Ravinder K. Mittal

Transient lower esophageal sphincter relaxation

RAVINDER K. MITTAL,* RICHARD H. HOLLOWAY,* ROBERTO PENAGINI, § L. ASHLEY BLACKSHAW, t and JOHN DENT* *Department of Internal Medicine, University of Virginia, Charlottesville, Virginia; *Gastrointestinal Medicine, Royal Adelaide Hospital, Adelaide, South Australia, Australia; and §Cattedra di Gastroenterologia, Istituto di Scienze Mediche, University of Milan, IRCCS Ospedale Maggiore, Milan, Italy

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.

Sustained esophageal contraction: A marker of esophageal chest pain identified by intraluminal ultrasonography

BACKGROUND & AIMS Intraluminal pressure recording systems have not demonstrated predictable esophageal motor correlates of unexplained chest pain. This study used continuous high-frequency intraluminal ultrasonography to characterize esophageal contraction at the time of spontaneous and provoked chest pain. METHODS Intraluminal pressure, pH, and ultrasound images of the esophagus were recorded for a maximum of 24 hours in 10 subjects with unexplained chest pain. Changes in esophageal muscle thickness were measured as a marker of muscle contraction. Ten additional subjects with suspected esophageal chest pain were studied after edrophonium chloride injection to provoke symptoms. Ten healthy subjects were studied as controls. RESULTS Eighteen of 24 spontaneous chest pain episodes were preceded by a sustained esophageal contraction (SEC) detected on ultrasonography (mean duration, 68.0 seconds). This motor pattern was not accompanied by changes in intraluminal pressure. Four of 24 asymptomatic control periods were accompanied by SEC, although these contractions were of shorter mean duration (29.0 seconds; P < 0.001). SEC was observed in 5 subjects with a positive chest pain response to edrophonium and in none of the 5 subjects with a negative response. SEC was not detected in normal subjects. CONCLUSIONS There is a strong temporal correlation between a previously unrecognized esophageal motor event, SEC, and both spontaneous and provoked esophageal chest pain.

Sleep and nocturnal acid reflux in normal subjects and patients with reflux oesophagitis.

Nocturnal gastro-oesophageal reflux may be important in the pathogenesis of reflux oesophagitis. This study aimed to determine whether: (1) gastro-oesophageal reflux occurs during sleep in patients with reflux oesophagitis and, if so, to explore the mechanism, and (2) the sleep pattern of patients with oesophagitis is different from that of control subjects. After a standard evening meal, simultaneous manometric, oesophageal pH, and polysomnographic recordings were obtained in 11 patients with endoscopic oesophagitis and 11 control subjects. Patients with gastrooesophageal reflux disease had significantly more total reflux episodes throughout the nocturnal monitoring period than control subjects (105 v 6). Ninety two of 105 episodes of gastro-oesophageal reflux in patients occurred during the awake state and 10 during sleep stage II. A number of reflux episodes occurred during brief periods of arousal from the various sleep stages. Of the 105 reflux events recorded in patients, 42 were induced by transient lower oesophageal sphincter relaxation, 20 by stress reflux, 22 by free reflux mechanisms, and in 21 the mechanism was unclear. The sleep pattern and the time spent in each sleep stage was not different between the two groups. It is concluded that the awake state is crucial for the occurrence of nocturnal reflux episodes in normal subjects as well as in patients with reflux oesophagitis and that the difference between the frequency of gastro-oesophageal reflux between normal subjects and patients cannot be explained by different sleep patterns.

Effect of Atropine on the Frequency of Reflux and Transient Lower Esophageal Sphincter Relaxation in Normal Subjects

BACKGROUND & AIMS Low basal lower esophageal sphincter (LES) pressure is believed to be an important mechanism of reflux. The effects of atropine on the frequency and mechanisms of gastroesophageal reflux under the experimental conditions of a low basal LES pressure in 13 normal subjects were studied. METHODS LES pressure, esophageal pressures, esophageal pH, and crural diaphragm electromyogram were recorded simultaneously in the postprandial period for 30 minutes before and two 30-minute periods after the injection of atropine. RESULTS Atropine reduced the basal LES pressure from 16.4 +/- 3 to 8.7 +/- 2 mm Hg. The frequencies of reflux in the control and two postatropine periods were 3.5 +/- 0.5, 0.4 +/- 0.2, and 0.8 +/- 0.3, respectively (P < 0.05). The frequencies of transient LES relaxations decreased from 3.5 +/- 0.5 in the control to 0.4 +/- 0.2 and 1.5 +/- 0.4 in the two postatropine periods (P < 0.05). Transient LES relaxation and associated inhibition of the crural diaphragm was the major mechanism of reflux under conditions of low LES pressure induced by atropine. CONCLUSIONS Atropine-induced low LES pressure does not predispose to reflux in normal healthy subjects. Atropine reduces the frequency of reflux by its inhibitory effect on the frequency of transient LES relaxation.

Electrical and Mechanical Inhibition of the Crural Diaphragm During Transient Relaxation of the Lower Esophageal Sphincter

Electrical and mechanical correlates of crural diaphragm activity during swallow-induced and transient lower esophageal sphincter relaxation were monitored in 12 healthy subjects. Simultaneous esophageal manometric, pH, and crural diaphragm electromyogram recordings were performed for 1 hour in the postprandial period. Swallow-induced lower esophageal sphincter relaxation was associated with minimal inhibition of the crural diaphragm, but transient lower esophageal sphincter relaxation was accompanied by marked inhibition of the crural diaphragm. The degree of lower esophageal sphincter relaxation appeared to correlate with the degree of crural diaphragm inhibition during transient lower esophageal sphincter relaxation. Inhibition of crural diaphragm during transient lower esophageal sphincter relaxation may play an important role in facilitating flow across the gastroesophageal junction.

Effect of a catheter in the pharynx on the frequency of transient lower esophageal sphincter relaxations

Transient relaxation of the lower esophageal sphincter (LES) is observed fairly frequently during prolonged continuous monitoring of the LES. The aim of this study was to test whether the presence of a catheter in the pharynx through the stimulation of mechanoreceptors may induce transient LES relaxation. LES and esophageal pressure recordings were obtained for 1 hour in six subjects with a manometric catheter placed via a gastrostomy tube. Swallowing was monitored by submental electromyographic recording. Additional recordings were obtained in these subjects with a catheter placed in the pharynx for 1 additional hour. Transient LES relaxations were recorded in both study periods, i.e., with and without a catheter in the pharynx. The frequency of transient LES relaxations was significantly higher in the presence of manometric catheters in the pharynx (6.4 +/- 2.2 vs. 2.0 +/- 1.1 total LES relaxations). The frequency of transient LES relaxation during the first and second hour after placement of the manometric catheter in a group of seven healthy subjects was not significant different. It is concluded that the pharynx is one of the sites that may mediate the induction of transient LES relaxation.

Review article: acidity and volume of the refluxate in the genesis of gastro-oesophageal reflux disease symptoms

Background A number of mechanisms, other than acid reflux, may be responsible for the symptoms of gastro‐oesophageal reflux disease.

Dysfunction of the longitudinal muscles of the oesophagus in eosinophilic oesophagitis

Background: Oesophageal motility, as measured by manometry, is normal in the majority of patients with eosinophilic oesophagitis (EO). However, manometry measures only the circular muscle function of the oesophagus. The goal of the present study was to assess circular and longitudinal muscle function during peristalsis in patients with EO. Methods: Ultrasound imaging and manometry were simultaneously acquired during swallow-induced peristalsis in patients with EO and controls to measure the longitudinal muscle and circular muscle contraction, respectively. A probe with an ultrasound transducer was positioned 2 cm and then 10 cm above the lower oesophageal sphincter and five, 5 ml water swallows were recorded before and after edrophonium. Results: There is no difference in the incidence of swallow-induced peristalsis and manometric pressures (a marker of circular muscle contraction) between controls and patients with EO. However, changes in the muscle thickness (a marker of longitudinal muscle contraction) are markedly diminished in patients with EO, at both 2 and 10 cm above the lower oesophageal sphincter. The longitudinal muscle response to edrophonium is markedly blunted in patients with EO. Normal subjects demonstrate synchrony between the circular and longitudinal muscle contraction during peristalsis that is affected by edrophonium. On the other hand, patients with EO demonstrate mild asynchrony of circular and longitudinal muscle contraction during swallow-induced contractions that is not altered by edrophonium. Conclusions: In patients with EO, there is selective dysfunction of the longitudinal muscle contraction during peristalsis. It is proposed that the longitudinal muscle dysfunction in EO may contribute to dysphagia.

Prevalence of Increased Esophageal Muscle Thickness in Patients With Esophageal Symptoms

BACKGROUND:Patients with achalasia, diffuse esophageal spasm (DES), and nutcracker esophagus have a thicker muscularis propria than normal subjects. The goal of our study was to determine the prevalence of increased muscle thickness in a group of unselected patients referred to the esophageal function laboratory for evaluation of the symptoms.METHODS:We studied 40 normal subjects and 94 consecutive patients. Manometry and ultrasound images were recorded concurrently, using a special custom-built catheter. Esophageal muscle thickness and muscle cross-sectional area were measured at 2 and 10 cm above the lower esophageal sphincter (LES). Patients were assigned manometric diagnosis and determination was made if they had increased muscle thickness and muscle cross-sectional area.RESULTS:Nearly all patients with well-defined spastic motor disorders, i.e., achalasia, DES, and nutcracker esophagus, revealed (a) an increase in the muscle thickness/cross-sectional area, (b) increase in esophageal muscle thickness/cross-sectional area was also seen, albeit at a lower prevalence rate, in patients with less well-characterized manometric abnormalities, i.e., hypertensive LES, impaired LES relaxation, and ineffective esophageal motility, and (c) 24% of patients with esophageal symptoms but normal manometry were also found to have an increase in muscle thickness/cross-sectional area. Dysphagia was more likely, and heartburn less likely in patients with increased muscle thickness, but there were no differences in chest pain and regurgitation symptoms between the groups.CONCLUSION:We describe, for the first time, increased muscle thickness in patients with esophageal symptoms and normal manometry. We suggest that increased esophageal muscle thickness is likely to be an important marker of esophageal motor dysfunction.