of acid exposure time. In conclusion, the duration of oesophageal acid exposure following a TLOSR is shorter than reflux during absent basal LOS pressure. TLOSRs are, the major contributor to oesophageal acid exposure during the day. At night, however, reflux during absent basal LOS pressure is the major contributor to acid exposure.     

Motor events underlying gastro-oesophageal reflux in ambulant patients with reflux oesophagitis

Abstract Information on the mechanism of gastro-oesophageal reflux in patients with reflux disease is limited largely to studies in resting recumbent subjects. Evidence exists that both posture and physical activity may influence reflux. The aim of this study was to investigate reflux mechanisms in ambulant patients with reflux oesophagitis. Concurrent ambulatory oesophageal manometry and pH monitoring were performed in 11 ambulant patients with erosive oesophagitis. Lower oesophageal sphincter (LOS) pressure was monitored with a perfused sleeve sensor. Recordings were made for 90 min before and 180 min after a meal. At set times patients sat in a chair or walked. LOS pressure was ≤2 mmHg at the time of reflux for 98% of reflux episodes. Transient LOS relaxation was the most common pattern overall and the predominant pattern in seven patients, whilst persistently absent basal LOS pressure was the most common pattern in four patients. The pattern of LOS pressure was not altered by the presence of hiatus hernia or by walking. Straining occurred at the onset of 31% of acid reflux episodes but often followed the development of an oesophageal common cavity. The occurrence of straining was not influenced by walking. In ambulant patients with reflux oesophagitis: (1) LOS pressure is almost always absent at the time of reflux, usually because of transient LOS relaxation, (2) persistently absent basal LOS pressure is an important mechanism of reflux in a few patients, (3) straining may help to induce acid reflux in a variable proportion of occasions and may in some instances be a response to gas reflux, and (4) walking does not influence the occurrence of reflux or its mechanisms.     

Effect of baclofen on oesophageal motility and transient lower oesophageal sphincter relaxations in GORD patients: a 48-h manometric study

Abstract  Little is known about prolonged effect of baclofen on oesophageal and lower oesophageal sphincter (LOS) motility. We aimed at investigating the oesophageal motility in gastro-oesophageal reflux disease (GORD) patients 24 h before and after the administration of multiple doses of baclofen. Twenty-one GORD patients underwent a 48-h manometry recording the swallows, the oesophageal and the LOS motility. During the second 24-h period, patients received baclofen 10 mg or placebo four times per day in a double-blind randomized fashion. Baclofen increased the LOS basal tone in comparison with baseline ( P  = 0.02), with a concomitant reduction in the number of transient LOS relaxations (TLOSRs) ( P  = 0.01). Moreover, baclofen induced a decrease of the swallows ( P  = 0.02) and of primary oesophageal body waves ( P  = 0.04) with no changes in the amplitude. Multiple doses of baclofen determine a reduction in the number of TLOSRs and an increase in the LOS tone throughout the 24 h. The concomitant decreased number of swallows and of primary peristalsis could depend on the well-known lower amount of reflux episodes induced by the drug. The potential therapeutic effect of baclofen could be expressed not only postprandially, but also in the fasting state when reflux episodes are present as well.     

Correlation between gastric pH and gastro-oesophageal reflux contents: ambulatory pH-impedance monitoring results

Gastro-oesophageal reflux events should be related to gastric contents. The goal of this study was to determine the relationship between gastric pH and the nature of reflux events. Ambulatory oesophageal pH-impedance and gastric pH monitoring was performed in 41 patients [29 off and 12 on proton pump inhibitor (PPI) therapy] and 12 controls. The mean gastric pH was measured within 2 min around the reflux episodes, 10 cm below the cardia. Acid reflux events occurred more frequently at gastric pH <4 (89%) than non-acid reflux events (63%, P < 0.0001). Acid reflux events extended more frequently 15 cm above the lower oesophageal sphincter (LOS; 34%) than non-acid reflux episodes (24%, P = 0.005). Gastric pH was significantly lower during interprandial reflux events than during postprandial ones in the three groups (P < 0.001). A positive correlation was found between gastric pH and the nadir oesophageal pH during reflux events in the three groups: this correlation was more significant in patients on PPI therapy. We conclude that most acid and non-acid reflux episodes occur at acid gastric pH, as measured 10 cm below the LOS. This measure does not appear a good predictor of the pH of reflux events.     

Effect of lateral positioning on gastroesophageal reflux (GER) and underlying mechanisms in GER disease (GERD) patients and healthy controls

Background Posture has been shown to influence the number of transient lower esophageal sphincter relaxation (TLESRs) and gastroesophageal reflux (GER), however, the physiology explaining the influence of right lateral position (RLP), and left lateral position (LLP) is not clear. The aim of this study was to determine the influence of RLP and LLP on TLESRs and GERD after a meal in GER disease (GERD) patients and healthy controls (HC) while monitoring gastric distension and emptying. Methods Ten GERD patients and 10 HC were studied for 90 min (30 min test meal infusion, 30 min postprandial in either RLP or LLP (randomly assigned) and 30 min in alternate position). The study was repeated on a separate day in reverse position order. TLESRs, GER, and gastric emptying rate were recorded using manometry, multichannel intraluminal impedance, and ¹³C‐octanoate breath tests. Gastric distension was visualized by five serial gastric volume scintigraphy scans during the first 30 min. Key Results Gastroesophageal reflux, (GER) disease patients had increased numbers of TLESRs in RLP compared to LLP in the first postprandial hour [5 (4–14) and 4.5 (2–6), respectively, P = 0.046] whereas the number of TLESRs was not different in RLP and LLP [4 (2–4) and 4 (3–6), respectively, P = 0.7] in HC. Numbers of GER increased similar to TLESRs in GERD patients. In GERD patients, gastric emptying reached peak ¹³CO₂ excretion faster and proximal gastric distension was more pronounced. Conclusions & Inferences In GERD patients, TLESRs, GER, distension of proximal stomach, and gastric emptying are increased in RLP compared to LLP. This effect is not seen in HC.     

Reproducibility of meal-induced transient lower oesophageal sphincter relaxations in patients with gastro-oesophageal reflux disease

AIM: To calculate the number of subjects required in trials investigating drugs reducing the number of transient lower oesophageal sphincter relaxations (TLOSRs), the inter- and intra-individual variability of TLOSRs were determined, using meal ingestion as a trigger of TLOSRs and reflux. METHODS: A total of 23 gastro-oesophageal reflux disease (GORD) patients with no to grade B oesophagitis and a hiatal hernia < or =3 cm underwent oesophageal manometry and pHmetry 1 h before and 3 h after ingestion of a solid meal on two separate days approximately 4 weeks apart. Reflux episodes and the underlying mechanisms and the number of TLOSRs were evaluated. RESULTS: The number of TLOSRs, reflux episodes and % time with pH < 4 after meal ingestion did not differ significantly between the two sessions. The intra-individual variation of TLOSRs in the 3 h postprandial period (24.4) was smaller compared with the inter-individual variation (47.5). Transient lower oesophageal sphincter relaxations were the predominant cause of reflux accounting for 61 +/- 7 and 70 +/- 5% of the reflux episodes in visits 1 and 2, respectively. CONCLUSIONS: These data for the first time provide information on the variability of TLOSRs and reflux evoked by meal ingestion, which is of crucial importance for the design and power calculations of future clinical studies evaluating the efficacy of new drugs targeting TLOSRs.     

Transient lower oesophageal sphincter relaxations play an insignificant role in gastro-oesophageal reflux to the proximal oesophagus.

Gastro-oesophageal reflux to the proximal oesophagus may cause atypical symptoms of gastro-oesophageal reflux disease (GORD). The motor abnormalities underlying reflux into the proximal oesophagus are still unclear. The aim of this study was to analyse the oesophageal motility during reflux into the proximal oesophagus in a group of healthy subjects and in patients with atypical symptoms of GORD. We concentrated particularly on lower oesophageal sphincter (LOS) activity and transient lower oesophageal sphincter relaxations (TLOSRs). Ten patients (7M, 3F, age 25-51 years) with mild oesophagitis (Savary-Miller grade I-II) and 10 healthy subjects (6M, 4F, age 23-54 years) underwent a 24-h dual pH-metric and manometric recording, using an electronic portable device. This recorded distal and proximal oesophageal pH values, oesophageal body and LOS motility. GORD patients had more distal and proximal reflux (DR and PR) compared with healthy controls (DR P < 0.001; PR P < 0.05). TLOSRs were the most frequent event during reflux into the distal oesophagus, whereas TLOSR frequency was much lower during reflux to the proximal oesophagus in GORD patients and in healthy controls (P < 0.05 and P < 0.01 vs. distal reflux, respectively). A significant relationship between TLOSRs and distal refluxes was present but no relationship with proximal reflux was detected. We conclude that TLOSRs are much less frequent during reflux to the proximal oesophagus than distal oesophageal reflux in patients with mild GORD suffering from atypical manifestations. The mechanism of acid reflux to the proximal oesophagus is unclear.     

Effect of the 5-HT1 agonist sumatriptan on oesophageal motor pattern in patients with ineffective oesophageal motility

The 5-HT1 agonist sumatriptan (SUM) elicits an increase in amplitude of oesophageal motor waves and of lower oesophageal sphincter (LOS) tone in healthy subjects. The aim of the study was to evaluate whether such an effect occurs also in patients with ineffective oesophageal motility (IOM). 16 patients (nine males and seven females, age range 34-55 years) with chest pain and mild to moderate dysphagia were studied; all had undergone previous cardiologic, radiologic and upper gastrointestinal endoscopic exams that were normal. An oesophageal manometry was performed using an electronic probe to record swallows, oesophageal, LOS and gastric motility. The patients whose motor pattern were compatible with IOM (>30% of motor waves with amplitude <30 mmHg and/or non-transmitted) received SUM or placebo 6 mg s.c., injected in the morning and in the afternoon in a random order. The data analysis was limited to 1 h before and 1 h after the drug injections. Ten out of the 16 patients showed an IOM motor pattern. The administration of SUM caused a significant increase in the number of swallows (SUM 99.5 +/- 15.4 vs 78.6 +/- 16.1 basal, P = 0.03) and of primary oesophageal motor waves (SUM 89.6 +/- 13.4 vs 67.2 +/- 12.9 basal, P = 0.04) with no significant changes in the percentage of swallows associated with propagation. Placebo was not associated with increase in the number of swallows (80.3 +/- 14.6, P = 0.9) or of primary oesophageal motor waves (70.1 +/- 12.3, P = 0.7). The amplitude and the percentage of propagated oesophageal motor waves as well as the mean basal LOS tone were unaltered by SUM. There was no change in the symptoms reported after SUM. Although effective in healthy subjects, SUM 6 mg s.c. improves only the numbers but not the amplitude or propagation of oesophageal motility of patients with IOM. The 5-HT1 pathway and its acute stimulation seem to play only a minor role in the pathogenesis of such a disease.     

Monitoring the lower oesophageal sphincter: sphinctometer or sleeve?

Two methods have been used to study lower oesophageal sphincter (LOS) function in gastro-oesophageal reflux disease: the sleeve sensor and the sphinctometer. Our aim was to directly compare the sleeve and sphinctometer in vivo. Ten asymptomatic volunteers were intubated with a perfused assembly incorporating a sleeve sensor, a solid-state assembly incorporating a sphinctometer and a pH probe. LOS function was recorded pre- and post-prandially. During basal periods sleeve and sphinctometer readings correlated well both within and between subjects (r2 = 0.89 (P < 0.0001)). However, the sphinctometer relaxed less during swallows (median 42 (interquartile range 27-55)% vs 73 (62-81)% (P < 0.001)), transient LOS relaxations (TLOSR) (50 (40-70)% vs 94 (88-100)% (P < 0.001)) and reflux episodes (67 (59-75)% vs 97 (91-100)% (P = 0.02)). Using criteria derived from 10 dry swallows, the expected relaxation of the sphinctometer during TLOSR was defined. The sphinctometer had an overall sensitivity ranging from 43 to 71% for the detection of TLOSR with 11-22 false positive relaxations, depending on the criteria employed. Sensitivity was particularly poor in those with low basal LOS pressure. The sphinctometer has a lower capacity to register LOS relaxations than the sleeve sensor, which limits its value in studying the pathophysiology of reflux disease.     

Impedance monitoring shows that posture and a meal influence gastro‐oesophageal reflux composition and frequency1

Abstract Impedance monitoring determines reflux composition as liquid and/or gas, and we assess with impedance the effect of posture and a meal on reflux composition. Twenty‐nine gastro‐oesophageal reflux disease (GORD) patients and 10 normal volunteers underwent simultaneous impedance, manometry and pH for three 40‐min periods, each 20‐min upright, 10‐min left side and 10‐min right side. One period was fasting, and two postprandial. We found that reflux event composition on the right side was liquid‐only near exclusively (93%). In contrast, 85% of reflux on the left side and 74% upright was gas‐only or liquid and gas (P < 0.001). More gas‐only reflux occurred fasting (80%) than postprandial (P < 0.01). Reflux composition was similar in the study groups and two postprandial periods (P > 0.25). After confirming gas reflux suppression on the right side, a pilot study assessed gastric anatomy as a cause. Five achalasia patients had fluid injected into the stomach at endoscopy, and the EG junction was submerged below liquid‐only on the right side. We conclude that reflux is nearly always liquid‐only on the right side where the EG junction may be below fluid. Reflux fasting is usually gas‐only. Different posture and fasting times may (i) explain variations in acid exposure during pH monitoring and (ii) promote or prevent GORD symptoms.     

Effect of proximal gastric volume on hiatal hernia

Background Spatial separation of the diaphragm and the lower esophageal sphincter (LES) occurs frequently and intermittently in patients with a sliding hiatus hernia and favors gastro‐esophageal reflux. This can be studied with high‐resolution manometry. Although fundic accommodation is associated with a lower basal LES pressure, its effect on esophagogastric junction configuration and hiatal hernia is unknown. Therefore, the aim of this study was to investigate the relationship between proximal gastric volume, the presence of a hiatal hernia profile and acid reflux. Methods Twenty gastro‐esophageal reflux disease (GERD) patients were studied and compared to 20 healthy controls. High‐resolution manometry and pH recording were performed for 1 h before and 2 h following meal ingestion (500 mL per 300 kcal). Volume of the proximal stomach was assessed with three‐dimensional ultrasonography before and every 15 min after meal ingestion. Key Results During fasting, the hernia profile [2 separate high‐pressure zones (HPZs) at manometry] was present for 31.9 ± 4.9 min h^?1 (53.2%) in GERD patients, and 8.7 ± 3.3 min h^?1 (14.5%) in controls (P < 0.001). In GERD patients, the presence of hernia profile decreased during the first postprandial hour to 15.9 ± 4.2 min h^?1, 26.5%, P < 0.01 whilst this phenomenon was not observed in controls. The rate of transition between the two profiles was 5.7 ± 1.1 per hour in GERD patients and 2.5 ± 1.0 per hour in controls (P < 0.001). The pre and postprandial acid reflux rate in GERD patients during the hernia profile (6.4 ± 1.1 per hour and 18.4 ± 4.3 per hour respectively) was significantly higher than during reduced hernia (2.1 ± 0.6 per hour; P < 0.05 and 3.8 ± 0.9 per hour; P < 0.05). A similar difference was found in controls. Furthermore, an inverse correlation was found between fundic volume and the time the hernia profile was present (r = ?0.45; P < 0.05) in GERD patients, but not in controls. Conclusions & Inferences (i) In GERD patients a postprandial increase in proximal gastric volume is accompanied by a decrease in hernia prevalence, which can be explained by a reduction of the intra‐thoracic part of the stomach. (ii) A temporal hernia profile also occurs in healthy subjects. (iii) During the hernia profile, acid reflux is more prevalent, especially after meal ingestion.     

Postprandial gastric antral contractions in patients with gastro-oesophageal reflux disease: a scintigraphic study

Abstract  Disturbed gastric contractility has been found in manometric studies in patients with gastro-oesophageal reflux disease (GORD), but the pathophysiological role of this abnormality is unclear. We aimed at assessing postprandial gastric antral contractions and its relationships with gastric emptying and gastro-oesophageal reflux in GORD patients. Fasted GORD patients ( n  = 13) and healthy volunteers ( n  = 13) ingested a liquid meal labelled with 72 MBq of ^99mTechnetium-phytate. Gastric images were acquired every 10 min for 2 h, for measuring gastric emptying half time. Dynamic antral scintigraphy (one frame per second), performed for 4 min at 30-min intervals, allowed estimation of both mean dominant frequency and amplitude of antral contractions. In GORD patients ( n  = 10), acidic reflux episodes occurring 2 h after the ingestion of the same test meal were determined by ambulatory 24-h oesophageal pH monitoring. Gastric emptying was similar in GORD patients and controls (median; range: 82 min; 58–126 vs 80 min; 44–122 min; P  = 0.38). Frequency of antral contractions was also similar in both groups (3.1 cpm; 2.8–3.6 vs 3.2 cpm; 2.4–3.8 cpm; P  = 0.15). In GORD patients, amplitude of antral contractions was significantly higher than in controls (32.7%; 17–44% vs 23.3%; 16–43%; P  = 0.01), and correlated positively with gastric emptying time ( R _s = 0.58; P  = 0.03) and inversely with the number of reflux episodes ( R _s = −0.68; P  = 0.02). Increased amplitude of postprandial gastric antral contractions in GORD may comprise a compensatory mechanism against delayed gastric emptying and a defensive factor against acidic gastro-oesophageal reflux.     

Distinct patterns of oesophageal shortening during primary peristalsis, secondary peristalsis and transient lower oesophageal sphincter relaxation

This study characterized oesophageal shortening during secondary peristalsis and transient lower oesophageal sphincter relaxation (TLOSR) in an attempt to determine its contribution to the opening mechanism. Eight healthy subjects (four males, 26 +/- 1 years) had metal clips affixed at 0, +3, and +8 cm relative to the squamocolumnar junction (SCJ), defining two distal oesophageal segments. Axial clip movement was assessed with concurrent videofluoroscopy and manometry during primary peristalsis, secondary peristalsis and TLOSR. Clip-defined oesophageal segment length change was measured at 0.5-s intervals. The magnitude of the most distal segment shortening was least with TLOSR, greatest with primary peristalsis and intermediate with secondary peristalsis. Conversely, maximal overall oesophageal shortening during TLOSR, evidenced by SCJ movement, was similar to that during primary peristalsis. In 3/12 TLOSRs, the moment of LOS opening and gas reflux was optimally imaged; SCJ excursion was 0.3 +/- 0.1 cm prior to LOS opening and 1.4 +/- 0.7 cm immediately after gas reflux. The segmental pattern of oesophageal shortening was distinct during primary peristalsis, secondary peristalsis and TLOSR. During TLOSR, significant elevation of the SCJ occurred only after LOS opening, suggesting that this was a consequence of oesophageal distension induced by gas reflux rather than a component of the opening mechanism.     

Upper sphincter function during transient lower oesophageal sphincter relaxation (tLOSR); it is mainly about microburps

Transient lower oesophageal sphincter relaxations (tLOSRs) are both a dominant mechanism of reflux and an element of the belch reflex. This study aimed to analyse the interplay between reflux and upper oesophageal sphincter (UOS) activity during meal-induced tLOSRs. Fifteen normal subjects were studied with a solid-state high-resolution manometry assembly positioned to record from the hypopharynx to the stomach and a catheter pH electrode 5 cm above the LOS. Subjects ate a 1000-calorie high-fat meal and were monitored for 120 min in a sitting posture. The relationship among tLOSRs, common cavities, pressure changes within the oesophagus and UOS contractile activity were analysed. A total of 218 tLOSRs occurred among the 15 subjects. The majority (79%) were coupled with UOS relaxation and 84% (145/173) of these occurred in association with a common cavity. Upper oesophageal sphincter relaxation was usually preceded by a pressure change in the oesophagus; however, some relaxations (16%) occurred without a discernable increase in pressure or before the pressure increase began. Acid reflux did not appear to play a role in determining UOS response to tLOSRs. The majority of post-prandial tLOSRs were associated with brief periods of UOS relaxation, likely permissive of gas venting (microburps). Intraoesophageal pressure changes likely modulate this UOS response; however, an anticipatory characteristic was evident in some subjects. Whether or not GORD patients with extra-oesophageal symptoms exhibit an exaggeration of the UOS relaxation response during reflux is yet to be determined.     

Effects of position on oesophageal function: studies using combined manometry and multichannel intraluminal impedance

Multichannel intraluminal impedance (MII) allows assessment of intraoesophageal bolus transit. In the supine position, bolus transit is produced almost exclusively by peristaltic contractions; in the upright position, gravity also contributes to bolus transit. MII and peristaltic pressures were measured in four positions (0, 30, 60 and 90 degrees ) using ten swallows (5 cc each) of both water and viscous liquid with body position determined by random choice. Tracings were analysed for total bolus transit time: time interval between bolus entry at 20 cm above and bolus exit at 5 cm above the lower oesophageal sphincter (LOS) and contraction amplitudes at 5 and 10 cm above the LOS. Statistical comparison of mean values of all four body positions was done using anova and Bonnferoni post-test. Ten normal subjects (five females and five males, age 24-45 years) completed the study. At each body position, liquid material transited faster (P < 0.001) than viscous material. Both liquid and viscous materials transited at lower inclinations (0 and 30 degrees ) significantly slower than at higher inclinations (60 and 90 degrees ). There was an almost perfect inverse linear correlation between angle of inclination and bolus transit time for both liquid (r = -0.99) and viscous (r = -1.00) boluses (Spearman correlation r > 0.99 and P < 0.02 for both substances). Contraction amplitudes for liquid vs viscous material were not significantly different at a given degree of inclination. Mean distal oesophageal amplitude declined with increasing inclination. Combined MII-OM identifies and quantifies the effects of gravity on the dichotomy between specific pressures measured by OM and function assessed as transit measured by MII.     

Mechanisms of gastro-oesophageal reflux in the ferret

Transient lower oesophageal sphincter (LOS) relaxation is the major mechanism of gastro-oesophageal reflux in humans – an event unassociated with swallowing. Mechanisms involved in triggering transient LOS relaxation are poorly understood, and their further study requires a small animal model. In this study we aimed to establish methods for prolonged ambulant oesophageal manometry in ferrets, and to determine motor events associated with reflux episodes and their triggering by different gastric nutrient loads. Forty-two studies were performed on nine ferrets with chronic cervical oesophagostomies, through which a manometric assembly was introduced and secured to a collar, which incorporated a microphone for detection of swallows. The assembly included a gastric feeding channel, one gastric and four oesophageal manometric sideholes, a 2.5-cm-long LOS sleeve sensor, and an oesophageal pH electrode. Intragastric infusions were given over 2 min, the first after a 30-min control recording period, and in 29/42 studies, a second infusion was given 60 min later. Infusions were either 25 mL 10% dextrose solution, pH 3.5 (22 studies), 25 mL triglyceride emulsion (Intralipid) pH 3.5 (11 studies), or 25 mL air (nine studies). Episodes of oesophageal acidification were absent before gastric infusions. After infusion, 2.1 ± 0.2 episodes occurred over the first 30 min. After glucose infusion, 15/18 acidification episodes (83%) occurred during transient LOS relaxation, and 3/18 (17%) occurred after gradual (< 1 mmHg sec⁻¹) downward drifts in basal LOSP to < 2 mmHg. After lipid infusion two acidification episodes occurred, both during transient LOS relaxation. Mean duration of transient LOS relaxation was 8.0 ± 0.4 sec. All infusions increased occurrence of transient LOS relaxation to a similar extent, each of which ended with primary peristalsis. We conclude that gastric infusion of glucose, lipid and gas are all effective in provoking gastro-oesophageal reflux in ferrets. Reflux occurs through similar mechanisms to those seen in humans, i.e. increased triggering of transient LOS relaxation. The conscious ferret is therefore an appropriate model for future studies of manipulation of mechanisms giving rise to gastro-oesophageal reflux.     

Prolonged recording of oesophageal and lower oesophageal sphincter pressure using a portable water-perfused manometric system

The aim of our study was to investigate the recording fidelity of a water-perfused micromanometric catheter with incorporated sleeve combined with a newly developed portable water-perfused manometric system for pharyngeal, oesophageal and lower oesophageal sphincter (LOS) pressure recording. The system's performance was assessed in prolonged recordings in ambulant gastro-oesophageal reflux disease (GORD) patients. Eighty 24-h studies in GORD patients, carried out with the perfused portable manometric system, were evaluated. Twelve of these recordings were analysed in detail in order to compare oesophageal and LOS motor patterns with those described previously. Paired 2-h manometric recordings of the pharynx, oesophagus, LOS and stomach, using the new system and a conventional perfused stationary manometric system, were performed in eight healthy subjects. With the portable manometric system oesophageal contractions, transient LOS relaxations, swallow-associated prolonged LOS relaxations and LOS pressures were recorded with equal fidelity to the conventional manometric system. Recordings obtained with the portable system showed meal-related and diurnal variations in oesophageal and LOS variables that were similar to these found in studies using conventional equipment. The new manometric system, consisting of a perfused micromanometric catheter with incorporated sleeve and a portable perfusion system, enables prolonged studies on oesophageal and LOS motor patterns in ambulant subjects.     

Rumination or belching–regurgitation? Differential diagnosis using oesophageal impedance–manometry

Background Rumination is an eating disorder clinically suspected in the presence of chronic regurgitation of recently ingested food with subsequent re‐mastication and swallowing. Oesophageal manometry is currently used to confirm the diagnosis, however, it is difficult to distinguish rumination from postprandial belching‐regurgitation, being the manometric pattern identical in both situations. Oesophageal impedance allows recognition between liquid and gas gastro‐oesophageal reflux. Our aims were (i) to improve diagnosis of rumination using combined impedance–manometry (ii) to assess the gastro‐oesophageal pressure‐flow pattern in rumination events. Methods Sixteen patients with clinically suspected rumination underwent impedance–manometry monitoring for 1 h after a solid liquid meal. Manometry was first analysed blindly to the impedance pattern. All events marked by the patients and straining episodes were identified. After the manometric analysis, impedance tracings were unblinded and each straining episode was analysed for presence of liquid and/or gas oesophageal retrograde flow. Only rumination events were included for additional evaluation. Key results Postprandial manometry showed a pattern compatible with rumination in 12/16 patients. In total, impedance–manometry confirmed the clinical diagnosis of rumination in eight of the 16 patients with clinical suspicion of rumination. In 102 clearly identified rumination events, the onset of gastric strain (manometry) occurred before the onset of oesophageal liquid retroflow (impedance) in 58% of cases or simultaneously in 37% of cases. In most cases (86%), oesophageal retrograde flow started after an initial increase in abdominal pressure but before the peak gastric strain pressure. Conclusions & Inferences Postprandial impedance–manometry monitoring improves diagnosis of rumination because it allows distinction between rumination and postprandial belching and regurgitation. During rumination, oesophageal liquid retrograde flow is first driven by an early small rise in intragastric pressure preceding the peak pressure observed during straining.     

Effect of an acute intraluminal administration of capsaicin on oesophageal motor pattern in GORD patients with ineffective oesophageal motility

Ineffective oesophageal motility (IOM) is a functional disorder affecting about 50% of gastro-oesophageal reflux disease (GORD) patients. This disease in a severe form limits the clearing ability of the oesophagus and is considered one of the predictive factors for poorer GORD resolution. Capsaicin, the active compound of red pepper, exerts a prokinetic effect on oesophageal motility in healthy subjects by increasing the amplitude of body waves, even if no evidence exists on its possible role in situations of reduced motility. The aim of the study was to evaluate the effect of an acute administration of capsaicin on the oesophageal motor pattern in a group of GORD patients affected by severe IOM. Twelve GORD patients with severe IOM received an intra-oesophageal administration of 2 mL of a red pepper-olive oil mixture and 2 mL of olive oil alone serving as a control during a stationary manometry. The motor patterns of the oesophageal body and lower oesophageal sphincter (LOS) were analysed at baseline and after the infusion of the two stimuli. The administration of capsaicin induced a significant improvement in oesophageal body contractility when compared with baseline. The velocity of propagation of waves and the LOS basal tone remained unchanged. The motor pattern was unaltered by the administration of olive oil alone. An acute administration of capsaicin seems to improve the motor performance of the oesophageal body in patients with ineffective motility. Whether this could represent the basis for further therapeutic approaches of GORD patients needs further study.     

Effect of sildenafil, a phosphodiesterase-5 inhibitor, on oesophageal peristalsis and lower oesophageal sphincter function in cats.

The propagation of oesophageal peristaltic contractions and lower oesophageal sphincter (LOS) relaxation depends on neural release of nitric oxide (NO) which acts to increase intracellular cGMP. Sildenafil, a phosphodiesterase-5 inhibitor that increases cGMP, reduces basal LOS pressure in patients with achalasia. We investigated the effect of sildenafil on the propagation of oesophageal contractions and LOS relaxation in the cat. Oesophageal manometry was performed in five cats under light sedation. Peristaltic contractions were monitored at 1, 2, 3, 4 and 8 cm proximal to the LOS, at the LOS using a Dent sleeve, and at 3 cm distal to the upper oesophageal sphincter. Swallow-induced oesophageal contractions and LOS relaxation were recorded during 30 min before and 30 min after intravenous administration of sildenafil. Sildenafil reduced the amplitude of oesophageal contractions only in the smooth muscle oesophagus. The latency from swallow to distal oesophageal contractions was significantly delayed. LOS pressure was significantly reduced but the relaxation nadir was not modified by sildenafil. Sildenafil has profound effects on oesophageal motility: it modifies propagation and amplitude of oesophageal contractions and reduces LOS pressure. Slowing down the propagation of contractions in the transitional zone between the striated and smooth muscle can be a useful tool in patients with segmental aperistalsis or intermittent simultaneous contractions, while the effect on the LOS can benefit patients with achalasia.