Reverse-perfused sleeve: an improved device for measurement of sphincteric function of the crural diaphragm

The sphincteric function of the crural diaphragm has been difficult to measure in humans. The authors recently reported the use of a Dent sleeve device to measure esophagogastric junction pressure during contraction of the crural diaphragm. However, the major limitation of the conventional sleeve device is its slow response rate, and sustained diaphragmatic contractions of 6-8 seconds must be induced to measure the true pressure. In this article, the principles of a reverse-perfused sleeve device and the theoretical basis for its fast response rate are reported. The reverse-perfused sleeve is validated in an in vitro model of the lower esophageal sphincter. Furthermore, in vivo studies were performed in seven healthy human subjects. Standardized Muller maneuvers and straight-leg raises were performed to induce diaphragmatic contractions. Pressure increases of 50-150 mm Hg during diaphragmatic contractions were attained in less than 1 second. The delay between the actual contraction of the diaphragm as measured by simultaneously recorded crural diaphragm electromyography and pressure recorded by the sleeve was only 0.25-0.50 seconds. Increasing the rate of infusion of the sleeve from 0.5 to 1.0 mL/min did not further improve the response rate of the reverse perfused sleeve. It was concluded that the reverse-perfused sleeve is a considerable improvement over the conventional sleeve for quantitating the sphincteric function of the crural diaphragm. The role of the crural diaphragm in reflux esophagitis may be easily investigated using a reverse-perfused sleeve device.     

Esophageal manometry

Pressure transients in the pharyngoesophagus vary widely, from about 2500 mm Hg/sec in the pharynx to 150 mm Hg/sec in the lower esophageal sphincter (LES). Perfused side-hole and Dent-sleeve manometry have limitations with respect to their inability to record pharyngeal pressure transients and their relative inability to record abrupt pressure increases in the upper esophageal sphincter (UES), although falling pressure changes, ie, relaxations, of more than 1000 mm Hg/sec can be detected easily by the Dent sleeve. Hence, accurate pharyngeal and UES recordings require pressure sensors that are able to record pressure transients faster than 2500 mm Hg/sec. Microtransducers meet this requirement. Except for their relatively high costs of acquisition, microtransducers have a lot of advantages in comparison with the perfused side-hole methods: the small outer diameter and flexibility enable easy intubation; baseline pressures are not affected by subject position; and plumbing necessary for infusion is eliminated. After presoaking in water, calibration is stable and the baseline drift is acceptable. They have an excellent linearity and a negligible hysteresis. Their durability is satisfactory. The microtransducer assemblies can be designed in almost any configuration and even circumferentially sensitive microtransducers for acute sphincter measurements have been developed. For long-interval recordings of the UES and the LES, however, microtransducers are not suitable: for these the Dent sleeve is required. Recently, microtransducers have been used more frequently because they are indispensable in the 24-hr ambulatory esophageal manometry technology.     

Improved lower esophageal sphincter manometry: application of the end-hole recording technique in vivo

The recommendation to use a thin end-hole catheter for lower esophageal (LES) manometry has a strong theoretic background supported by previous in vitro studies. The pressure in the closed sphincter is measured, and the problem of pressure asymmetry eliminated. In this study the advantage and applicability of an end-hole catheter compared with the composite side-hole catheter for LES manometry was tested in vivo in dogs and human subjects. Pull-through manometry was performed with a continuously infused composite four-lumen catheter with one central channel and three side-hole channels enabling simultaneous end-hole and side-hole recording of LES pressure. A pull-through produced one end-hole and three side-hole pressure registrations. The end-hole recorded resting sphincter pressure was 19.7 +/- 4.5 cm H2O in 6 dogs and 9.9 +/- 6.8 cm H2O in 89 human subjects (volunteers and patients). The side holes recorded higher pressures, longer high-pressure zones, and obvious differences--asymmetry--between the three channels. The correlation between the side-hole and end-hole recordings was equally poor with regard to both pressure and length, with r values from 0.48 to 0.61. The relative difference between the end hole and side holes was most pronounced in low-pressure sphincters. In the dogs the end-hole and one side-hole channel always recorded LES pressure close to the expected 0 pressure during reflux, whereas the other two side-hole channels recorded high pressures. The present study proved the applicability of the end-hole technique for LES manometry in vivo in man. The end hole seemed to record true sphincter pressure.     

Current concepts of the antireflux barrier

The lower esophageal sphincter, crural diaphragm, and phrenoesophageal ligament are the anatomic structures that constitute the antireflux barrier. The intraluminal pressure at the esophagogastric junction (EGJ) reflects the strength of the antireflux barrier. The end-expiratory pressure is a result of the tonic activity of the smooth muscles of the lower esophageal sphincter. The EGJ pressure increases during inspiration owing to the effect of the crural diaphragm. There is a reflex increase in the EGJ pressure during periods of increased intra-abdominal pressure, and the crural diaphragm contributes to this reflex contraction of the EGJ. Based on the contribution of the lower esophageal sphincter and crural diaphragm to the EGJ pressure, a two sphincter hypothesis of the antireflux barrier competence is suggested.     

Use of Simultaneous High-Resolution Endoluminal Sonography (HRES) and Manometry to Characterize High Pressure Zone of Distal Esophagus

The purpose of this investigation was to separate the high pressure zone (HPZ) of the distal esophagus into its two components, the intrinsic lower esophageal sphincter (LES) and the extrinsic crural diaphragm (CD), using simultaneous esophageal manometry and high-resolution endoluminal sonography. Five normal subjects were studied during end inspiration using a dual manometry/ultrasound catheter. The HPZ in the distal esophagus was characterized ultrasonographically as the CD distally and as an overlap of CD and LES proximally. In four of five volunteers, the initial distal rise in pressure at the HPZ corresponded to imaging of CD rather than imaging of the LES. In all subjects, peak pressure corresponded to an overlap of CD and LES. In conclusion, it is possible to divide the HPZ into its two components, the LES and CD using simultaneous high-resolution endoluminal sonography and esophageal manometry. During end inspiration, the CD contributes to the initial distal rise in pressure at the HPZ. Peak pressure of the HPZ corresponds to an overlap of the LES with the CD.     

Role of the diaphragm in the genesis of lower esophageal sphincter pressure in the cat

To determine the role of the diaphragm in the genesis of the high-pressure zone at the lower esophageal sphincter (LES) we studied the effect of diaphragmatic contraction on lower esophageal sphincter pressure in 10 anesthetized adult cats. Despite anchoring the pressure recording assembly within the LES to prevent axial movement of the sphincter during respiration relative to the pressure recording ports, there was an average oscillation in LES pressure of 17.4 +/- 5.5 mmHg, the frequency of which was the same as the respiratory rate. Peak LES pressure occurred at end-inspiration corresponding with peak diaphragmatic electromyogram. During periods of central apnea induced by manual hyperventilation there was absence of both diaphragmatic electromyogram and the oscillations in LES pressure. Lower esophageal sphincter pressure during apnea was equal to end-expiratory pressure during spontaneous respiration. Following complete neuromuscular blockade with pancuronium, artificial respiration with increasing tidal volumes resulted in increasing oscillations in pressure. However, the magnitude of the pressure oscillation even at tidal volumes four times normal was always significantly below that observed during spontaneous eupnic respiration. Furthermore, progressive augmentation of diaphragmatic electromyogram activity by breathing 5% CO2 in air revealed a linear correlation between the magnitude of the respiratory-induced pressure oscillations of the LES and peak integrated diaphragmatic electromyogram in individual animals. It is concluded, therefore, that (a) intrinsic LES tone is best approximated by end-expiratory pressure during spontaneous respiration, (b) the respiratory-induced oscillations in LES pressure are primarily the result of active diaphragmatic contraction, and (c) the level of diaphragmatic electrical activity directly influences the magnitude of the pressure oscillation.     

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 somatostatin on lower esophageal sphincter characteristics in man

BACKGROUND: Somatostatin (SST) is known for its inhibitory effect on the gastrointestinal tract. Transient lower esophageal sphincter relaxations (TLESR), low or absent LES pressure (LESP) and swallow-induced LES relaxations are the most important reflux mechanisms. METHODS: We have studied the effect of somatostatin on lower esophageal sphincter (LES) characteristics in man. Nine healthy volunteers participated in four experiments performed in random order and double-blind during continuous infusion of somatostatin (250 microg/h) or saline (control) under fasting and postprandial conditions. Esophageal motility was measured with sleeve manometry combined with pH metry. RESULTS: Under fasting conditions LESP was not influenced by somatostatin. Ingestion of the carbohydrate meal significantly (P < 0.01) decreased LESP. During continuous somatostatin infusion the postprandial decrease in LESP did not occur; LESP was even significantly (P < 0.05) increased over basal levels. Somatostatin did not significantly influence TLESR frequency, neither under basal conditions, nor postprandially. The residual pressure during swallow-induced LES relaxation was significantly (P < 0.05) increased by somatostatin. CONCLUSION: In humans somatostatin prevents postprandial reduction in LESP, does not affect TLESR, but inhibits swallow-induced LES relaxation.     

Lower esophageal sphincter pressure in normal individuals and patients with gastroesophageal reflux. A comparison between end-hole and side-hole recording techniques

The advantage of a single-lumen end-hole catheter compared with the usual composite side-hole catheter for lower esophageal sphincter (LES) manometry has been studied in vitro and in vivo. In the present study LES pull-through manometry was performed with a special catheter, enabling simultaneous end-hole and side-hole recording of LES pressure. Eighteen normal individuals with normal 24-h pH-monitoring (control group) and 42 reflux patients with pathologic 24-h pH-monitoring (reflux group) were studied. End-hole recorded resting sphincter pressure (RSP) in the control group was 15.4 +/- 5.0 cm H2O and in the reflux group 6.4 +/- 6.4 (p less than 0.0005). Side-hole recorded RSP (mean S1-S3) was 20.8 +/- 11.6 and 11.9 +/- 6.8, respectively (p less than 0.005). End-hole recorded total sphincter length (SL) in the control group was 34 +/- 9 mm and in the reflux group 27 +/- 12 (p less than 0.025) and abdominal sphincter length (ASL) 23 +/- 7 and 16 +/- 9, respectively (p less than 0.005). Side-hole recorded SL was 30 +/- 7 and 30 +/- 12, respectively (NS) and ASL 22 +/- 6 and 18 +/- 9 respectively (NS). After intake of 500 ml of water both LES pressure and length decreased in both groups but the separation between the groups was neither improved nor impaired. The results support the view that LES insufficiency is an important cause of gastroesophageal reflux. That LES had a lower pressure and was shorter in patients with reflux was best demonstrated by end-hole recorded pressure.     

Effect of phenylalanine-vasopressin on the lower esophageal sphincter. Possible implications in the treatment of bleeding esophageal varices]

Vasopressin and its analogs are used inthe treatment of bleeding esophageal varices. Since gastrointestinal reflux may have a deleterious effect on variceal hemorrhage, the effect of 2,3-phenylalanine-8-lysine-vasopressin upon the lower esophageal sphincter (LES) was studies by rapid pull-through manometry in 24 persons. PLV infusion up to a dosis of 2.7 mU/kg/h raised LES pressure from 15.1 +/- 1.3 (SEM) to 17.9 +/- 2.0 mm Hg. Higher doses lowered LES pressure progressively to 12.1 +/- 0.7 mmHg at 54 mU/kg/h. The serum gastrin level did neither correlate with basal LES pressure not with LES pressure changes during PLV infusion. Therefore, PLV does not appear to act indirectly through serum gastrin. Because of the danger of systemic side effects and of the undesirable in LES pressure with the usual high doses of vasoactive substances, a continuous infusion of lower doses of vasopressin analogs appears to be advantageous.     

Comparison of Air-Coupled Balloon Esophageal and Anorectal Manometry Catheters with Solid-State Esophageal Manometry and Water-Perfused Anorectal Manometry Catheters

Clinical gastrointestinal manometry studies are currently performed with multilumen water-perfused polyvinyl or strain gauge sensor solid-state catheters. A disposable catheter incorporating air-filled balloons has been developed with performance characteristics suitable for esophageal and anorectal manometry studies. Our aim was to compare esophageal and anorectal pressure measurements using this newly developed catheter with measurements obtained using standard solid-state or water-perfused catheters. Measurements of resting LES pressure, esophageal contraction amplitudes, and anorectal rest and squeeze pressures were obtained in 10 healthy volunteers using a solid-state esophageal catheter, a water-perfused anorectal catheter, and air-filled balloon esophageal and anorectal catheters. Correlation coefficient analysis demonstrated that LES pressures, esophageal contraction amplitudes, and anorectal resting and squeeze pressures were not significantly among between the different catheters. We conclude that recently developed air-filled balloon esophageal and anorectal manometry catheters provide very similar measurements of LES, esophageal body, and anorectal sphincter pressures compared to presently used manometry catheters.     

Correlation between esophageal contraction amplitude and lower esophageal sphincter pressure in patients with nutcracker esophagus

Nutcracker esophagus (NE) is a primary esophageal motility disorder characterized by high-wave amplitude at the distal esophagus. The aim of this study was to analyze patients with NE and determine the relationship between distal esophageal contraction amplitude and lower esophageal sphincter (LES) pressure. Esophageal manometry tracings of patients with NE, defined as the presence of distal contraction amplitude of more than 182 mmHg after wet swallow, were analyzed. LES pressure was measured as the mean end-expiratory value. Spearman's correlation coefficient analysis was used to compare esophageal contraction amplitude with LES pressure. This comparison was also performed in patients with isolated hypertensive LES (HLES) and in subjects with normal manometry. Forty patients (25 female, 15 male; mean age 54 years) with NE were included in the study. Mean (SD) distal esophageal contraction amplitude was 230 (35.7) mmHg and mean LES pressure was 27.3 (5.7) mmHg. Esophageal contraction amplitude showed a positive correlation with LES pressure (r = 0.49, P < 0.01). In contrast, no correlation was found in patients with HLES (r = 0.21, P > 0.05) and in those with a normal manometric study (r = 0.18, P > 0.05). It is concluded that in patients with nutcracker esophagus a positive correlation exists between distal esophageal contraction amplitude and LES pressure, suggesting a diffuse hypertensive pattern involving smooth muscle at the distal esophagus and adjacent LES.     

Transient lower esophageal sphincter relaxations and reflux: mechanistic analysis using concurrent fluoroscopy and high-resolution manometry

BACKGROUND & AIMS: The aim of this study was to perform a detailed analysis of the mechanics leading to esophagogastric junction (EGJ) opening during transient lower esophageal sphincter relaxations (tLESRs) using high-resolution manometry coupled with simultaneous fluoroscopy. METHODS: Six subjects without hiatus hernia had endoclips placed at the squamocolumnar junction and 10 cm proximal. A 36-channel solid-state manometric assembly was placed spanning from stomach to pharynx, and subjects were studied for 2 hours after a high-fat meal. An esophageal pH electrode also was placed and fluoroscopy was initiated at the onset of a tLESR. Axial clip movement was measured during replay of the videotaped fluoroscopy and was correlated with manometric data. RESULTS: Ninety-three tLESRs were recorded, 62 tLESRs of which had good fluoroscopic visualization. Seventy-eight tLESRs had manometric evidence of flow and the majority had evidence of a common cavity (88%), but few were detected by the pH electrode. Esophageal shortening and crural diaphragm inhibition always preceded EGJ opening and common cavity. A positive pressure gradient between the stomach and the EGJ lumen of 7.1 mm Hg (interquartile range, 4.1-9.1 mm Hg) preceded the EGJ opening. CONCLUSIONS: Key events leading to the EGJ opening during tLESRs were LES relaxation, crural diaphragm inhibition, esophageal shortening, and a positive pressure gradient between the stomach and the EGJ lumen. The manometric signature of opening was pressure equalization within the EGJ, but this only occasionally was associated with pH evidence of reflux. Future investigations will need to analyze how this delicately balanced anatomic-physiologic system is perturbed in subjects with reflux disease.     

The effect of sildenafil on lower esophageal sphincter and body motility in normal male adults

OBJECTIVE: Sildenafil relaxes smooth muscle by blocking type 5 phosphodiesterase, which destroys nitric oxide-stimulated cyclic guanosine monophosphate. The aim of this study is to investigate the change of lower esophageal sphincter (LES) and body motility with the lapse of time after sildenafil infusion in normal male adults. METHODS: After basal esophageal manometry in eight healthy male adult volunteers, we infused a 50-mg tablet of sildenafil dissolved in water in the stomach through the manometry catheter and observed the changes of LES and body motility with the lapse of time. We randomized the study population into two groups, and esophageal manometry was repeated in LES and body sequence in four volunteers and in body and LES sequence in the other four volunteers immediately after sildenafil infusion. RESULTS: LES resting pressure significantly decreased after sildenafil infusion. The body peristaltic amplitude gradually decreased and eventually disappeared, and the latency increased significantly after sildenafil infusion in both the proximal and distal esophagus. CONCLUSIONS: These data support that nitric oxide mediates LES relaxation and the timing of esophageal peristalsis. In the future, sildenafil can be tried in some esophageal motor disorders, which have defects in nitric oxide neuromuscular communication.     

Lower esophageal sphincter relaxation characteristics using a sleeve sensor in clinical manometry

Objective: We undertook this study to determine the characteristics of swallow-induced lower esophageal sphincter (LES) relaxation in the setting of clinical manometry using a standardized methodology.
Methods: We reviewed 170 manometric recordings performed using a perfused manometric assembly with a sleeve sensor and a computer polygraph. Patients were categorized as patient controls, gastroesophageal reflux disease (GERD), diffuse esophageal spasm (DES), or achalasia. Tracing were semiautomatically analyzed for basal LES pressure, LES pressure during deglutitive relaxation (relaxation LES pressure), duration of LES relaxation, timing of LES relaxation, and the success rate of primary peristalsis.
Results: Forty-six patient controls, 93 with GERD, five with DES, and 26 with achalasia were identified. GERD and achalasia patients had lower or higher basal LES pressures than patient controls, respectively. Compared with patient controls, achalasia patients had higher relaxation LES pressures, lower percent LES relaxation, and shorter durations of LES relaxation. The best single measure for distinguishing achalasia was the relaxation LES pressure; using the 95th percentile value of patient controls (12 mm Hg) as the upper limit of normal, its sensitivity and positive predictive value for the diagnosis of achalasia were 92% and 88%, respectively. Coupled with the finding of aperistalsis, a relaxation LES pressure ≥10 mm Hg achieved 100% sensitivity and positive predictive value among these patients.
Conclusion: Sleeve sensor recording is a practical method for clinical manometry that reliably records LES relaxation characteristics and is amenable to both a standardized manometry protocol and a semiautomated analysis routine. Relaxation LES pressure has a high diagnostic value for achalasia.     

Effect of Doses of Glucagon Used to Treat Food Impaction on Esophageal Motor Function of Normal Subjects

We studied 10 normal subjects to determine the effect of doses of intravenous glucagon used to treat food impaction on esophageal motor function. With a multilumen assembly perfused by a low compliance pneumohydraulic infusion pump, esophageal manometry was performed during baseline and after randomized administration of 0.25, 0.5, and 1 mg intravenous glucagon. Mean proximal and distal amplitudes of contraction, proximal and distal amplitude of contraction duration, lower esophageal sphincter (LES) resting pressure, percentage of LES relaxation, and glucagon-related side effects were evaluated. No effect on proximal amplitude of contraction and proximal or distal esophageal contraction duration was noted. Mean amplitude of contraction in the distal esophagus was further reduced with increased dosage of glucagon but did not achieve statistical significance. Mean LES resting pressure was significantly reduced after 0.25 mg (18.7 ± 1.8 vs. 10.2 ± 1.5 mmHg, p= 0.0001) and further reduced after 0.5 mg (5.9 ± 1.2 mmHg, p= 0.0009). Mean LES relaxation was significantly reduced after 0.25 mg (93.1 ± 2.4% vs. 63.6 ± 8.8%, p= 0.0031). The 1-mg dose versus the 0.5-mg did not provide further reduction in any LES function parameters. One subject experienced transient nausea after 0.5 mg, and 4 subjects experienced nausea after 1 mg glucagon. In conclusion, increased doses of glucagon further reduce mean distal esophageal amplitude of contraction. Although maximum reduction in mean LES resting pressure was achieved with 0.5 mg, it did not provide any potential therapeutic advantage over 0.25 mg glucagon. Nausea is a common, transient side effect predominantly affecting subjects treated with the 1-mg dose.     

Influence of Esophageal Motility on Esophageal Speech of Laryngectomized Patients

After laryngectomy for treatment of cancer of the larynx, the patient may have vocal rehabilitation by esophageal speech. Some patients fail to achieve the esophageal speech due to reasons involving surgery, radiotherapy, and psychological alterations. Our hypothesis is that the esophageal motility alterations consequent to laryngectomy may be involved in the failure to achieve esophageal speech. Using manometry with continuous perfusion, we studied the esophageal motility of 25 laryngectomized patients, 10 of them able to produce esophageal speech and 15 unable to produce esophageal speech, and 40 asymptomatic normal volunteers. The lower esophageal sphincter (LES) pressure was measured by the rapid pull-through method and the upper esophageal sphincter (UES) pressure by the station pull-through method. The contractions were measured at 5, 10, and 15 cm above the LES after the subjects performed 10 swallows with a 5-mL bolus of water. By comparing volunteers and laryngectomized patients, we found a lower UES pressure, lower amplitude of contractions, and increased percentage of simultaneous contractions in laryngectomized patients (p <0.05). There was no difference between patients able and unable to produce esophageal speech in LES and UES pressure, esophageal contraction duration and velocity, or in the percentage of failed and simultaneous contractions. The esophageal contraction amplitude was lower in patients who acquired esophageal speech than in patients who did not (p <0.05 at 10 cm from LES). We conclude that there are esophageal motility alterations in laryngectomized patients but only the decrease of esophageal contraction amplitude seems to be associated with the acquisition of esophageal speech.     

High-resolution manometry of the EGJ: an analysis of crural diaphragm function in GERD

AIM: High-resolution manometry (HRM) provides a spatially enhanced, dynamic representation of the esophagogastric junction (EGJ) high-pressure zone making it possible to isolate the crural diaphragm (CD) contraction from expiratory lower esophageal sphincter (LES) pressure. This study compared CD function of subjects with and without gastroesophageal reflux disease (GERD). METHODS: A total of 75 asymptomatic controls and 156 GERD patients (EGD or pH monitoring positive) underwent HRM. The EGJ axial pressure profile was analyzed over five respiratory cycles to quantify the position and contractile vigor of the CD relative to the LES. Correlations between EGJ HRM attributes and GERD status were examined. RESULTS: GERD patients had significantly greater CD-LES separation compared with either controls or EGD-/pH- patients. GERD patients also had significantly less inspiratory augmentation of EGJ pressure (EGD-/pH+, 11.5 +/- 1.9 mmHg; EGD+, 10.0 +/- 1.2 mmHg) compared with controls (16.9 +/- 1 mmHg) or EGD-/pH- patients (16.7 +/- 0.2 mmHg). Using a logistic regression model that simultaneously examined expiratory LES pressure, LES-CD separation, and inspiratory EGJ augmentation while controlling for age and BMI, only inspiratory augmentation had a significant independent association with GERD. CONCLUSIONS: HRM characterization of EGJ morphology correlates with the objective demonstration of GERD. Although both LES pressure and LES-CD separation are associated with GERD, the strongest association and the only independent predictor of GERD as a categorical outcome in a logistic regression analysis was impaired CD function as indicated by reduced inspiratory augmentation of EGJ pressure.     

Depressant effect of sodium nitroprusside on the lower esophageal sphincter of the opossum.

In this study, we evaluated the effect of sodium nitroprusside (SNP), a vascular smooth-muscle relaxant, on lower esophageal sphincter (LES) pressure in the opossum. Resting LES pressure was monitored with a perfused sleeve sensor which allows accurate recording of LES pressure irrespective of axial LES motion. Intravenous pulse doses and infusion doses of SNP both caused significant decreases in both blood pressure and LES pressure. Les tone, however, was more sensitive to SNP than blood pressure. For example, an SNP pulse dose of 20 microgram/kg which lowered blood pressure only about 30% virtually abolished LES tone. A similar result was obtained for an SNP infusion dose of 10 microgram/kg/min. Tachyphylaxis to SNP did not occur for repeated pulse doses to 10 microgram/kg, but did develop during a 20-min infusion of 10 microgram/kg/min. The effect of SNP on LES pressure was not antagonized by propranolol, metiamide, haloperidol, atropine, phentolamine, or tetrodotoxin. We conclude that the potent depressant effect of SNP on LES tone is due to a direct action of the drug on sphincter smooth muscle.     

Effects of Octreotide on Lower Esophageal Sphincter in Patients with Cirrhosis and Portal Hypertension

We investigated the effects of octreotide infusion on the contractile activity of the esophageal body and lower esophageal sphincter in cirrhotic patients with esophageal varices. Esophageal manometry was performed in 36 alcoholic cirrhotic patients. They were randomly allocated to three groups and received the following treatments blindly for 90 min: an initial 100-g intravenous bolus followed by a continuous 25 g/hr octreotide infusion (group I, N = 13), a continuous 25 g/hr octreotide infusion without an initial bolus (group II, N = 13), and a continuous placebo infusion (group III, N = 10). Before drug infusion, mean lower esophageal sphincter pressure and mean esophageal body contraction pressure and duration were similar in the three groups. Compared to the placebo group, lower esophageal sphincter pressure increased significantly in groups I and II, 30 min (30%, 22%, 3% respectively; P = 0.006), 60 min (44%, 35%, 0.6%; P = 0.0002), and 90 min (67%, 41%, 2.5%; P = 0.0001) after octreotide infusion, as did esophageal body contraction pressure and duration. We conclude that octreotide has a potent effect on LES tone in cirrhotic patients.