Effect of an o-raffinose cross-linked haemoglobin product on oesophageal and lower oesophageal sphincter motor function

The present experiments evaluate the effects on oesophageal motility of an o-raffinose cross-linked haemoglobin-based oxygen carrier (HBOC) purified from outdated donated human blood cells (HemolinkTM), with attention to dose-response (0.6-2.4 g kg-1), oxygenation status and low molecular weight components (4.4-36.4% 64 kDa or less). In ketamine-anaesthetized cats, lower oesophageal sphincter (LES) function and oesophageal peristalsis were monitored 0.5 h before, during and up to 3.5 h after HBOC infusion, and in some cats at 24 h. (1) All products significantly inhibited LES relaxation and increased peristaltic velocity in the distal smooth muscle oesophagus, without consistently altering resting LES pressure. (2) Effects on peristaltic velocity reached a maximum at the smallest dose, whereas the effects on LES relaxation had a maximum effect at 1.2 g kg-1. (3) Effects were not significantly altered by the haemoglobin oxygenation status or presence of low molecular weight components. (4) Repetitive oesophageal contractions occurred. In the cat, an o-raffinose cross-linked human haemoglobin product produces changes in oesophageal body and LES function, which are independent of the HBOC oxygenation status and composition of the low molecular weight components tested. Changes may persist for at least 24 h. These motility changes are likely due to scavenging of nitric oxide by the haemoglobin.     

Sildenafil relieves symptoms and normalizes motility in patients with oesophageal spasm: a report of two cases

Oesophageal spasm presents with dysphagia and chest pain. Current treatments are limited by poor efficacy and side effects. Studies in health and oesophageal dysmotility show that sildenafil reduces peristaltic pressure and velocity; however the clinical efficacy and tolerability in symptomatic oesophageal spasm remains uncertain. We provided open-label sildenafil treatment to two patients with severe, treatment resistant symptoms associated with oesophageal spasm. The effects of sildenafil on oesophageal function and symptoms were documented by high resolution manometry (HRM). Patients were followed up to assess the efficacy of maintenance treatment with sildenafil b.i.d. HRM revealed focal and diffuse spasm in the smooth muscle oesophagus that were associated with symptoms in both cases, especially on swallowing solids. Lower oesophageal sphincter function was normal. A therapeutic trial of 25-50 mg sildenafil suppressed oesophageal contraction almost completely for water swallows; however effective, coordinated peristalsis returned with reduced frequency of spasm for solid swallows. Dysphagia and chest pain resolved during the therapeutic trial and efficacy was maintained on maintenance treatment with 25-50 mg sildenafil b.i.d. without troublesome side effects. This report shows that sildenafil can improve oesophageal function and relieve dysphagia and chest pain in patients with oesophageal spasm in whom other treatments have failed.     

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.     

Segmental characteristics of oesophageal peristalsis in paediatric patients.

High-resolution manometry (HRM) in adults identifies a sequential chain of pressure segments that together form normal oesophageal peristalsis. HRM was performed in 40 neonates, infants/toddlers and children (age 1 day-14 years) to see if a similar segmental pattern could be identified in paediatric subjects. A chain of three pressure segments was found with inter-segmental troughs at 27.4 +/- 1.1%, 62.6 +/- 1.3% and 94.9 +/- 0.8% oesophageal length. The first and second pressure troughs were similarly distributed along the oesophagus across age groups; the third was 7.6-8.9% oesophageal length further from the lower oesophageal sphincter in neonates (P < 0.05 compared with other age groups). There were no significant differences in trough locations between subjects with or without oesophageal disease, controlling for age. Consistent presence of all three segments was less common in neonates, primarily because of fewer swallows demonstrating the first (proximal) and third (distal) segments compared with children. HRM in paediatric patients demonstrates, from neonates to children, the distinctive chain of pressure events that also characterizes oesophageal peristalsis in adults. The segmental character to oesophageal peristalsis should be taken into consideration in manometric investigation of all age groups - for example, in testing pharmacological responses and evaluating clearance mechanisms.     

Effect of endotoxin on opossum oesophageal motor function

Endotoxin induces nitric oxide (NO*) synthase and alters gastrointestinal functions. We explored the effect of lipopolysaccharide (LPS) on oesophageal motor function at 6, 12, 24, and 48 h. The effects of inhibiting inducible NO* synthase (iNOS) were studied 12 h after administration of LPS with/without aminoguanidine (AG). Oesophageal manometry was performed and tissue bath studies were performed with muscle strips from the oesophagus and lower oesophageal sphincter (LOS). Plasma nitrite/nitrate concentrations were determined. The amplitudes of peristaltic pressure waves, resting LOS pressure and the percentage LOS relaxations were diminished by LPS. AG attenuated the decrease in amplitude of oesophageal pressure waves, LOS pressure, and percentage relaxation of LOS brought about by LPS. LPS decreased electrical field stimulation (EFS)-induced relaxation of LOS muscle. AG attenuated this decrease in LOS relaxation. The off-response of transverse oesophageal muscle strips was decreased, and AG antagonized this effect. Plasma concentrations of nitrite/nitrate were increased. The increase in plasma nitrite/nitrate was attenuated by AG. These studies support the hypothesis that endotoxin modulates oesophageal motor function by increasing NO production and suggest that this results from the induction of iNOS.     

The effect of sildenafil on oesophageal motor function in healthy subjects and patients with nutcracker oesophagus

Type 5 phosphodiesterase terminates the action of nitric oxide (NO) induced 3',5'-cyclic monophosphate (cGMP). Sildenafil inhibits this phosphodiesterase, increases cellular cGMP concentrations and enhances NO-induced smooth muscle relaxation. We investigated the effect of sildenafil on the oesophageal motor function of healthy subjects and patients with nutcracker oesophagus. Eight healthy volunteers and nine patients with nutcracker oesophagus participated in this study. The participants underwent oesophageal manometries on two separate days after either 20 mL of distilled water or 0.8 mg kg-1 sildenafil dissolved in 20 mL of water was infused into the stomach. Lower oesophageal sphincter (LOS) resting pressure, the duration of LOS relaxation and the amplitudes of oesophageal pressure waves were examined before, and 7.5, 15, 30 and 60 min after either placebo or sildenafil. In both healthy subjects and patients with nutcracker oesophagus, sildenafil decreased resting LOS pressure and the amplitude of peristaltic pressure waves at 3, 8 and 13 cm above LOS. Sildenafil also prolonged the duration of LOS relaxation. It had no effect on the velocity of peristalsis or the amplitude of peristaltic pressure waves 18 cm above LOS. Sildenafil may be considered as an alternative treatment in nutcracker oesophagus although there are several limitations to be overcome.     

Interstitial cells of Cajal and neuromuscular transmission in the rat lower oesophageal sphincter

The distribution of interstitial cells of Cajal (ICC) and neurotransmission were investigated in lower oesophageal sphincter (LES) circular muscle strips from Sprague-Dawley (SD) rats, Ws/Ws mutant rats and their wild-type (+/+) siblings. Intramuscular c-Kit-positive cells, confirmed to be ICC-IM by electron microscopy, were observed throughout both muscle layers from SD and +/+ rats. In contrast, c-Kit-positive, ultrastructurally typical ICC-IM were absent in Ws/Ws. LES strips from Ws/Ws rats showed increased spontaneous contractile activity. Strips from SD and +/+ rats, responded to electrical neuronal stimulation with a relaxation that was in part L-NNA and in part apamin sensitive, followed by a contraction which was decreased by atropine. In Ws/Ws rats, similar to +/+ rats, neurally mediated relaxation was L-NNA and apamin sensitive and the contraction was decreased by atropine. We conclude that in the rat LES, relaxation is mediated by NO and an apamin-sensitive mediator, and contraction primarily by acetylcholine. Despite the absence of c-Kit-positive ICC, nerve-muscle interaction can be accomplished likely by diffusion of neurotransmitters to the smooth muscle cells. The lack of c-Kit-positive ICC is related to an increase in the basal tone and spontaneous contractile activity. The presence of fibroblast-like ICC in Ws/Ws rats might represent immature ICC whose possible functions need further investigation.     

Activation of non-adrenergic non-cholinergic inhibitory pathways by endogenous and exogenous tachykinins in the ferret lower oesophageal sphincter

Repeated oesophageal acidification causes lower oesophageal sphincter (LOS) relaxation in the anaesthetized ferret which is mediated by a peripheral neurokinin (NK-1) receptor mechanism. Our aim in this study was to characterize neural pathways in the LOS activated by capsaicin and tachykinin receptor agonists in vitro. Circular muscle strips of LOS (two per animal) from a total of 24 ferrets were maintained in organ baths. Electrical field stimulation (EFS, 50 V, 5–50 Hz) caused frequency-dependent LOS relaxation which was abolished by tetrodotoxin (TTX; 10⁻⁶ M : P < 0.001) and reduced by N^G-nitro-L -arginine (L-NNA; 10⁻⁴ M : P < 0.01). Substance P and [Sar⁹, Met (O₂)¹¹]-substance P (selective NK-1 agonist) caused dose-dependent relaxation, while the NK-2 receptor agonist [β-Ala⁸]-NKA 4-10 evoked excitation. Capsaicin (10⁻⁶ M ) caused relaxation and desensitization that was overcome by long recovery periods and substance P dosing (10⁻⁸ M ). After pretreatment with the NK-1 receptor antagonist CP 99994 (10⁻⁷ M ), substance P (10⁻⁸ M ; P < 0.001) and capsaicin (10⁻⁶ M : P < 0.01)-induced relaxations were reduced. In the presence of TTX (10⁻⁶ M ), excitation resulted in response to substance P (10⁻⁸ M ; P < 0.05) and [Sar⁹, Met (O₂)¹¹]-substance P (10⁻⁸ M ; P < 0.001), while the response to [β-Ala⁸]-NKA 4-10 (10⁻⁷ M ) was unaffected. In the presence of L-NNA (10⁻⁴ M ), substance P and [Sar⁹, Met (O₂)¹¹]-substance P-induced relaxations were reduced (10⁻⁸ M ; P < 0.01), while the response to [β-Ala⁸]-NKA 4-10 (10⁻⁷ M ) was unaffected. These results show that functional coupling between capsaicin-sensitive sensory neurones and NANC inhibitory neural pathways occurs via NK-1 receptors in the ferret LOS. NK-2 (and some NK-1) receptors activate non-neural excitatory mechanisms. Substance P and NK-1 receptors coupli ng sensory and NANC inhibitory neurones may be important in the reflex control of LOS motility.     

An experimental model for the study of transient lower oesophageal sphincter relaxation and motor function of the proximal stomach in humans

A simple and reliable experimental model would be useful in human research on new drugs which target transient lower oesophageal sphincter (LOS) relaxation. The aim was to investigate the effect of repeated distensions on the rate of transient LOS relaxation, LOS pressure and motor function of the proximal stomach. Twelve healthy subjects were studied with a multilumen manometric assembly incorporating a sleeve sensor for the LOS and a bag positioned in the proximal stomach and connected to a barostat. Intrabag volume was set at 75% of the threshold for gastric discomfort and maintained for two 30-min distension periods separated by a 45-min washout with the bag deflated. The studies lasted 145 +/- 2 min. The rate of transient LOS relaxations was similar during the two distensions, 3.5;2-4 vs 3;2.5-4 (median;interquartile range) and so was LOS pressure. Baseline intrabag pressure, as a measure of gastric tone, and the number of pressure waves, as a measure of phasic contractions, were also similar, 11.3;9.3-12.3 mmHg vs 10.8;9.3-12.5 mmHg and 16;13-28 mmHg vs 19;15-29 mmHg, respectively. Our model allows to perform 1-day studies which can assess two experimental conditions on transient LOS relaxations and motor function of the proximal stomach within an acceptable time span.     

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.     

Effects of wine on lower oesophageal sphincter pressure and oesophageal pH*

Abstract Eleven volunteers received 300 ml white wine, an ethanol solution and tap water to compare the effects of these beverages on lower oesophageal sphincter pressure and gastro-oesophageal reflux. A continuous measurement of sphincter pressure and oesophageal pH was performed one hour before and after ingestion. A significant increase in fraction of time pH<4 (P < 0.01 vs ethanol, P < 0.001 vs water) coincident with a significant decrease in sphincter pressure (P < 0.01) was observed after the intake of wine, The duration of transient sphincter relaxations (P < 0.05) as well as the duration of reflux episodes (P < 0.001) were significantly prolonged, its frequencies were not significantly enhanced. Reflux occurred almost exclusively during complete sphincter relaxations after the intake of ethanol and water, whereas an increase in ‘stress reflux’ and the occurrence of ‘free reflux’ was observed after ingestion of wine (P < 0.001). It is concluded that this change in reflux pattern is related to the depressive effect of wine on lower oesophageal sphincter pressure. Pure ethanol is not responsible for the effects of wine.     

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.     

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 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.     

Neural regulation of tone in the oesophageal body: in vivo barostat assessment of volume–pressure relationships in the feline oesophagus

Recent combined manometric-barostat studies demonstrated that the oesophageal body exhibits both peristaltic contractions and tone. This study further characterized the neural modulation of tone in the feline oesophageal body. Simultaneous oesophageal barostat and manometry were performed in 20 adult cats under ketamine sedation. Oesophageal tone and peristalsis were assessed in the distal smooth muscle oesophagus. Cholinergic modulation was studied using neostigmine, erythromycin, atropine and vagotomy. Nitrergic regulation was assessed using sildenafil to increase cellular cyclic guanosine monophosphate and the nitric oxide synthase blocker Nomega-nitro-l-arginine (l-NNA). The presence of a tonic contractile activity in the distal oesophageal body was confirmed. Peristaltic contractions proceeded along the oesophageal body over the background tonic contraction. Neostigmine and erythromycin enhanced (20-30%) whereas bilateral vagotomy and atropine strongly decreased oesophageal tone (50-60%). However, l-NNA increased (40%) and sildenafil decreased oesophageal tone (30%). Therefore, tonic contractile activity in the oesophageal body is mainly caused by a continuous cholinergic excitatory input. A nitric oxide inhibitory mechanism may have a complementary role in the regulation of oesophageal tone.     

Comparison of two techniques for lower oesophageal sphincter manometry: sleeve and sphinctometer

We have compared the sphinctometer with the water-perfused sleeve (gold standard) for measurement of lower oesophageal sphincter (LOS) characteristics by simultaneous recording. LOS pressure and transient LOS relaxations (TLOSR) measured by sleeve and sphinctometer in 11 healthy volunteers showed identical patterns. However, output of the sphinctometer was significantly (P < 0.01) lower than output of the sleeve. A total of 249 TLOSR were recorded. Of these, 176 TLOSR were identified by both sleeve and sphinctometer, 50 TLOSR were identified by sleeve alone and 23 TLOSR by sphinctometer alone. Due to the lower pressure output of the sphinctometer, 29 LOS relaxations did not reach criteria to qualify as TLOSRs. When TLOSR criteria were adjusted for sphinctometer pressure measurements, the number of TLOSRs identified by both sleeve and sphinctometer increased from 176 to 205. In conclusion, in healthy volunteers the sphinctometer registers TLOSR with results comparable with sleeve recording. However at low LOS pressures, the number of TLOSR is underscored by the sphinctometer.     

Release of nitric oxide in the central nervous system mediates tonic and phasic contraction of the cat lower oesophageal sphincter

Nitric oxide (NO) in the brainstem is implicated in the control of swallowing and oesophageal peristalsis. This study examines the role of brainstem NO in the maintenance of lower oesophageal sphincter (LOS) tone, relaxation and contraction. In urethane-anaesthetized cats, oesophageal peristalsis and sphincter pressures were continuously monitored. Drugs were administered into the fourth ventricle. Oesophageal peristalsis and sphincter relaxation and contraction were induced by superior laryngeal nerve stimulation or intra-oesophageal balloon distention. Basal sphincter pressure was significantly reduced after the i.c.v. administration of the nitric oxide synthase (NOS) inhibitor, l-Ng-monomethyl arginine. The inhibitor's d-isomer had no significant effect on basal sphincter pressure, while l-arginine partially reversed the effect. The NOS inhibitor had no effect on sphincter relaxation, whereas the contraction of the sphincter following relaxation was significantly inhibited. Central nitric oxide synthase inhibition reduces basal LOS tone and contraction amplitude but has no effect on swallow or balloon distention induced sphincter relaxation. Therefore, central release of NO acts in the pathway to stimulate dorsal motor nucleus of the vagus neurones projecting to excitatory neurones in the sphincter. Inhibition of nitric oxide synthase in the CNS does not prevent relaxation of the LOS, suggesting that other pathways that do not utilize NO are important in the induction of LOS relaxation.     

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.     

Impact of nadir lower oesophageal sphincter pressure on bolus clearance assessed by combined manometry and multi-channel intra-luminal impedance measurement

Abstract  This study aimed to assess the relationship between nadir lower oesophageal sphincter pressure (LOSP) and wave amplitude (WA) in oesophageal bolus clearance. Concurrent oesophageal manometry and impedance were performed in 146 subjects [41 healthy, 24 non-obstructive dysphagia (NOD) and 81 gastro-oesophageal reflux (GOR)]. Patients with achalasia and diffuse oesophageal spasm were excluded. Swallow responses were categorized by nadir LOSP. For each category of nadir LOSP, WA at the distal 2 recording sites were grouped into bins of 10 mmHg and the proportion of waves in each bin associated with a normal bolus presence time (BPT) was determined. Nadir LOSP, distal BPT, total bolus transit time and the proportion of impaired oesophageal clearance in patients with NOD were greater than those of healthy subjects and patients with GOR. Overall, responses with impaired oesophageal clearance had significantly lower WA (54 ± 1 vs 81 ± 1 mmHg; P  < 0.0001) and higher nadir LOSP (2.7 ± 0.4 vs 1.0 ± 0.1 mmHg, P  < 0.001). For each level of nadir LOSP, there was a direct relationship between distal WA and successful bolus clearance of both liquid and viscous boluses from the distal oesophagus. As nadir LOSP increased, the relationship between WA and bolus clearance shifted to the right and higher amplitudes were required to achieve the same effectiveness of clearance. Hypotensive responses with nadir LOSP ≥3 mmHg were less likely to clear than those with nadir LOSP <3 mmHg, for both liquid (7/29 vs 162/276; P  < 0.001) or viscous boluses (11/46 vs 176/279; P  <   0.0001). Nadir LOSP is an important determinant of bolus clearance from the distal oesophagus, particularly in patients with NOD.     

Gastro-oesophageal reflux of liquids and gas during transient lower oesophageal sphincter relaxations

Some transient lower oesophageal sphincter relaxations (TLOSRs) are accompanied by gastro-oesophageal reflux and others are not. We aimed to investigate what factors determine the occurrence and type of reflux during TLOSRs. In 12 healthy subjects prolonged high-resolution manometry was performed. Reflux was detected using pH-impedance monitoring. A total of 219 TLOSRs were detected; no differences were observed between the duration of TLOSRs with liquid-containing reflux (20.2 +/- 1.0 s), gas reflux (17.0 +/- 1.0 s) and no reflux (19.0 +/- 1.0 s). Trans-sphincteric pressure gradient was similar in TLOSRs with liquid reflux (1.6 +/- 0.1 kPa), gas reflux (1.5 +/- 0.1 kPa) and no reflux (1.7 +/- 0.3 kPa). Prevalence, duration and amplitude of oesophageal pre-contractions and sphincteric after-contractions were not different for TLOSRs with and without reflux. The total number of TLOSRs decreased significantly from 8.2 +/- 0.8 in the first to 5.7 +/- 0.5 in the second and 4.4 +/- 0.6 in the third 70-min recording period. The number of TLOSRs accompanied by liquid-containing reflux decreased from 4.7 +/- 0.9 to 3.0 +/- 0.4 to 1.6 +/- 0.4, while the numbers of TLOSRs with gas reflux remained unchanged (2.1 +/- 0.6-2.1 +/- 0.7-2.2 +/- 0.6). Besides, time after the meal, no differences were observed in the characteristics of TLOSRs with and without gastro-oesophageal reflux. We conclude that factors, other than TLOSR characteristics, are important of whether or not a TLOSR is reflux-related.