Basal Lower Esophageal Sphincter Pressure Research Articles

Somatostatin effects on lower esophageal sphincter function.

The effect of somatostatin (GH-RIH) infusion (2 microgram/min) on lower esophageal sphincter pressure (LESP) responses to various stimuli was evaluated in adult male baboons. GH-RIH infusion did not affect basal LESP, but did cause a significant suppression of mean immunoreactive insulin (IRI) to 5.8% of basal values (P less than 0.05). Pentagastrin IV caused dose-related increases in LESP that were unaffected by GH-RIH. Abdominal compression caused a threefold rise in LESP (P less than 0.005) both without and with GH-RIH. However, atropine (20 microgram/kg iv bolus) completely blocked this cholinergic LES pressure response. Intragastric alkali as well as intragastric glycine caused significant increases in LESP (P less than 0.05). These LESP responses to alkali and to glycine were totally abolished by GH-RIH. In conclusion, GH-RIH infusion in the baboon does not affect basal LESP, LES smooth muscle response to exogenous stimulation, nor a cholinergically mediated LES response. GH-RIH does inhibit the response of LESP both to intragastric alkali and to glycine by the apparent suppression of a hormonally mediated mechanism.

Gastroesophageal reflux among severely retardedchildren

Of 136 institutionalized severely retarded children, 20 (15%) had recurrent vomiting. Of these 20, 15 had gastroesophageal reflux diagnosed by x-ray examination, acid reflux text, or both. Esophagitis was noted by endoscopy in ten of 14 patients with GER. Four patients were anemic and six had had one or more episodes of aspiration pneumonia in the 12 months prior to study. Reduced basal lower esophageal sphincter pressure was the most common manometric abnormality noted in the patients with GER. Responses of the LES to bethanechol and swallow were normal, as was the basal pressure of the upper esophageal sphincter. Abnormal propagation of esophageal peristalsis was seen in six patients, all of whom had moderate or severe esophagitis. When compared to the nonvomiting retarded patients, the GER patients had significantly lower mental age and higher incidence of scoliosis. Patients with GER who had basal LES pressure less than 10 mm Hg did not improve with medical management. Recurrent vomiting is a common and serious problem in severely retarded children, the organic cause of which can be demonstrated by the application of appropriate investigative techniques.

L-Dopa inhibits metoclopramide stimulation of the lower esophageal sphincter in man

Opossum lower esophageal sphincter smooth muscle contains inhibitory dopaminergic receptors. Since metoclopramide is a dopaminergic antagonist in many experimental situations, the present study was designed to investigate whether this mechanism could explain the lower esophageal sphincter (LES) stimulating action of metoclopramide in man. The interactions of (1) oral L-dopa, a dopamine precursor, and metoclopramide; and (2) L-dopa and the cholinergic agent, bethanechol, on lower esophageal sphincter pressure (LESP) in normal subjects were examined. Oral L-dopa significantly inhibited LESP response to either oral metoclopramide 20 mg (P less than 0.05), or intravenous metoclopramide 20 mg (P less than 0.05). In contrast, L-dopa did not inhibit the LESP response to subcutaneous bethanechol (0.07 mg/kg). Mean basal LESP measured 50 min after ingestion of 1000 mg L-dopa, 19.3 +/- 3.1 mm Hg, was significantly less than basal LESP after L-dopa placebo, 29.3 +/- 4 mm Hg (P less than 0.01). It is concluded that (1) L-dopa inhibited the metoclopramide-induced rise in LESP but not peak stimulation of LESP by bethanechol; (2) there is evidence for the possibility of LES dopaminergic inhibitory receptors in man; and (3) these data are consistent with the hypothesis that metoclopramide acts on the LES by blocking a dopaminergic pressure-lowering mechanism.

Sympathetic Control of Lower Esophageal Sphincter Function in the Cat

The purpose of this study was to determine the effect of direct stimulation of the sympathetic nerves on the lower esophageal sphincter (LES) in the anesthetized cat. Neither unilateral nor bilateral cervical sympathectomy, or splanchnicectomy significantly modified basal LES pressure in animals with intact vagi, or animals having undergone bilateral cervical vagotomy. Electrical stimulation of the cut, peripheral, cervical sympathetic trunk increased mean arterial blood pressure, but had no effect on LES pressure or LES relaxation as induced by vagal stimulation. Stimulation of the central end of the cervical sympathetic trunk had no effect on LES pressure. Stimulation of the central end of the cut splanchnic nerve produced a decrease in LES pressure with a maximal response of 69.1+/-16.0% (mean+/-SEM). This inhibitory response was not modified by either propranolol or bilateral cervical vagotomy. Stimulation of the peripheral end of the cut, greater splanchnic nerve gave an increase in LES pressure with a maximal response of 38.2+/-7.19 mm Hg. Guanethidine, in the presence or absence of the adrenal glands, significantly augmented this excitatory response. This response was also slightly increased by phentolamine alone at 10 V, 1 Hz, but was not altered by propranolol. The excitatory response was completely antagonized by atropine or by trimethaphan camsylate. Stimulation of the peripheral end of the splanchnic nerve inhibited LES relaxation as induced by vagal stimulation. The results of this study suggest that: (a) the LES in the cat is not affected by either central or peripheral stimulation of the cervical sympathetic trunk; (b) the central portion of the splanchnic nerve carries an afferent inhibitory response to the LES through yet unknown pathways; (c) the peripheral splanchnic nerve carries an atropine-sensitive excitatory response to the LES; and (d) the splanchnic nerves may modulate LES relaxation as induced by vagal stimulation.

Relationship Between Lower Esophageal Sphincter Pressure and Serum Gastrin Concentration in Zollinger-Ellison Syndrome and Other Clinical Settings

The relationship between lower esophageal sphincter (LES) pressure and serum gastrin concentration was examined in 16 normal subjects and in groups of patients with the following diagnoses: 17 with Zollinger-Ellison syndrome (ZES), 18 with gastroesophageal reflux, and 28 patients with previous operations for peptic ulcer disease, including 9 with vagotomy and pyloroplasty (V and P); 12 with vagotomy, subtotal gastrectomy, and gastroduodenostomy (Billroth I); and 7 with vagotomy, subtotal gastrectomy, and gastrojejunostomy (Billroth II). Mean (±SEM) basal LES pressure in ZES patients, 15.4 ± 1.2 mm Hg, was not significantly different from the mean LES pressure in normal subjects, 14.3 ± 1.2 mm Hg. Mean fasting serum gastrin concentration, however, in ZES patients, 2,034 ± 834 pg/ml, was significantly greater than that in normal subjects, 48.1 ± 4.7 pg/ml (P

Failure of atropine to inhibit gastrin-17 stimulation of the lower esophageal sphincter in man

Heptadecapeptide gastrin I (G-17) contracts the lower esophageal sphincter (LES) in man and animals. Previous studies in man found that atropine infusion (12 μg kg−1hr−1) inhibited the effect of gastrin on the LES, suggesting that this effect of gastrin is mediated by a cholinergic mechanism. Studies in the opossum have not shown similar inhibition. To reevaluate the interaction of atropine and G-17 on the LES, 6 normal males were studied. Submaximal and maximal effective doses of G-17 were used with both atropine infusion (12 μg kg−1hr−1) and rapid intravenous injection (1 mg). There was a small decrease in basal LES pressure with atropine infusion. However, neither atropine infusion nor rapid intravenous injection inhibited LES stimulation by submaximal and maximal doses of G-17. The results do not support the hypothesis that LES responses to gastrin are mediated by an atropine-sensitive cholinergic mechanism.

The measurement of resting and stimulated lower esophageal sphincter pressure using the rapid pull-through technique of esophageal manometry.

The value of the rapid pull-through technique of esophageal manometry for the measurement of lower esophageal sphincter pressure (LESP), in the diagnosis of symptomatic gastroesophageal reflux, has been investigated. The technique provides reproducible measurements of LESP in individual subjects during the period of a single recording study. It does not discriminate between normal subjects and patients with symptomatic gastroesophageal reflux in measurements of basal LESP or in measurements of the LESP response to abdominal compression and the cholinergic drugs bethanechol and metoclopramide. The findings of the study suggest that the rapid pull-through technique will not prove helpful in the diagnosis of symptomatic reflux.

Effects of Vasoactive Intestinal Peptide on Resting and Pentagastrin-Stimulated Lower Esophageal Sphincter Pressure

Vasoactive intestinal peptide (VIP) administered as an intravenous infusion at different doses (0.8, 1.6, and 3.2 micrograms per kg per hr, respectively) inhibited dose-dependently the response of the lower esophageal sphincter to an intravenous injection of pentagastrin (0.6 microgram per kg) in 4 healthy volunteers. Inhibition ranged from about 20% (not significant) with the low dose to about 55% (P less than 0.05) with the high dose. On the other hand, the VIP doses employed did not substantially decrease basal lower esophageal sphincter pressure. Calculated on the basis of plasma levels of the respective peptides, the inhibitory effect of VIP was about one-third of that of secretin. Even at the smallest dose of VIP, plasma levels of radioimmunoassayable VIP (20 to 100 pmoles per liter) markedly exceeded those encountered normally (1 to 19 pmoles per liter). So, the data presented do not support the suggestion that normally circulating VIP essentially contributes to the physiological regulation of the lower esophageal sphincter pressure; they do not exclude, however, such a role for locally released VIP.

Histaminergic pharmacology of primate lower esophageal sphincter.

We have studied the lower esophageal sphincter (LES) response to exogenous histamine and to H1- and H2-blocking agents in the awake baboon. Increasing intravenous bolus doses of histamine produce an increase in LES pressure with a maximum response at a dose of 12 microgram/kg. H1-receptor blockade with chlorpheniramine over a wide dose range did not alter basal LES pressure but did abolish the response of the LES to exogenous histamine. H2-receptor blockade with cimetidine at doses markedly inhibiting gastric acid secretion (2 mg/kg.h) did not alter basal LES pressure or the response of the LES to exogenous histamine. In addition, cimetidine did not alter the response of the LES to pentagastrin and bethanechol. Although histamine and histamine receptors are important in gastric secretion, they appear to have no identifiable role in the maintenance of basal LES smooth muscle tone in the baboon. These results demonstrate the presence of a stimulatory H1 receptor on baboon LES smooth muscle, but provide no evidence for the presence of an H2-inhibitory receptor. As opposed to the parietal cell, the LES response to pentagastrin and bethanechol does not require a H2 receptor.

Altered lower esophageal sphincter function during early pregnancy

To determine whether lower esophageal sphincter (LES) function was normal during early pregnancy, studies were performed in 8 pregnant women before and after abortion. Resting LES pressures were 22.1 ± 2.4 and 22.6 ± 2.3 mm Hg before and after abortion, respectively. During early pregnancy the LES pressure responses to pentagastrin were inhibited significantly. The LES responses to edrophonium and methacholine were decreased also. Finally, LES pressure responses to a protein meal were diminished in an additional 5 pregnant women. Serum concentrations of estrogen and progesterone were elevated during pregnancy, but the serum concentration of gastrin was unchanged. It can be concluded that in early pregnancy the basal LES pressure was within normal limits, but the LES pressure responses to hormonal, pharmacological and physiological stimulation were reduced (during demonstrated elevations of serum concentrations of estrogen and progesterone). These studies suggest that during early pregnancy, when no clinical symptoms of reflux are present, altered LES function may be demonstrated.

Effects of sodium nitroprusside and verapamil on the basal lower esophageal sphincter pressure

Effects of sodium nitroprusside and verapamil on the basal lower esophageal sphincter pressure

Effect of histamine and histamine antagonists on human lower esophageal sphincter function

The purpose of this study was to evaluate the effect of histamine phosphate and specific histamine antagonists on human lower esophageal sphincter (LES) pressure. Continuous intravenous infusions of histamine at doses of 2.0 to 40.0 μg/kg-hr gave graded increases in LES pressure with a peak response of 37.8 ± 4.6 mm Hg at 20.0 μg/ kr-hr. The LES response was not altered by an H1-antagonist, diphenhydramine (50 mg, intravenously), but was completely blocked by infusion of the H2-antagonist, cimetidine (4.0 mg/kg-hr). Also, oral cimetidine (300 mg) antagonized any increase in LES pressure during histamine infusion at a dose shown to give the maximal LES response. Despite this effect of cimetidine in antagonizing the maximal LES response to histamine, oral cimetidine at 200, 300, and 400 mg failed to alter basal LES pressure over a 3-hr period. Cimetidine also failed to alter the LES response to intravenous pentagastrin or oral beef hydrolysate. These studies suggest that: (1) human LES pressure increases in response to intravenous histamine phosphate through its action at an H2-receptor; (2) the H1-receptor has no apparent role in the human LES response to histamine; and (3) H2-antagonism with cimetidine has no effect on the human LES basal pressure or its response to gastrin stimulation.

Effect of cigarette smoking on the lower oesophageal sphincter.

Observations on the effect of smoking on lower oesophageal sphincter pressure (LOSP) are based on station pull-through techniques of eosophageal manometry and recent studies have suggested that these techniques are inaccurate. Reproducible measurements of LOSP may be achieved with a rapid pull-through (RPT) method of manometry. This method was used to determine the effect of cigarette smoking on LOSP in 10 asymptomatic volunteers and in a group of 10 patients with symptoms of gastro-oesophageal reflux. Basal LOSP measurements in the two groups were not significantly different but LOSP was reduced by 19% in asymptomatic subjects (p less than 0-01) and by 21% in symptomatic patients (p less than 0-02) during cigarette smoking. The results suggest that smoking should be avoided in the clinical management of gastro-oesophageal reflux.

Basal and Calcium-Stimulated Gastroesophageal Sphincter Pressure in Patients with Zollinger-Ellison Syndrome

Basal lower esophageal sphincter (LES) pressure was measured in 6 patients with the Zollinger-Ellison syndrome (ZES) and hypergastrinemia, and in 6 patients with duodenal ulcer and normogastrinemia. Basal LES pressure in ZES patients, 17.0 +/- 3.7 (mean +/- SE) mm Hg was similar to basal LES pressure in duodenal ulcer patients, 18.3 +/- 3.5 mm Hg (P greater than 0.10). LES pressure and serum gastrin concentration were not related in the ZES patients, r = 0.03, or in the duodenal ulcer patients, r = 0.20. Intravenous infusion of calcium gluconate in ZES patients produced a marked rise in serum gastrin concentration, delta = 1580 +/- 1110 pg per ml (P less than 0.001), and a moderate but significant rise in LES pressure, delta = 5.9 +/- 0.9 mm Hg (P less than 0.05). In duodenal ulcer patients calcium infusion produced only slight rises in gastrin concentration, delta = 10 +/- 12 pg per ml, and LES pressure, delta = 2.1 +/- 0.5 mm Hg, which were not significant (P greater than 0.10). This study suggests that basal LES pressure is not regulated by blood gastrin levels in the ZES. We interpret the calcium infusion study to show that the LES pressure in patients with ZES may respond to acute changes in endogenous gastrin levels.

Lower Esophageal Sphincter Pressure in Cirrhotic Men with Ascites: Before and After Diuresis

Lower esophageal sphincter pressure (LESP) was measured in 10 biopsy-proved cirrhotics with esophageal varices and tense ascites before and after diuresis to evaluate of ascites might play in the development of variceal bleeding. In the 10 cirrhotic men studied, basal LESP was 30.9 +/- 1.7 mm Hg before and 22.7 +/- 1.3 mm Hg (P less than 0.01) after a diuresis which resulted in a mean 12-kg weight loss. LESP responses to abdominal compression were also evaluated. The change in LESP in response to a standard degree of abdominal compression was greater in the presence of ascites (8.5 +/- 0.4) than in its absence (6.3 +/- 0.4) (P less than 0.01). Basal gastric pH and fasting plasma gastrin concentrations did not differ during the two testing periods. Based on these data and the rarity with which cirrhotic patients with ascites complain of heartburn, it is concluded that reflux esophagitis caused by failure of the lower esophageal sphincter to remain competent is unlikely to be a significant etiological factor in the development of variceal bleeding.

Relationship of Cervical and Abdominal Vagal Activity to Lower Esophageal Sphincter Function

The purpose of this study was to compare the effects of electrical stimulation of the abdominal and cervical portions of the vagus on lower esophageal sphincter (LES) pressure in the anesthetized opossum. Unilateral or bilateral abdominal vagotomy gave no significant change in basal LES pressure or in the sphincteric response to swallowing. Electrical stimulation of the peripheral end of the sectioned cervical vagus gave a frequency-related decrease in LES pressure with a maximum reduction of 93.5 +/- 2.5% at 10 HZ, 10 V. Stimulation of the central end of the cervical vagus increased LES pressure, with a maximum response of 34.0 +/- 1.9 mm Hg. Neither peripheral nor central stimulation of the sectioned abdominal vagus had significant effect on LES pressure (P greater than 0.05). Additionally, LES relaxation in response to swallowing or cervical vagal stimulation was intact after bilateral abdominal vagotomy. These studies suggest that whereas the cervical portion of the vagus mediates inhibitory and excitatory changes in LES pressure, the abdominal vagus has no demonstrable role in the control of LES function.

The adverse effect of chocolate on lower esophageal sphincter pressure

Decreased lower esophageal sphincter (LES) pressure after ingestion of chocolate has been previously noted. We have further evaluated the effect of chocolate on the known ability of gastric alkalinization or bethanechol to increase LES tone. 9 normal subjects were studied using an infused open-tip recording system. Pressure was monitored for a 15-min basal period, and for 60 min after ingestion of 120 ml of chocolate syrup either alone or with the concurrent administration of commercial antacid, oral bethanechol, or subcutaneous bethanechol. After chocolate ingestion, mean basal LES pressure of 14.6 +/- 1.1 (+/-SEM) mm Hg decreased significantly (P less than 0.01) to 7.9 +/- 1.3 mm Hg. An identical LES response occurred when antacid was given with the chocolate dose. Oral bethanechol (25 mg) and chocolate together resulted in lesser decreases in LES pressure. Subcutaneous bethanechol (5 mg) and chocolate produced significant increases (P less than 0.05) in sphincter pressure, although of lesser magnitude than reported with bethanechol alone. These results indicate that the adverse effect of chocolate on the LES is not reversed by gastric alkalinization and suggest that bethanechol in sufficient dose may overcome chocolate-induced decreases in LES pressure.

Effect of continuous infusion of pentagastrin on lower esophageal sphincter pressure and gastric acid secretion in normal subjects.

Bolus injections of gastrin or pentagastrin (PG) cause a marked elevation in lower esophageal sphincter pressure (LESP), and it has been suggested that serum gastrin concentration is the main physiological and pathophysiological regulator of LESP. We evaluated this hypothesis by measuring LESP and gastric acid secretion simultaneously in normal subjects during continuous infusion of PG (0.004-12 mjg/kg per h), since continuous infusion of a hormone probably simulates physiological hormone release better than bolus injection. In groups of 8-13 subjects there was no statistically significant increase in average LESP with any of seven PG infusion rates. However, a bolus of PG superimposed on the continuous infusion of PG resulted in a 20-mm Hg increase in LESP. Examination of results in individual subjects suggested that PG by infusion might be stimulating LESP in some subjects and inhibiting it in others. Therefore, individual dose-response studies were performed in two normal subjects. These revealed that 0.9 mug/kg per h PG by infusion elevated LESP by 10-12 mm Hg. This dose of PG also elicited maximal rates of gastric acid secretion. In one of the subjects an infusion of PG calculated to give one-half maximal acid secretion (D50) elevated LESP by 8 mm Hg; in the other the PG-D50 for acid secretion had no effect on sphincter pressure. Infusion of smaller amounts of PG had no effect on LESP, even though gastric acid secretion was stimulated submaximally. Thus, the parietal cells are more sensitive than the lower esophageal sphincter to the effect of PG by infusion. We conclude that PG by continuous infusion elevates LESP to only a modest degree (compared with the contraction that occurs after bolus injections of PG) and that the contraction occurs only within a narrow dose range between the D50 and D100 for acid secretion. Higher doses cause transient relaxation of LESP. Additional studies showed that basal LESP varied between 16 and 71 mm Hg in two subjects studied on 29 separate occasions, but there was no correlation with basal acid secretion. This suggests that the wide day-to-day fluctuations in basal LESP are not due to changing concentrations of gastrin in serum. The results of these experiments cast doubt on the hypothesis that serum gastrin concentration is the major determinant of LESP.

Comparative Effects of Metoclopramide and Bethanechol on Lower Esophageal Sphincter Pressure in Reflux Patients

The effects of oral metoclopramide, 10 and 20 mg, bethanechol, 25 mg, and placebo on lower esophageal sphincter pressure (LESP) were studied in 15 men with symptoms of gastroesophageal reflux and basal LESP less than 11 mm Hg. Each drug produced a significant increase in LESP when compared to placebo. Metoclopramide, 20 mg, produced a greater increase than either metoclopramide, 10 mg, or bethanechol, 25 mg. Serum gastrin concentrations were not altered by any of the drugs. Side effects were unremarkable. The LESP increasing effect of metoclopramide might be useful in treatment of gastro-esophageal reflux.

The Adrenergic Control of Lower Esophageal Sphincter Function: Response to Beta2 Adrenergic Agonists

Lands and co-workers have demonstrated a significant degree of selectivity of action at the beta adrenergic receptors of different tissues (1-3). Two types of beta adrenergic receptors, beta1 and beta2, have been proposed. Beta adrenergic effects on the heart are mediated by beta: receptors while the effects on bronchial and vascular smooth muscle are mediated by beta2 receptors (4-6). Although several selective beta2 adrenergic agonists have been synthesized, there is little information on the nature of the beta adrenergic receptors of the gastrointestinal tract. We have recently demonstrated that the lower esophageal sphincter (LES) of the opossum, an animal with a smooth-muscle distal esophagus similar to man, showed a dose-related inhibitory response to beta adrenergic stimulation (7). The purpose of this study was to compare the LES inhibitory response of iso-proterenol, a beta adrenergic agonist with effects at both types of beta receptors, with the selective beta2 adrenergic agonists, salbutamol and carbuterol. Our aim is to determine whether a beta2 adrenergic agonist can be used to reduce basal LES pressure without significantly altering the blood pressure or heart rate. Methods. All studies were performed on the adult opossum, species Didelphis vir-giniana. Male and female animals weighing between 2.2 and 4.6 kg were anesthetized with 2.0% chloralose (3.0 cm3/kg). After successful anesthesia, a heparinized cannula was inserted into the femoral artery and connected to an external transducer (Statham Instruments, Inc., Oxnard, CA) for constant blood pressure monitoring. A similar cannula was inserted into the opposite femoral vein for drug administration. Patency of this cannula was maintained through a slow infusion of 0.9 % saline. Intraluminal pressures were measured through water-filled polyvinyl catheters, 1.4 mm i.d., connected to external transducers (Statham P23BB) with a linear external calibration of 0-250 mmHg.