Changes In Lower Esophageal Sphincter Pressure Research Articles

Different Effects of Aerobic Exercise and Diaphragmatic Breathing on Lower Esophageal Sphincter Pressure and Quality of Life in Patients with Reflux: A Comparative Study.

BACKGROUNDGastroesophageal reflux disease (GERD) is a worldwide disorder with an increasing prevalence. The quality of life (QOL) of the patients may be influenced by reflux disease. Diaphragmatic breathing (DB), as well as aerobic exercise (AE), may improve the symptoms of reflux disease, although it remains a controversial issue. The aim of this study was to compare the effects of AE and DB on QOL and lower esophageal sphincter (LES) pressure of patients with moderate to severe reflux. METHODS This was a case-control study that was conducted for 8 weeks among patients with moderate to severe GERD. The block randomization method was designed to randomize patients into three groups (AE, DB, and control) to achieve equal sample sizes. The control group received omeprazole 20 mg once daily. The other groups, in addition to omeprazole, received AE and DB. QOL and LES pressure were measured before and after the study by Questionary and Manometry method, respectively. RESULTS 75 patients were enrolled in this study. Positive effects of DB on LES pressure was approved (p = 0.001). DB had significantly more effects on QOL than aerobic exercise (p = 0.003). AE can significantly improve QOL in patients (p = 0.02) but no significant change in LES pressure (p = 0.38). There was no change in the control group for both variables.CONCLUSION AE had no effects on LES pressure but can improve QOL of the patients. DB had more effects on QOL than AE, so injured or disable patients with reflux who cannot do AE, can benefit from DB to improve their reflux symptoms.

State of Evidence in Minimally Invasive Management of Gastroesophageal Reflux: Findings of a Scoping Review

Endoscopic management of gastroesophageal reflux disease (GERD) is being employed increasingly. The aim of this scoping review was to assess the volume of available evidence on the benefits of endoscopic and minimally invasive surgical therapies for GERD. criteria were used to perform an extensive literature search of data regarding the reported benefit of endoscopic therapies in GERD. Randomized controlled studies were utilized when available; however, data from observational studies were also reviewed. A formal review of evidence was performed in 22 studies. Inclusion and exclusion criteria and study duration were noted and tabulated. Assessment of outcomes was based on symptoms and objective criteria reported by investigators. Reported outcomes for the interventions were tabulated under the heading of subjective (symptom scores, quality of life metrics, and change in proton pump inhibitor use) and objective metrics (pH parameters, endoscopic signs, and lower esophageal sphincter pressure changes). Adverse events were noted and tabulated. The majority of studies showed symptomatic and objective improvement of GERD with the device therapies. Adverse events were minimal. However, normalization of acid exposure occurred in about 50% of patients and, for some modalities, long-term durability is uncertain. This scoping review revealed that the endoluminal and minimally invasive surgical devices for GERD therapy are a promising alternative to proton pump inhibitor therapy. Their place in the treatment algorithm for GERD will be better defined when important clinical parameters, especially durability of effect, are better understood.

Long-Term Efficacy of Peroral Endoscopic Myotomy for Patients with Achalasia: Outcomes with a Median Follow-Up of 36Months.

This study aimed to evaluate the long-term efficacy of peroral endoscopic myotomy (POEM) for patients with achalasia. Prospective data collected from 115 patients (median age 45years; interquartile range 34-57) with achalasia who underwent POEM at the First Affiliated Hospital of ZheJiang Chinese Medical University with a median follow-up of 36months were retrospectively analyzed. The Eckardt score and lower esophageal sphincter pressure changes were analyzed, and the gastroesophageal reflux was observed. During the final follow-up, the mean Eckardt score reduced from 7.5 ± 1.9 preoperatively to 2.3 ± 1.4 after 1month of surgery (P < 0.001). Treatment success was observed in 91.3% [confidence interval (CI) 86.2-96.4], 90.3% (CI 84.8-95.8), 89.0% (CI 83.1-94.9), 83.7% (CI 75.7-91.7), and 80.1% (CI 69.7-90.5) of patients after 12, 24, 36, 48, and 60months, respectively. A total of 16 (13.9%) failures occurred. Four patients were nonresponders (failure within 3months), eight had an early recurrence (between 3months and 3years), and four had a late recurrence (after 3years). Further, 21 (20.6%) patients had symptoms of reflux during the two-year follow-up. Only one patient with symptomatic reflux was newly added during the subsequent three-year follow-up. Moreover, 71 (61.7%) patients underwent gastroscopy after POEM, and 13 (18.3%) patients were diagnosed with reflux esophagitis. POEM is safe and effective in treating achalasia and has a favorable long-term efficacy.

Novel partial 5HT3 agonist pumosetrag reduces acid reflux events in uninvestigated GERD patients after a standard refluxogenic meal: a randomized, double-blind, placebo-controlled pharmacodynamic study

Low basal lower esophageal sphincter (LES) pressure and transient LES relaxations are major causes of gastroesophageal reflux disease (GERD). Pumosetrag, a novel selective partial 5HT3 receptor agonist, showed a promising effect on reducing reflux events in health. We aimed to evaluate the effect of pumosetrag on changes in reflux episodes, lower esophageal sphincter pressure (LESP), and specific symptoms in patients with GERD receiving a refluxogenic meal. Patients with GERD, who developed heartburn and/or regurgitation after ingestion of a refluxogenic meal, were randomized to 1 of 3 dose levels of pumosetrag (0.2, 0.5, or 0.8mg) or placebo. Before and after 7days of treatment, patients underwent manometry, intraesophageal multichannel, intraluminal impedance and pH after a standard refluxogenic meal. A total of 223 patients with GERD [125 (56%) women, mean (SD) age=36 (12) years] were enrolled. No overall treatment effects were detected for the total number of reflux episodes (acidic and weakly acidic) (p>0.5); however, significant treatment effects (p<0.05) on the number of acid reflux episodes were observed with lower values on pumosetrag 0.2mg (10.8±1.1), 0.5mg (9.5±1.1), and 0.8mg (9.9±1.1) compared with placebo (13.3±1.1). Significant treatment effects (p<0.05) were also observed for the percentage of time pH was <4, with less time for pumosetrag at 0.5mg (10%) and 0.8mg (10%) compared with placebo (16%). In GERD, the partial 5HT3 agonist pumosetrag significantly reduced the rate of acid reflux events but did not result in a significant change in LESP or symptomatic improvement over a 1-week treatment period.

American Gastroenterological Association Institute Technical Review on the Management of Gastroesophageal Reflux Disease

American Gastroenterological Association Institute Technical Review on the Management of Gastroesophageal Reflux Disease

Dorsal motor nucleus of the vagus: a site for evoking simultaneous changes in crural diaphragm activity, lower esophageal sphincter pressure, and fundus tone

The sphincter mechanism at the esophagogastric junction includes smooth muscle of the lower esophagus and skeletal muscle of the crural diaphragm (CD). Smooth muscle is known to be under the control of the dorsal motor nucleus of the vagus (DMV), while central nervous system (CNS) control of the CD is unknown. The main purposes of our study were to determine the CNS site that controls the CD and whether simultaneous changes in lower esophageal sphincter (LES) pressure and CD activity occur when this site is activated. Experiments were performed on anesthetized male ferrets whose LES pressure, CD activity, and fundus tone were monitored. To activate DMV neurons, L-glutamate was microinjected unilaterally into the DMV at three areas: intermediate, rostral, and caudal. Stimulation of the intermediate DMV decreased CD activity (-4.8 +/- 0.1 bursts/min and -0.3 +/- 0.01 mV) and LES pressure (-13.2 +/- 2.0 mmHg; n = 9). Stimulation of this brain site also produced an increase in fundus tone. Stimulation of the rostral DMV elicited increases in the activity of all three target organs (n = 5). Stimulation of the caudal DMV had no effect on the CD but did decrease both LES pressure and fundus tone (n = 5). All changes in LES pressure, fundus tone, and some DMV-induced changes in CD activity (i.e., bursts/min) were prevented by ipsilateral vagotomy. Our data indicate that simultaneous changes in activity of esophagogastric sphincters and fundus tone occur from rostral and intermediate areas of the DMV and that these changes are largely mediated by efferent vagus nerves.

A Novel Partial 5HT3 Agonist DDP733 after a Standard Refluxogenic Meal Reduces Reflux Events: A Randomized, Double-Blind, Placebo-Controlled Pharmacodynamic Study

Purpose: Transient lower esophageal sphincter (LES) relaxations are the major cause of gastro-esophageal reflux. DDP733, a selective partial agonist at 5HT3 receptors, increases LES in experimental animal models. However, its effect on gastroesophageal reflux or LESP in humans is unknown. Aims: To evaluate the effect of DDP733 on reflux episodes in healthy volunteers receiving a refluxogenic meal, and to assess the safety and tolerability of DDP 733. Methods: A randomized, double-blind, placebo-controlled crossover study evaluated the pharmacodynamic effects of DDP733. Subjects were randomized on a 1:2:1 basis to one of three dose levels of DDP733 (0.5 mg, 0.8 mg, 1.4 mg), and randomized to the order of administration of placebo or active drug. Healthy subjects underwent manometry, and intraesophageal multichannel intraluminal impedance and pH after a standard refluxogenic meal. For evaluating the safety and tolerability of DDP733, each subject took drug or placebo (three times daily) for one week. A pooled analysis of variance, of the within subject deltas (placebo-drug) over all three dose groups with dose specific tests (α= 0.017) for no change were examined. Results: DDP733 0.5 mg significantly reduced the rate of reflux episodes after refluxogenic meal from 10.4 (±2.2) on placebo to 6.3 (±1.2) on drug over a 2 hour period. However, DDP733 0.8 mg and 1.4 mg had no significant effect on reducing the number of reflux episodes (table). Significant differences in LESP and the proportion of time pH was < 4 (placebo-drug) after a reflexogenic meal were not detected. No serious adverse events on DDP733 were reported. Conclusion: In healthy subjects, the partial 5HT3 agonist DDP733 at a dose of 0.5 mg significantly reduces the rate of reflux events, but did not result in a significant change in LES pressure at one hour post dosing.Table: Reflux events, post treatment mean LESP, and proportion time that time pH < 4 on drug or placebo (Mean ± SEM)

An endoscopically implantable device stimulates the lower esophageal sphincter on demand by remote control: a study using a canine model

Implantable microstimulators (IMS) have been used in a variety of medical conditions. Selective stimulation to increase lower esophageal sphincter (LES) pressure may be useful in the control of gastroesophageal reflux disease. We evaluated on-demand stimulation of the LES with an endoscopically implanted microstimulator. We performed acute experiments in three 30-kg dogs. After LES manometry, a 3.3 mm x 28 mm microstimulator (the Bion) was implanted into the LES. Manometry was repeated with and without IMS stimulation to record the changes in LES pressure. Stimulation amplitude was varied from 3 mA to 10 mA, with a fixed frequency of 20 Hz and a pulse width of 200 microsec. The mean LES pressures prior to IMS implantation in the three dogs were 13.0 mm Hg, 5.0 mm Hg, and 14.9 mm Hg. The mean pressures were not significantly changed by IMS placement. There were no documented changes in LES pressure when the amplitude of stimulation was less than 8 mA. After stimulation of the IMS at a setting of 10 mA in dogs 1 and 2 and at 8mA in dog 3, however, the resultant LES pressures were 62.1 mm Hg, 35.1 mm Hg, and 26.8 mm Hg respectively, more than three times higher than post-implantation baseline levels (P < 0.02). The LES pressure can be increased using an on-demand microstimulator. The implantation procedure is minimally invasive, represents a novel therapeutic approach to gastroesophageal reflux disease, and may have therapeutic potential for other gastrointestinal motility disorders.

Gastroesophageal Reflux in the Preterm Neonate

After completing this article, readers should be able to: 1. Describe the epidemiology and pathophysiology of gastroesophageal reflux (GER) in preterm neonates. 2. Delineate the associations of GER with apnea, chronic lung disease, behavior, and growth of preterm infants. 3. Review the investigations used to evaluate GER in preterm infants. 4. Describe nonpharmacologic and pharmacologic therapies for GER. Gastroesophageal reflux (GER) is a normal physiologic event occurring across the age spectrum. It may contribute to a variety of disorders, including esophagitis, feeding problems, and airway disease in all age groups. (1) A large number of symptoms and signs have been purported to be caused by GER despite a lack of data showing a clear association between a specific symptom and GER. In preterm infants, empiric therapy often is administered using agents of unproven efficacy and safety to treat symptoms that likely are unrelated to GER. In a survey on management practices for GER in preterm infants, common treatment strategies included positioning (98%) and slopes (96%), histamine 2 (H 2) receptor antagonists (100%), feed thickeners (98%), antacids (96%), prokinetics (79%), proton pump inhibitors (PPIs) (65%), and dopamine receptor antagonists (53%). (2)(3) The safety, efficacy, and appropriate dosing recommendations for most medical therapies remain uncertain in neonates. In this review, we attempt to summarize the current literature regarding physiology, pathophysiology, and diagnostic and management strategies for GER pertinent to the neonate, with an emphasis on the preterm infant. GER describes the retrograde movement of stomach contents (air or feeding, liquid or semisolid, acid or alkaline, enzymes or bile salts) into the esophagus. GER disease (GERD) occurs when GER causes symptoms or signs such as pain, poor weight gain, esophagitis, hematemesis, and airway symptoms, including apnea, aspiration, recurrent pneumonia, chronic lung disease (CLD), or large airway inflammation. However, any of these symptoms or signs …

Avaliação manométrica do esfíncter inferior do esôfago de coelhos submetidos a fundoplicatura total e parcial

OBJETIVO: Analisar o efeito das fundoplicaturas total e parcial sobre a pressão e comprimento do esfíncter inferior do esôfago (EIE). MÉTODOS: Foram estudados 30 coelhos machos da raça Norfolk. Os animais foram divididos em 3 grupos de 10, na dependência da operação[cirurgia] realizada. Grupo 1 (controle)-laparotomia mediana (LM) e dissecção da transição gastroesofágica; grupo 2- LM e fundoplicatura total, e grupo 3-LM e fundoplicatura parcial. Todos os animais foram submetidos à manometria esofágica (ME) segundo a técnica de tração intermitente da sonda e infusão contínua dos cateteres com água destilada. A ME foi realizada em dois momentos: M1 (pré-operatório) e M2 (pós-operatório), e permitiu a análise da pressão (mmHg) e comprimento (cm) do EIE. RESULTADOS: Nos animais do grupo 1 não foi observada alteração da pressão e comprimento do EIE. Naqueles do grupo 2 (fundoplicatura total) foi observado aumento da pressão (69,7%) e do comprimento (81,8%) do EIE. Nos coelhos do grupo 3 (fundoplicatura parcial) houve aumento da pressão (58%) e do comprimento (100%) do EIE. CONCLUSÕES: As fundoplicaturas total e parcial acarretam aumento da pressão e comprimento de EIE. O incremento da pressão e comprimento de EIE independe do tipo de fundoplicatura utilizada.

Lower esophageal sphincter monitoring with sphinctometer: in vitro and in vivo studies.

The sphinctometer is a solid-state device system for prolonged ambulatory recordings of the lower esophageal sphincter (LES) pressure. The aims of this study were to determine 1) the pressure sensitivity and the latency of sphinctometer responses in vitro, 2) if the sphinctometer can record transient LES relaxations (TLESR) in vivo, and 3) if the currently accepted criteria for TLESR are applicable to sphinctometer recordings. Different segments of the sphinctometer were positioned in a chamber at known pressures to assess the sphinctometer readings as well as the latency of the response. Ten healthy subjects were investigated with the use of a solid-state transducer sphinctometer assembly and a pH probe for 4 h. The LES pressure was analyzed during baseline periods, swallow-induced LES relaxations (SILESR), and LES relaxations associated with acid reflux episodes (pH <4) (presumed TLESRs). Our results showed that sphinctometer readings were linearly related to the chamber pressure and the length of the segment exposed to the pressure; however, the latter was considerably underestimated. We also found that sphinctometer segments of equal length but at different levels showed different pressure readings, the mean response time of sphinctometer was 0.25 s, and sphinctometer output was susceptible to temperature changes of the environment. In humans, only 25 of 45 episodes (64%) and 17 of 22 episodes (77%) were detected by the sphinctometer as being SILESRs and TLESRs, respectively. The pattern of the LES pressure during acid reflux events resembled classical TLESR. We concluded that the sphinctometer is a useful device for determining qualitative changes in LES pressure. However, its major limitations are pressure underestimation, different sensitivity of various segments, pressure drifts, and underscoring of LES relaxations.

Effect of amino acids on lower esophageal sphincter characteristics and gastroesophageal reflux in humans.

The effect of a commercially available mixed amino acids solution, when given either intravenously or intragastrically, on lower esophageal sphincter (LES) pressure, frequency of transient LES relaxations (TLESRs) and gastroesophageal reflux (GER) was investigated in six healthy volunteers. LES pressure and esophageal pH were simultaneously recorded on three separate occasions 1 hr before (basal) and 3 hr during intravenous or intragastric infusion of amino acids (250 mg protein/kg/hr) or saline (control). No significant changes in LES pressure were seen in the control experiment. Intravenous amino acids caused a rapid and sustained (P < 0.01) decrease in LES pressure whereas intragastric amino acids decreased LES pressure only gradually and temporarily (P < 0.01). In the three experiments no significant differences were observed in TLESR frequency, the number of GER episodes, the mechanism of reflux, or duration of acid exposure. In healthy subjects both intragastric and, especially, intravenous infusion of amino acids significantly decrease LES pressure but do not affect the frequency of TLESRs or GER episodes during a continuous liquid gastric load.

Esophago-sphincter inhibitory reflex: role in the deglutition mechanism and esophageal achalasia.

The effect of esophageal distension on the lower esophageal sphincter (LES) in 14 normal volunteers and 6 esophageal achalasia (EA) patients was studied. A balloon-tipped catheter was introduced into the LES and a second one into the esophagus. The pressure response of LES to balloon distension of the esophagus and pharyngoesophageal sphincter (PES) was recorded. In normal subjects, esophageal distension caused significant decrease of LES pressure; this reflex action was reproducible and was called "esophagosphincter inhibitory reflex" (ESIR). PES distension caused insignificant LES pressure changes (p > .05). Distension of the anesthetized esophagus or PES did not evoke LES pressure response. The ESIR was nonfatigable. In EA patients, the resting LES pressure was significantly higher than normal (p < .01). Upon esophageal distension, the LES pressure increased, while no response occurred with PES distension. There was paradox ESIR in EA with a resulting esophago-sphincter dyssynergia. To conclude, the ESIR seems to be of significance in esophageal motility disorders and may be incorporated as investigative tool in such conditions.

Identification of longitudinal muscle activity in opossum lower esophageal sphincter

The aim of this study was to characterize lower esophageal sphincter (LES) longitudinal muscle contraction during changes in LES pressure in opossums. LES pressure was used as a marker of LES circular muscle contraction. Longitudinal muscle contraction was measured by strain gauge transducers. For precise placement of the strain gauge on the LES, the high-pressure zone was identified using a manometric-laser illumination technique. Measurements were made during 1) spontaneous LES pressure fluctuations, 2) LES pressure changes induced by pharmacological agents, and 3) LES relaxation induced by vagal nerve stimulation. These studies show that 1) spontaneous LES pressure fluctuations correlated with spontaneous changes in LES longitudinal muscle contraction; 2) pharmacologically induced contraction and relaxation of LES pressure correlated with contraction and relaxation of LES longitudinal muscle, respectively; 3) a close temporal relationship existed between changes in LES longitudinal muscle contraction and LES pressure that occurred spontaneously or were induced pharmacologically; and 4) vagal stimulation caused LES longitudinal muscle contraction and LES pressure relaxation. We propose that LES longitudinal muscle may play a role in the modulation of intraluminal LES pressure.

Mechanisms of increased lower esophageal sphincter pressure following intraduodenal peptone infusion in dogs

Peptone perfusion of the excluded duodenum in dogs is associated with an increase in lower esophageal sphincter pressure (LESP). This study investigates the role of cholinergic, adrenergic, and hormonal mediators in the response of the LES to intraduodenal peptone infusion. Adult dogs underwent duodenal exclusion via a Roux-en-Y pylorojejunostomy with formation of a mucocutaneous fistula. Manometric measurements of LESP and radioimmunoassay determinations of gastrin and pancreatic polypeptide (PP) blood levels were made at rest and at 15-min intervals following peptone infusion of the excluded duodenum. In control experiments, peptone infusion resulted in an increase in mean LESP at all time intervals ( P < 0.05). PP blood levels increased significantly, while gastrin levels remained unchanged. Both truncal vagotomy and pretreatment with atropine blocked the changes in LESP. PP release in response to peptone was accentuated in vagotomized dogs, while atropine suppressed the release of PP following peptone infusion. Treatment with 6-hydroxydopamine did not affect the increase in either LESP or PP blood levels observed in controls. Intravenous somatostatin suppressed the release of PP following intraduodenal peptone, but did not block the lower esophageal sphincter response. This data indicates that the increase in LESP seen following intraduodenal peptone infusion is centrally mediated and dependent on vagal innervation and cholinergic neurotransmission.

Intravenous fat emulsion (intralipid•) delays gastric EMP-tying but does not affect lower esophageal sphincter pressure (LESP) in healthy volunteers

INTRAVENOUS FAT EMULSION (INTRALIPIDO) DELAYS GASTRIC EMPTYING BUT DOES NOT AFFECT LOWER ESOPHAGEAL SPHINCTER PRESSURE (LESP) IN HEALTHY VOLUNTEERS. P. Casaubon, K.A. Dahlstram, J. Vargas, R. Hawkins, M. Mogard, M.E. Ament. Department of Pediatrics. Medicine, and Nuclear Medicine, University of California, Los Angeles. Patients receiving overnight total parenteral nutrition frequently corrplain of nausea and upper abdominal discomfort after infusion of intravenous fat emulsion. The effects of infused lipid emulsion on upper gastrointestinal motility and gastrointestinal hormones (GIH) are unclear. This was evaluated in 10 healthy male volunteers (aged 28+1.5 SEM years). Group 1: 5 volunteers were studied over a 50 hour period in the Clinical Research Center. Esophageal manometry (EM) was done on admission (day 1) followed by intra-esophageal pH monitoring for 48 hours. They were fed a standardized diet (30% fat, 55% CHO, 15% proteins and 2000t 100 calories). On day 2, standard radionucleide gastTic emptying study was performed. Blood samples were taken just before and one hour after the gastric emptying for RIA of GIH (antibodies-Gastrin 1611, CCK 5135, neurotensin L170). On the second night. Intralipido 20% (500~~) was infused overnight for 10 hours. The iollowing morning, a second gastric emptying study was done in the last hour of the lipid infusion, and GIH were reassayed. The esophageal pH probe was then discontinued and Et4 repeated. Group 11: 5 other volunteers followed the same protocol, omitting EM and 48 hours pH because Group 1 subjects showed no significant change in LESP and reflux episodes before and after lipid infusion. Al1 volunteers after eating showed a significant rise in post prandial values of gastrin and CCK, but there was no significant change after lipid infuSion. Neurotensin values remained below 6 pM in al1 the samples. Gastric emptying showed a marked delay after lipid infusion in 8/10 volunteers (without lipids: 3724 SEM%; with lipids: 5424% of activity remaining in the stomach at 90 minutes, p=O.O04). Intravenous lipid emulsions delay gastric emptying. The gastric inhibitory mechanism does not appear to be mediated by the hormonal action of CCK or neurotensin.

701 APNEA AND LOWER ESOPHAGEAL SPHINCTER PRESSURE IN PRETERM INFANTS

We studied the maturation of the lower esophageal sphincter (LES) function in 17 infants without apnea at 29-41 wk postconceptual age (PCA) using an indwelling manometry system with a response rate of 90 mm Hg/sec. LES pressure was measured as the mean of peak pressures obtained during replicate pull-through maneuvers with a 3-lumen catheter. Initial studies obtained in each infant revealed no change in LES pressure with advancing fetal age. Subsequent studies revealed no change during 3 postnatal wks in LES pressure from the first wk pressure of 55.5 ± 4 (x + SE) mm Hg. However, LES pressure decreased in the 4th postnaTal wk corresponding with 36 wk PCA. We studied 26 additional infants of similar PCA who had apnea that was treated beginning at 7.7 ± 1.1 d with theophylline (THEO). The mean LES pressure in these infants was 69.2 ± 9.4 mm Hg before therapy and 75 ± 5.6 mm Hg during therapy, both greater values than that of infants without apnea (p < 0.0002). LES pressure did not decrease in apneic infants on THEO, but remained elevated for 7 postnatal wks. Conclusions: (1) LES pressures are greater in preterm infants than in older infants; (2) beginning at 36 wks PCA, LES pressures decrease in normal infants; (3) preterm infants with apnea have greater LES pressures before and during THEO therapy than preterm babies without apnea, suggesting an associated pathophysiologic mechanism that is not interrupted by THEO.

Effects of hindbrain stimulation on lower esophageal sphincter pressure in the cat.

Lower esophageal sphincter (LES) pressure was measured in anesthetized cats during electrical stimulation of the dorsal motor nucleus of the vagus (DMV) and nucleus ambiguus (NA). Stimulation parameters were varied to determine maximal changes in LES pressure and upper gastrointestinal motor responses. LES pressure decreased significantly during DMV and NA stimulation. The LES preferentially was affected over other upper gastrointestinal locations. Bradycardia and increases in blood pressure occurred with stimulation of both nuclei. LES pressure changes could be demonstrated in the absence of other gastrointestinal responses by decreasing hindbrain stimulation parameters. Cervical vagotomy completely eliminated hindbrain stimulation-induced changes in LES pressure, upper gastrointestinal motor activity, and heart rate. Similar frequency-LES pressure response relationships were observed for DMV and NA stimulation, with maximum changes occurring at 25 Hz. Changes in LES pressure occurred at shorter stimulation pulses (0.05 vs. 0.5 ms) and at lower stimulating current strength (30 vs. 60 microA) during DMV as compared with NA stimulation. In addition, stimulation of areas adjacent to the DMV and NA also significantly altered LES pressure, indicating that a large portion of the cat hindbrain associated with the vagal motor nuclei is involved in LES pressure control.

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.

Electrically coupled intrinsic responses of feline lower esophageal sphincter.

Intraluminal pressures and serosal myoelectric activity were recorded simultaneously from the esophagus, lower esophageal sphincter (LES), and stomach of chloralose-anesthetized cats. The LES demonstrated intermittent spike activity basally without slow waves and was distinct from esophagus and fundus. LES spike activity was not correlated with basal sphincter pressure. Dose-dependent increases in both spikes and pressure occurred with bethanechol, phenylephrine, or pentagastrin. Increased spike activity preceded the onset of the pressure rise and peaked during the rise in pressure. Changes in LES pressure and spike activity following these agents were correlated closely (r = 0.92, P less than 0.01). Atropine and isoproterenol inhibited pressure and spike activity similarly. Intrinsic reflexes to endogenous stimuli gave parallel spike and pressure changes. Distal esophageal acidification produced an increase in LES pressure that was correlated with increased spike activity. LES spike activity and pressure were inhibited similarly by antral distension or gastric acidification. Dissection of the distal esophagus from the diaphragm or bilateral cervical vagotomy had no effect on either LES spike activity or pressure. These studies indicate that a) LES myoelectric activity consists of spike discharges that are not correlated to resting pressure, b) abrupt changes in sphincter pressure following either intrinsic reflexes or neurohormonal agents are closely associated with similar changes in spike activity, and c) spike activity and sphincter pressure are intrinsic to the LES.