Effects of lidocaine on esophageal secondary peristalsis in humans

Background Secondary peristalsis is important for the clearance of retained food bolus or refluxate from the esophagus. Lidocaine has been used to evaluate the role of mucosa‐mediating pathways of esophageal reflexes in animal model, but its effects on esophageal secondary peristalsis are yet unclear in humans. We aimed to investigate whether esophageal secondary peristalsis can be affected by intraluminal infusion of lidocaine into the esophagus. Methods After a baseline recording esophageal motility, secondary peristalsis was generated by slow and rapid mid‐esophageal injections of air in 13 healthy subjects. Two separate sessions with saline and lidocaine were randomly performed to test their effects on esophageal secondary peristalsis by mid‐esophageal air distension. Key Results Secondary peristalsis can be induced by slow or rapid air infusion. Secondary peristalsis was triggered less frequently in response to rapid air distension after lidocaine infusion (P = 0.001). After lidocaine infusion, the threshold volume to generate secondary peristalsis was significantly increased during rapid (P = 0.001), but not slow air infusions (P = NS). Infusion of lidocaine or saline did not affect pressure wave amplitude or duration during rapid and slow air infusions (P = NS). Conclusions & Inferences We have demonstrated selectively inhibitory effect of lidocaine on the triggering of esophageal secondary peristalsis during acute gaseous esophageal distension. The data suggest that part of the activation of secondary peristalsis is probably mediated by lidocaine‐sensitive mechanoreceptors; however, the infusion of lidocaine does not lead to any motility change in secondary peristalsis induced by either slow or rapid air infusions.     

Effects of capsaicin‐containing red pepper sauce suspension on esophageal secondary peristalsis in humans

Background Capsaicin‐sensitive afferents have been implicated in the modulation of gastrointestinal sensorimotor functions. Secondary peristalsis is important for the clearance of retained refluxate or material from the esophagus. The aim of this study was to evaluate the effects of capsaicin‐containing red pepper sauce suspension on esophageal secondary peristalsis in healthy adults. Methods After a baseline recording of esophageal motility, secondary peristalsis was generated by slow and rapid mid‐esophageal injections of air in 10 healthy subjects. Two separate sessions with saline and capsaicin‐containing red pepper sauce were randomly performed to test their effects on esophageal secondary peristalsis. Key Results Infusion of capsaicin significantly increased pressure wave amplitude during rapid (P = 0.002) and slow air infusions (P = 0.01). After capsaicin, the threshold volume to generate secondary peristalsis was significantly decreased during rapid (P < 0.05) and slow air infusions (P = 0.02). Infusion of saline did not affect any parameters of secondary peristalsis during rapid or slow air infusion. The administration of capsaicin was accompanied by the occurrence of heartburn in all subjects. Conclusions & Inferences The acute administration of capsaicin‐containing red pepper sauce suspension enhances sensitivity to distension‐induced secondary peristalsis and facilitates secondary peristaltic contractility. These data suggest the involvement of capsaicin‐sensitive afferents in the modulation of esophageal distension‐induced secondary peristalsis in humans.     

Control of esophageal distension‐induced secondary peristalsis by the GABAB agonist baclofen in humans

Background Secondary peristalsis is important for the clearance of retained food bolus or refluxate from the esophagus. The effects of the gamma aminobutyric acid receptor type B (GABA_B) agonist on secondary peristalsis remain unclear in humans. We aimed to investigate the effect of a GABA_B agonist baclofen on esophageal secondary peristalsis. Methods After a baseline recording of esophageal motility, secondary peristalsis was generated by slow and rapid mid‐esophageal injections of air in 15 healthy subjects. Two separate sessions with 40 mg oral baclofen or placebo were randomly performed to test their effects on secondary peristalsis. Key Results Baclofen increased the threshold volume for triggering secondary peristalsis during slow air distension (P = 0.003) and rapid air distension (P = 0.002). Baclofen reduced the rate of secondary peristalsis by rapid air distension from 90% to 30% (P = 0.0002). Baclofen increased basal lower esophageal sphincter pressure (P = 0.03). Baclofen did not affect any of peristaltic parameters during primary or secondary peristalsis. Conclusions & Inferences This study provides an evidence for inhibitory modulation of esophageal secondary peristalsis by the GABA_B agonist baclofen. Activation of secondary peristalsis is probably modulated by GABA_B receptors; however, baclofen does not lead to any motility change in secondary peristalsis.     

MMC-related duodenojejunal antegrade and retrograde peristalsis in humans

Abstract According to recent manometric studies the last part of phase III of the migrating motor complex (MMC) shows the features of a retroperistaltic pump in the proximal duodenum in most healthy humans. In the present study, individual contractions in phase II and phase III of the MMC were investigated in ten healthy subjects (four males, six females), focusing on the distal duodenum and the jejunum. Motility was recorded on two different days with eight-channel catheters. On one day a standard antroduodenojejunal fasting recording was performed for 5 h, allowing detailed analysis of pressure waves in the proximal duodenum. On another day a two-station measurement was performed in the proximal jejunum and the distal duodenum. The propagated pressure waves were analysed for late phase II (last 30 min) and for the first and the last part (I min) of phase III in the three intestinal segments. Antegrade peristalsis predominated at all levels in phase II and in the first part of phase III. In contrast, 84 ± 11% of all propagated contractions were retrograde in the last part of phase III in the proximal duodenum and 75 ± 16% in the distal duodenum. The proportions of retrograde contractions in early phase III and in late phase III differed significantly, from 11 ± 11% to 84 ± 11% and from 32 ± 16% to 75 ± 16% in the proximal and distal duodenum, respectively (P < 0.01 and P < 0.05). In the proximal jejunum such retroperistalsis was not observed, neither in the beginning nor at the end of phase III. In phase II the proportions of retrograde pressure waves were small (3–10%) in the three segments studied. The migration velocity of the pressure waves showed a gradient in this phase, with the lowest values in the jejunum. It is concluded that the last part of phase III shows the pressure pattern of a retroperistaltic pump through out the duodenum. In contrast, no distinct MMC-related retroperistalsis was observed in the jejunum.     

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.     

Postprandial peristalsis in the human duodenum

MMC-related retroperistalsis is a cyclical phenomenon in the duodenum linked to phase III. The aim of this study was to elucidate the direction of propagation of juxtapyloric duodenal pressure waves in the postprandial state in healthy humans and to compare with the contractions in the interdigestive phase II. Antroduodenal manometry was performed in 11 healthy subjects. Individual pressure waves propagating along a 6-cm duodenal segment were analysed with respect to the proportions of antegrade and retrograde propagation in the four duodenal subsegments (D1–D2) to (D4–D5), each subsegment being 15 mm. A test meal was given 30 min after a phase III had passed and motility recording continued for 60 min after the meal. During both the first and the second 30-min period of postprandial recording the proportion of retrograde pressure waves was larger just distal to the pylorus, (D1–D2), 40% (23–68) and 50% (23–68), respectively, compared to the distal part, (D4–D5), of the duodenal segment, 29% (12–30) and 10%(10–24), respectively (P < 0.05 and 0.01). In contrast, during late phase II of the interdigestive state antegrade pressure waves predominated in all four duodenal subsegments. We conclude that in the postprandial state a high proportion of the duodenal pressure waves (40–50%) is retrograde in the immediate juxtapyloric area while antegrade contractions predominate at a distance 5–6 cm distal to the pylorus. These manometric data together with recent observations of postprandial transpyloric liquid flow, indicate that retrograde duodenogastric propelling of contents may be an important determinant for the gastric emptying rate.     

Identification of impaired oesophageal bolus transit and clearance by secondary peristalsis in patients with non-obstructive dysphagia

Abstract  Impaired secondary peristalsis has been shown in non-obstructive dysphagia (NOD). The relationship between such changes and alterations in bolus transport has not been studied. The aim of this study was to evaluate the integrity and characteristics of oesophageal bolus transit by secondary peristalsis in NOD patients with multichannel intraluminal impedance (MII). Eleven healthy volunteers and 10 consecutive patients underwent combined MII recording and manometry. Secondary peristalsis was stimulated by mid-oesophageal injections of saline. Values for bolus presence time at each of the recording sites and bolus transit time were calculated. Bolus transit was considered to be complete when impedance defined complete bolus clearance at all recording sites. Secondary peristaltic responses were triggered significantly less frequently in patients with NOD than in controls ( P  < 0.001). The proportion of secondary peristalsis demonstrating complete bolus transit was lower in NOD patients than in controls ( P  < 0.001). Oesophageal bolus transit time by secondary peristalsis was longer in NOD patients than in controls ( P  = 0.005), as was bolus presence time at each of the recording sites ( P  < 0.05). When compared with controls, NOD patients demonstrated a higher proportion of incomplete bolus transit in response to normal secondary peristalsis ( P  < 0.001). Abnormal bolus transit occurred more often associated with ineffective and synchronous responses than normal responses in both groups studied ( P  < 0.001). Multichannel intraluminal impedance identifies functional defects of oesophageal bolus clearance by secondary peristalsis in NOD patients and such defects are characterized by a longer oesophageal dwell and a prolonged clearance time.     

Oesophageal pressure–cross-sectional area distributions and secondary peristalsis in relation to subclassification of systemic sclerosis

The aim of the present study was to correlate the severity of oesophageal motor dysfunction with the severity of cutaneous disease in systemic sclerosis (SS). Patients were divided into three groups based on the degree of skin involvement: type I, acrosclerosis distal to the wrist; type II, scleroderma extending above the wrist in proximal direction; type III, diffuse cutaneous systemic sclerosis. Impedance planimetry employing distensions with pressures up to 5 kPa with the concomitant measurement of oesophageal cross-sectional area (CSA) was used in combination with standard oesophageal manometry. Measurements were made at 7 and 15 cm above the lower oesophageal sphincter (LOS). Thirty patients (16 type I, six type II and eight type III patients) and 23 normal controls were included. LOS pressure was lower in SS patients than in normal patients, with the lowest values in type III. The CSAs were higher in SS patients than in controls at both sites (P < 0.001). The CSAs at the distal site were highest in type III, as compared to type I and II (P < 0.03). The CSA at the highest induced pressure (5.0 kPa) was 613 +/- 45, 719 +/- 79, and 808 +/- 115 mm2 in types I, II and III, respectively. No differences in CSA were found at the proximal site between the three types of SS. The distensibility did not differ between SS and normal patients at the distal site. The distensibility was lowest in SS patients (P < 0.001) at the proximal distension site. The distensibility did not vary with the type of SS at either site. Significant differences in contraction frequency of the secondary peristalsis as function of wall tension were demonstrated between the SS patients and controls at the distal site (P < 0.05). No differences were found at the proximal site. The contraction frequency and amplitude at the distal and proximal sites did not differ among the three types. In conclusion for most parameters studied, SS patients differed from normal patients. Among SS types, the most pronounced changes were found in type III.     

High-resolution analysis of the duodenal interdigestive phase III in humans

To study the spatial organization of the propagating pressure waves of duodenal phase III, we performed fasting antroduodenal high-resolution manometry with a 16-channel catheter in 12 healthy subjects. The phase III pressure waves diverged in an anterograde and retrograde direction from the start site of each pressure wave. The pressure waves maintained this configuration as the activity front moved distally in the duodenum. The start site of the pressure waves moved gradually to a point approximately 12 cm (median) distal to the pylorus and remained at this point for about 40% of the phase III time before moving further distally. The length of retrograde pressure wave propagation increased to 6 cm (median) as the pressure wave origin moved aborally to a point 10-14 cm distal to the pylorus, and then decreased when the origin of pressure waves reached the distal end of the duodenum. Bidirectional pressure waves dominated in both retrograde and anterograde activity fronts. Three pressure-wave mechanisms behind the duodenal phase IV were observed. Isolated pyloric pressure waves were absent during late duodenal phase III retroperistalsis. Thus, a number of new features of the duodenal phase III-related motility were observed using high-temporospatial resolution recordings.     

Effect of 5‐HT4 receptor agonist mosapride citrate on rectosigmoid sensorimotor function in patients with irritable bowel syndrome

Background The 5‐HT₄ receptor agonist, mosapride citrate, accelerates gastric emptying. However, the effect of mosapride on colonic function has not been well investigated. We examined whether mosapride changes rectosigmoid motility and perception in patients with irritable bowel syndrome (IBS). Methods Thirty‐seven patients with IBS and 18 healthy subjects were studied. All subjects underwent a rectosigmoid barostat test to measure pain perception to intraluminal distention and resting smooth muscle motility for 20 min in the fasting state. Irritable bowel syndrome patients were then randomly assigned to receive either mosapride 15 mg (n = 19) or placebo (n = 18) orally with 200 mL water. Rectosigmoid motility and perception were measured again for 60 min following dosing. Rectosigmoid tone and contractility were evaluated in each 10‐min period. Key Results The pain threshold in the patients was significantly lower than that in controls (P < 0.01). There were no differences between mosapride and placebo groups in pain threshold, barostat bag volume, or number of contractions at baseline. Mosapride significantly decreased the mean bag volume (P < 0.01; group × period interaction by two‐way anova ) and increased the mean number of contractions (P < 0.05) compared with placebo, but did not affect the perception. In IBS patients with constipation (i.e., excluding diarrhea‐predominant subjects), mosapride (n = 13) increased rectosigmoid tone (P < 0.01) and contractions (P < 0.05) more than placebo (n = 14). Conclusions & Inferences Mosapride stimulates colonic motility without any adverse effect. These findings suggest that mosapride may have the potential to treat IBS patients with constipation and/or functional constipation. Further clinical trials are warranted to confirm the efficacy of this agent.     

Botulinum toxin injection in dysphagia syndromes with preserved esophageal peristalsis and incomplete lower esophageal sphincter relaxation

Background Botulinum toxin injection into the lower esophageal sphincter (LES) treats dysphagia syndromes with preserved peristalsis and incomplete LES relaxation (LESR). We evaluated clinical and esophageal motor characteristics predicting response, and compared duration of efficacy to similarly treated achalasia patients. Methods Thirty‐six subjects (59 ± 2.2 years, 19F/17M) with incomplete LESR on high resolution manometry (HRM) treated with botulinum toxin injection were identified. Individual and composite symptom indices were calculated, and HRM characteristics extracted. Symptom resolution for 6 months was a primary outcome measure, and repeat botulinum toxin injection, dysphagia recurrence or employment of alternate therapeutic approaches were secondary outcome measures. Duration of response was compared using Kaplan‐Meier survival curves to a historical cohort of similarly treated achalasia subjects. Key Results Response lasted a mean of 12.8 ± 2.3 months. Symptom relief for >6 months was seen in 58.3%; short (<6 months) response was associated with younger age, higher chest pain index, and esophageal body spastic features (P ≤ 0.04). On multivariate logistic regression, chest pain, younger age and contraction amplitudes >180 mmHg independently predicted <6 months relief (P < 0.05 for each). On survival analysis, relief with a single injection extended to 1 year in 54.8% and 1.5 years in 49.8%, statistically equivalent to that reported by 42 similarly treated achalasia subjects (59 ± 3.2 years, 24F/18M). Symptom relief was more prolonged compared to achalasia when repeat injections were performed on demand (P = 0.003). Conclusions & Inferences Botulinum toxin injections can provide lasting symptom relief in dysphagia syndromes with incomplete LESR. Prominent perceptive symptoms and non‐specific spastic features may predict shorter relief.     

The effect of mosapride citrate on proximal and distal colonic motor function in the guinea-pig in vitro.

Mosapride citrate (mosapride), a substituted benzamide, is a selective 5-HT(4) receptor agonist, and is known to have prokinetic properties on the stomach. However, it is unclear whether mosapride also has a prokinetic effect on the colon. We previously found that mosapride significantly shortened colonic transit time in the guinea-pig, an animal with a distribution of colonic 5-HT(4) receptors similar to that of a human. So, we aimed to separately evaluate the effect of mosapride on proximal and distal colonic motor function in the guinea-pig. Proximal (approximately 8 cm from the ileocolic junction) and distal colon (approximately 8 cm from the anus) were removed. Both ends of the colon were connected to a chamber containing a Krebs-Henseleit solution. To measure colonic transit time, artificial faeces were inserted into the oral side of the lumen and moved towards the anal side by intraluminal perfusion via a peristaltic pump. A total of 6 cm of transit was observed and time was measured in 2 cm increments. A tissue bath study, using electrical stimulation, was performed to estimate the contractile activity of the circular musculature of the colon. Immunohistochemical staining for 5-HT(4) receptors was performed in the myenteric plexus and circular muscle in both proximal and distal colon, and the stained area was measured using a microscope and computer software. Mosapride enhanced contraction at 10(-9) to 10(-7) mol L(-1), coinciding with rapid transit both in proximal and distal colon. This pattern was more prominent in proximal colon. At the high dose (10(-6) mol L(-1)) mosapride had little or no effect on colonic contraction. This stimulatory effect was attenuated by GR113808, atropine and tetrodotoxin. In the myenteric plexus, the density of 5-HT(4) receptors was significantly greater in the proximal colon than in the distal colon, but in circular muscle the density was greater in the distal colon. Thus, mosapride accelerates transit through increased contraction in the proximal colon more than distal colon. The different distribution of neuronal and muscular 5-HT(4) receptors may support these findings. Therefore, mosapride may be a useful alternative to tegaserod and cisapride for constipation.     

Refining the criterion for an abnormal Integrated Relaxation Pressure in esophageal pressure topography based on the pattern of esophageal contractility using a classification and regression tree model

Background The Integrated Relaxation Pressure (IRP) is the esophageal pressure topography (EPT) metric used for assessing the adequacy of esophagogastric junction (EGJ) relaxation in the Chicago Classification of motility disorders. However, because the IRP value is also influenced by distal esophageal contractility, we hypothesized that its normal limits should vary with different patterns of contractility. Methods Five hundred and twenty two selected EPT studies were used to compare the accuracy of alternative analysis paradigms to that of a motility expert (the ‘gold standard’). Chicago Classification metrics were scored manually and used as inputs for MATLAB? programs that utilized either strict algorithm‐based interpretation (fixed abnormal IRP threshold of 15 mmHg) or a classification and regression tree (CART) model that selected variable IRP thresholds depending on the associated esophageal contractility. Key Results The sensitivity of the CART model for achalasia (93%) was better than that of the algorithm‐based approach (85%) on account of using variable IRP thresholds that ranged from a low value of >10 mmHg to distinguish type I achalasia from absent peristalsis to a high value of >17 mmHg to distinguish type III achalasia from distal esophageal spasm. Additionally, type II achalasia was diagnosed solely by panesophageal pressurization without the IRP entering the algorithm. Conclusions & Inferences Automated interpretation of EPT studies more closely mimics that of a motility expert when IRP thresholds for impaired EGJ relaxation are adjusted depending on the pattern of associated esophageal contractility. The range of IRP cutoffs suggested by the CART model ranged from 10 to 17 mmHg.