Gastric Electrical Stimulation Significantly Increases Canine Lower Esophageal Sphincter Pressure

This study determined the effect of low-frequency and high-frequency gastric electrical stimulation (GES) on canine lower esophageal sphincter (LES) pressure and also evaluated the effect of such stimulation on neurohumoral factors that modulate LES pressure. Eight dogs were fitted with stimulation wires along the greater curvature of the stomach. A sleeve device measured LES pressure before, during, and after GES, and regulatory peptides were measured during fasting and after a meal. A consistent and significant rise in LES pressure was observed during GES, and it was sustained after GES was discontinued. Plasma concentration and area under the curve of pancreatic polypeptide, motilin, gastrin and neurotensin were not affected by GES. We conclude that acute low- and high-frequency GES significantly increases LES pressure. This effect may not be modulated by efferent vagal activity or release of regulatory peptides.     

Effect of Endogenous Hyperprolactinemia on Human Lower Esophageal Sphincter Pressure

The cause of gastroesophageal reflux occurring during pregnancy is not completely understood but may be related to changes in the hormonal environment specifically related to pregnancy. To evaluate the possible role of prolactin, one of the hormones elevated during pregnancy, we studied the effect of endogenously elevated serum prolactin concentrations, induced by I.V. thyrotropin-releasing hormone (TRH), on lower esophageal sphincter pressure (LESP) in normal subjects. Elevated prolactin concentrations (P less than 0.0001), did not change LESP over a 60-minute period. Serum gastrin concentration did not change significantly at any time during the study. We conclude: 1. acute elevations of serum prolactin comparable to the concentrations that occur during pregnancy did not change LESP; 2. there is no evidence that the hypothalamic regulating factor TRH affects serum gastrin concentration in man.     

Relationship of Intraluminal pH and Pressure within the Lower Esophageal Sphincter

To determine the relationship between lower esophageal sphincter (LES) intraluminal pressure and its intraluminal pH, we studied six healthy volunteers. We recorded intraluminal pressure and pH concurrently using rapid pull-through, slow pull-through, and station pull-through, as well as, rapid push-through and slow push-through techniques. The results showed that LES length was 35 +/- 4 (SE) mm by RPT and 30 +/- 3 mm by SPT. The pressure was maximal in the proximal half of the LES. On rapid pull-throughs, the intraluminal pH rose from about 1.5 to reach a value of about 2.5 at the peak of the high pressure zone. With continued withdrawal into the esophageal body, the recorded pH rose minimally to about 3-4. On push-throughs, the pH recorded along the LES was the same as that of the esophageal body. After the electrode cleared the LES, the pH abruptly fell to gastric pH. During station pull-through with the electrode 0.5-1.5 cm proximal to the distal LES margin, transient pH drops were observed with swallows. With rapid swallows, however, the pH drop did not occur until after the last swallow. This finding suggests that the pH drops with swallows were due to axial LES movement rather than gastroesophageal acid reflux. We conclude that 1) the relationship of the gastroesophageal pH transition zone and LES high pressure zone is better defined by a sphincter push-through than a pull-through; 2) the transition between gastric and esophageal pH occurs either at or slightly distal to the distal LES margin; and 3) swallow-induced axial LES movement may cause spurious recording of acid reflux when the pH probe is positioned within the distal half of the LES.     

Effect of Thyrotropin-Releasing Hormone on the Human Lower Esophageal Sphincter Pressure

The effect of thyrotropin-releasing hormone (TRH) on the human lower esophageal sphincter pressure (LESP) was studied in eight healthy volunteers. After injection of 200 μg TRH intravenously LESP fell from 10.6 (SD, 1.6) to 6.4 (SD, 2.3) mm Hg after 5 min, to 7.5 (SD, 3.0) mm Hg after 10 min, and to 8.0 (SD, 2.7) mm Hg after 15 min. These data were compared with change in LESP after injection of 0.9% NaCl (no. = 8), and we found significant difference (p < 0.05) in LESP after 5, 10, and 15 min. Whether this response was a direct myogenic effect on the LES or an indirect action via the dopaminergic nerve system requires further investigation.     

Reversal of Negative Pressure Ventilation-Induced Lower Esophageal Sphincter Dysfunction with Metoclopramide

We have previously demonstrated that lower esophageal sphincter (LES) dysfunction is induced in healthy volunteers placed in negative pressure body ventilators. This is important, because regurgitation of gastric contents and peptic esophagitis are frequent complications of the use of such ventilators. The present study was conducted to determine whether LES dysfunction during the use of these ventilators also occurs in patients with chronic respiratory failure, and whether this dysfunction can be pharmacologically reversed. Seven patients with documented chronic respiratory failure due to COPD were studied. After an overnight fast, esophageal, LES, and gastric pressures were simultaneously recorded in the unassisted state and during mechanically assisted ventilation, after which 10 mg iv metoclopramide were administered to each patient, and pressure recordings were continued for 1 h more. In all seven patients, baseline LES pressures were in the normal range. During the inspiratory cycle of mechanical ventilation, five of the seven patients demonstrated a significant reduction in LES pressure, whereas it was unchanged in the other two. Within 15 min of metoclopramide administration, there was an increase in LES pressure to baseline levels in the five patients in which a significant decrease in LES pressure had occurred. Metoclopramide did not have any effect on the LES pressure of the other two patients. Thus, we conclude that in patients with chronic respiratory failure, as in normals, there is a subset of individuals in whom negative pressure mechanical ventilatory assistance induces dysfunction of the LES, and that this dysfunction is reversible with metoclopramide.     

Four-Channel Sleeve Catheter for Prolonged Measurement of Lower Esophageal Sphincter Pressure

A sleeve catheter capable of monitoring thelower esophageal sphincter (LES) pressure in fourquadrants at right angels has been developed. Thepresent study used this four-quadrant sleeve catheter toassess radial asymmetry in LES in the supine, prone,and upright positions. The results in 37 normal subjectswere compared with those of a conventional side-holecatheter and a Dent sleeve catheter. In vitro studies showed that the response rate of eachradially oriented sleeve is comparable to the Dentsleeve. Mean pressures were not significantly differentbetween the three different types of catheter. The four-quadrant sleeve catheter consistentlydetected a higher LES pressure in the left posteriorposition, regardless of body position. The four quadrantsleeve catheter can be used to record LES pressure from four different quadrants of the LES forprolonged periods.     

Reproducibility of the Rapid Pull-Through Technique for Categorizing Lower Esophageal Sphincter Pressure

Duplicate measurements of basal lower esophageal sphincter (LES) pressure using a triple-lumen catheter and the rapid pull-through technique (RPT) were performed in 250 consecutive patients to determine their reproducibility for categorizing LES pressures as normal, hypertensive, or hypotensive. For all subjects, mean LES pressure did not differ for the two measurements (25.3 +/- 1.0 vs. 26.2 +/- 1.0 mm Hg, p greater than 0.5), but the correlation coefficient was only modest (r = 0.73). Reproducibility of categorization was 92% (230 of 250 subjects), and was best for subjects with normal (170/179, 95%) or hypotensive (24/26, 92%) values (for hypertensives: 36/45, 80%). Interstudy variability was least for the hypotensive group (1.8 +/- 0.2 mm Hg) and greatest for the hypertensive group (16.4 +/- 1.9 mm Hg). Likewise, the range of individual values from the triple-lumen catheter was least for the hypotensive subjects (4.7 +/- 0.7 mm Hg) and greatest for those with hypertensive LES pressure (32.5 +/- 2.6 mm Hg). These data show that, despite its interstudy variability, the RPT reproducibly categorizes basal LES pressure in greater than 90% of cases. The technique appears least reliable in determining hypertensive LES pressure, where diaphragmatic contraction may most significantly contribute to measurement variability.     

Abnormal Lower Esophageal Sphincter Pressure Responses in Patients with Orange Juice-Induced Heartburn

The mechanism of orange juice-induced heartburn is unclear. One previous uncontrolled study showed only a transient fall in lower esophageal sphincter pressure IL ESP) after orange juice and suggested that orange juice-induced heartburn was caused by a direct effect on the esophageal mucosa. We studied the effect of orange juice on LESP by comparing symptomatic patients with asymptomatic controls. LESP was measured for 10 min before and 60 min after the ingestion of 250 ml of orange juice in eight patients with orange juice-induced heartburn and in seven asymptomatic controls. Before orange juice ingestion, LESPs were similar in the symptomatic and asymptomatic groups, 18.3 and 17.8 mm Hg, respectively (not significant). In the control group, LESP increased by at least 5 mm Hg at 20 min after orange juice ingestion and remained elevated for the duration of the observation. In the symptomatic group there was no significant change in LESP despite the onset of heartburn. This was significantly different from the control group ( p < 0.01). We conclude that LESP response to orange juice is different in those who develop heartburn from those who do not. This abnormal response may make these patients more prone to reflux, but the numerical change in LESP is small and the L ESP remains within the normal range. We believe that gastroesophageal reflux is unlikely to be the mechanism of orange juice-induced heartburn.     

Different Effects of White and Red Wine on Lower Esophageal Sphincter Pressure and Gastroesophageal Reflux

Background: White wine and beer induce gastroesophageal reflux (GER). We investigated the effects of white and red wine on lower esophageal sphincter pressure (LESP) and GER. Methods: Twenty healthy volunteers received 300 ml white wine, red wine, or water together with a standardized meal. The LESP was continuously monitored with a Dent sleeve the 1st h postprandially, and the esophageal pH measured with a glass pH electrode. Results: The LESP was decreased after intake of white wine (median, 14.9 mmHg; range, 5.6-19.5 mmHg) compared with red wine (20.4 mmHg; 13.1-22.3 mmHg; P &lt; 0.05) and tap water (19.5 mmHg; 16.2-29.1 mmHg; P &lt; 0.01). The fraction time esophageal pH &lt;4 was increased after both alcoholic beverages compared with tap water (0.9%; 0.2-5.8%; P &lt; 0.01 versus white wine, P &lt; 0.05 versus red wine) with a greater fraction time after white wine (13.2; 0.3-58.1) than after red wine (2.3; 0.7-24.4; P &lt; 0.05). The decreased sphincter pressure after white wine was accompanied by a change in the reflux pattern with increased `stress reflux' and the occurrence of `free reflux'. Conclusion: White wine and red wine exert different effects on LESP and GER.     

Effect of Intragastric Amino Acids on Lower Esophageal Sphincter Pressure and Serum Gastrin in Man

The effects of the intragastically administered individual L-amino acids, phenylalanine, tryptophan, glycine, aspartic acid, and leucine on lower esophageal sphincter (LES) pressure and serum gastrin concentration were studied in normal subjects. On separate days and in random, double-blind fashion, 13 adult male subjects received isotonic 0.1 M concentration of amino acids and saline, at pH 5.5 in a volume of 600 ml by rapid intragastric instillation over 5 min. LES pressure and serum gastrin concentration were monitored basally and then at frequent intervals for 90 min. Only tryptophan had a significant effect on LES pressure when compared with saline, decreasing LES pressure from 20 to 60 min after administration (p less than 0.01). Only phenylalanine and tryptophan produced significant stimulation of serum gastrin levels with peak increases above basal occurring 30 min after administration (p less than 0.05). It is concluded that: aspartic acid, leucine and glycine produced no significant changes in LES pressure or serum gastrin level; tryptophan and phenylalanine significantly increased serum gastrin concentration; tryptophan significantly decreased LES pressure whereas phenylalanine had no effect; the mechanism of inhibition of LES pressure by tryptophan is not defined and may be mediated by neural or hormonal pathways possibly involving a duodenal receptor.     

Effect of Diazepam on the Lower Esophageal Sphincter

The effect of diazepam on the lower esophageal sphincter (LES) pressure was studied in a controlled randomized double-blind protocol. Twenty-five patients received intravenous saline, diazepam 5 mg. and diazepam 10 mg. on different days. Diazepam 5 mg. and diazepam 10 mg. caused a mean peak reduction in LES pressure of 18.9 and 37.8% respectively. The peak reduction in LES pressure was dose-related and lasted approximately seven minutes. Awareness of diazepam's ability to significantly lower LES pressure is needed to avoid the possibility of falsely diagnosing reflux by endoscopy. The mechanism whereby diazepam lowers LES pressure is not known, however, diazepam may be acting as a smooth muscle relaxant since myogenic infiuences have been implicated in the genesis of LES pressure.     

The Effect of Verapamil on the Lower Esophageal Sphincter Pressure in Normal Subjects and in Achalasia

Verapamil hydrochloride is an organic calcium antagonist that is known to decrease the contraction of smooth muscle. The purpose of our study was to determine if verapamil has a similar effect on the resting lower esophageal sphincter pressure in normal subjects and in patients with achalasia. Esophageal manometry was performed using a continuously perfused catheter assembly. Infusion of verapamil (0.15 mg/kg) over a 2-min period resulted in a statistically significant decrease in resting lower esophageal sphincter pressure in both normal subjects (n = 8) and patients with achalasia (n = 7) within 10 min postinfusion. This study suggests that verapamil may have potential as a drug therapy in treating the clinical symptoms of achalasia and diffuse esophageal spasm.     

Esophageal and Lower Response to Balloon Distention in Patients with Achalasia Esophageal Sphincter

Achalasia is characterized by absent orincomplete lower esophageal sphincter (LES) relaxationand aperistalsis in the smooth muscle esophageal body inresponse to swallowing. The esophageal and LES response to distention has not previously been studied.I aimed to characterize the responses to esophagealballoon distention in achalasia patients in comparisonto controls. Sixteen consecutive achalasia patients and 11 healthy volunteers underwent standardesophageal manometry followed by graded midesophagealballoon distention during which LES (as measured by theDent sleeve) and esophageal body pressures were monitored. Subject perception of distention wasalso recorded using a standardized scoring system. TheLES relaxation response to esophageal balloon distentionwas markedly impaired in achalasia patients, irrespective of whether the patient hadradiological evidence of a dilated or nondilatedesophagus. However, phasic contractions proximal to thedistending balloon were preserved. The esophageal bodyresponses below the balloon were inconsistent in bothgroups, and not significantly different from oneanother. Pain-sensation scores were significantly lowerin achalasia patients at the highest distending volumes, but this difference was attributable to thesubgroup of patients with a dilated esophagus.Distention-induced LES relaxation is markedly impairedin achalasia patients in keeping with loss of intrinsic inhibitory innervation. Preservation of theproximal excitation suggests that extrinsic vagalreflexes are intact.     

Isolated Lower Esophageal Sphincter Relaxation as ``Wave-Suppressed' Secondary Peristalsis

Esophageal venting following air insufflation may occur by secondary peristalsis or by isolated transient lower esophageal sphincter relaxation (TLESR). To identify factors determining venting by these two mechanisms, we analyzed the responses to esophageal air insufflation in 4 infants and in 2 adults. We used a nine-lumen dual-Dent-sleeve manometric catheter with an air insufflation esophageal side hole, identifying swallowing by pharyngeal manometry or submental electromyography. The time from the venting lower esophageal sphincter relaxation (whether part of a secondary peristalsis or an isolated TLESR) to the next swallow (whether spontaneous, in the infants, or on command, in the adults) was characterized as ≥15 sec or <15 sec. Of the 25 evaluable trials, the subsequent swallow was ≥15 sec after the venting response in 9 instances and <15 sec afterward in 16 instances. Eight of the 9 trials with delayed swallows (≥15 sec) were vented by secondary peristalsis, whereas 11 of the 16 with early swallows (<15 sec) were vented by TLESR (X² p < 0.01). TLESRs may be induced by esophageal stimuli, in which case they may represent ``wave-suppressed' secondary peristaltic complexes.     

Studies on the Mechanism of the Lower Esophageal Sphincter Pressure Response to Alkali Ingestion in Humans

To clarify the lower esophageal sphincter (LES) pressure response to alkali ingestion, normal subjects and postantrectomy patients with either a gastroduodenostomy or gastrojejunostomy were studied in a double-blind controlled fashion. LES pressure and serum gastrin concentrations were measured after ingestion of a 100 ml bolus of either 0.4 M NaHCO3 or 0.4 M NaCl. In addition, the effect of a therapeutic dose (30 ml) of a commercial antacid preparation was studied in a double-blind fashion in 14 patients with gastroesophageal reflux disease. Peak increases in LES pressure above basal were significantly higher (p less than 0.05) after NaHCO3 than after NaCl in normal subjects and in patients with vagotomy and Billroth I antrectomy, but not in patients with vagotomy and Billroth II antrectomy. Serum gastrin concentrations were unaffected by alkali. Thirty milliliters of liquid antacid containing aluminum and magnesium hydroxide resulted in a small sustained rise in LES pressure over the first 50 min after ingestion, but this was not statistically different than the placebo response. It is suggested that: 1) neither the antrum nor intact vagi nor gastrin were required for NaHCO3 ingestion to increase LES pressure; 2) the increase in LES pressure with NaHCO3 ingestion appears to rely upon an intact duodenum and may relate to volume and osmolarity of the alkali load; and 3) therapeutic doses of a liquid commercial antacid does not significantly increase LES pressure in the presence of an intact stomach.     

Transient Lower Esophageal Sphincter Relaxations and Esophageal Body Muscular Contractile Response in Reflux Esophagitis

In patients with gastroesophageal reflux disease (GERD), transient lower esophageal sphincter relaxations (TLESRs) are more frequently accompanied by acid reflux than in normals. The role of esophageal tone during gastroesophageal reflux events is unknown. We studied the tonic motor activity in the body of the esophagus during TLESRs with and without acid reflux in 11 patients with erosive esophagitis and compared the results with those previously obtained in healthy subjects. Esophageal peristaltic contractions were recorded 13, 8, and 3 cm above a sleeve that measured LES pressure. An intraluminal balloon was inflated 8 cm above the sleeve to induce an esophageal tonic contraction [artificial high pressure zone (HPZ)]. The percentage of TLESRs with acid reflux was significantly higher in patients with esophagitis than in healthy controls (58.3% vs 37.3%, P < 0.05). TLESRs per se were not associated with an inhibition or increase in esophageal body contractility, which, however, changed substantially immediately after reflux. In patients with esophagitis the esophageal body tonic contractility was inhibited in 59.5% of TLESRs vs 36% in controls (P < 0.05). Esophageal contractions during TLESRs traveled down the esophagus in 77% of the instances in patients vs 96.5% in controls (P < 0.05). In conclusion, gastroesophageal reflux during TLESRs was more frequently associated with inhibition of esophageal body tonic contractility in patients with esophagitis than in normals. The different response of the esophageal body to reflux observed in GERD patients may partially contribute to the higher prevalence of reflux during TLESRs in these patients.     

Effect of Somatostatin on Lower Esophageal Sphincter Characteristics in Man

Background: Data from previous studies on intestinal metaplasia at the gastroesophageal junction have been conflicting, which makes the diagnosis of Barrett's esophagus less obvious. This may partly be due to the lack of a reliable classification of the Z-line appearance. We previously proposed such a classification (the ZAP classification) that was shown to correlate with the prevalence of intestinal metaplasia. The use of different immunohistochemical techniques has increased in the study of intestinal metaplasia. In the present study our aim was to 1) evaluate the impact of different antibodies, namely cytokeratin (CK) 7, 13, and 20, CaCO3/73, and FBB2/29, in order to differentiate between Barrett's esophagus and cardia intestinal metaplasia, and 2) explore the staining patterns in different ZAP grades. Methods: Thirty-nine specimens with intestinal metaplasia were compared - 9 from Barrett's esophagus, 6 from cardia, and 24 from the Z-line. The Z-line specimens were evaluated with respect to ZAP grade. Results: No differences were encountered regarding staining patterns for CK13 and CaCO3/73 in Barrett's esophagus and cardia. The staining pattern of CK7/20 was significantly different between Barrett's esophagus and cardia. CK7/20 showed a rising frequency of Barrett's esophagus staining pattern with rising ZAP grade. Conclusion: CK7/20 is a feasible marker for Barrett's esophagus. Intestinal metaplasia in different ZAP grades differs regarding expression of immunohistochemical markers.     

Premature Lower Esophageal Sphincter Closure as a Cause of Dysphagia

Impaired lower esophageal sphincter (LES) relaxation is highly correlated with dysphagia. A variation of the impaired relaxation of the LES of achalasia has been described, characterized by premature closure after normal relaxation. With a microtransducer system, standard manometric testing followed by food ingestion identified 33 patients (12 male, 21 female, 18–79 yr old) who exhibited premature LES closure. Twenty-three (70%) of these patients had a presenting complaint of dysphagia. Of these, seven (30%) experienced dysphagia during food ingestion. Manometry documented a concurrent motor abnormality in the esophageal body in 28 (85%) patients. Of the five remaining patients who did not have a concurrent motor abnormality, all had a presenting complaint of dysphagia, and three (60%) experienced dysphagia during food ingestion. The incidence of dysphagia during testing reported by patients with premature LES closure is comparable to that reported by patients with achalasia (45%) or diffuse esophageal spasm (38%) who have been studied during food ingestion in our laboratory.