Lower Esophageal Sphincter Response Research Articles

Relaxation of the lower esophageal sphincter in response to reduced volume distension during FLIP Panometry.

The esophageal response to stepwise distension during the functional lumen imaging probe (FLIP) Panometry study often parallels high-resolution manometry (HRM) motility diagnoses. This study aimed to describe the changes in FLIP metrics during FLIP emptying, that is, reduced volume distension. Adult patients who completed FLIP and HRM for esophageal motility evaluation were included. Esophagogastric junction (EGJ) opening parameters were assessed during stepwise FLIP filling to volumes of 60 mL ("filling 60 mL"), then 70 mL, and then back to 60 mL ("emptying 60 mL"). HRM studies were analyzed per Chicago classification version 4.0 (CCv4.0). Among 265 patients included, HRM/CCv4.0 diagnoses included achalasia in 80 patients (30%), normal motility in 70 (26%), and ineffective esophageal motility (IEM) in 43 (16%). EGJ-distensibility index (DI) and EGJ diameter were greater during emptying 60 mL than filling 60 mL in achalasia, normal motility, and IEM (p values <0.002). If applying the emptying 60 mL EGJ-DI (vs. filling 60 mL EGJ-DI), EGJ opening classification changed from reduced EGJ opening to borderline EGJ opening in 31% of achalasia patients and in 2% of patients with normal motility or IEM. EGJ opening classification was unchanged in 69% achalasia and 96% of normal motility/IEM. This study suggests that isotonic or auxotonic relaxation of the lower esophageal sphincter occurs with reduced volume distension in patients with achalasia and normal motility. The study also supports the importance of utilizing a standardized FLIP motility study protocol (i.e., controlled, stepwise filling to 50 mL, 60 mL, then 70 mL) to provide reliable and generalizable FLIP metrics to facilitate diagnosis of esophageal motility disorders.

Laparoscopic Heller Myotomy with Dor Fundoplication: An Operation that has Withstood the Test of Time.

Achalasia is a primary esophageal motility disorder characterized by aperistalsis and defective relaxation of the lower esophageal sphincter in response to swallowing. Patients' symptoms include dysphagia, regurgitation, weight loss, chest pain and aspiration. The disease is idiopathic, and the goal of treatment is to eliminate the resistance determined by the abnormal lower esophageal sphincter, therefore allowing passage of the ingested food from the esophagus into the stomach. Three effective treatment modalities are available today-pneumatic dilatation, peroral endoscopic myotomy, and laparoscopic Heller myotomy with a partial fundoplication. We described the technique to perform a laparoscopic Heller myotomy and a Dor fundoplication. Five steps to perform a laparoscopic Heller myotomy and a Dor fundoplication were described. The surgical approach is favored in many centers as it is very effective in relieving symptoms, while avoiding pathologic gastroesophageal reflux in most patients.

The Evolution of the Treatment of Esophageal Achalasia: From the Open to the Minimally Invasive Approach

Achalasia is a primary esophageal motility disorder characterized by lack of esophageal peristalsis and partial or absent relaxation of the lower esophageal sphincter in response to swallowing. This study aimed to provide an overview of the evolution of the surgical treatment for esophageal achalasia, from the open to the minimally invasive approach. Literature review. No curative treatment exists for this disorder. At the beginning of the 20th century, surgical esophagoplasties and cardioplasties were mostly done to treat achalasia. The description of the esophageal myotomy by Heller changed the treatment paradigm and rapidly became the treatment of choice. For many years the esophagomyotomy was done with either an open transthoracic or transabdominal approach. With the advancements of minimally invasive surgery, thoracoscopic and laparoscopic operations became available. The ability to add a fundoplication for the prevention of reflux made the laparoscopic Heller myotomy with partial fundoplication the operation of choice. Surgical management of esophageal achalasia has significantly evolved in the last century. Currently, minimally invasive Heller myotomy with partial fundoplication is the standard surgical treatment of achalasia.

Physiological and pathological roles of the accommodation response in lower esophageal sphincter relaxation during wet swallows

The preparatory accommodation response of lower esophageal sphincter (LES) before swallowing is one of the mechanisms involved in LES relaxation during wet swallows, however, the physiological and/or pathological roles of LES accommodation remain to be determined in humans. To address this problem, we conducted a prospective observational study of 38 patients with normal high-resolution manometry (HRM) and 23 patients with idiopathic esophagogastric junction outflow obstruction (EGJOO) to assess dry and wet swallows. The LES accommodation measurement was proposed for practical use in evaluating the LES accommodation response. Although swallow-induced LES relaxation was observed in both dry and wet swallows, LES accommodation (6.4, 3.1–11.1 mmHg) was only observed in wet swallows. The extent of LES accommodation was impaired in idiopathic EGJOO (0.6, − 0.6–6 mmHg), and the LES accommodation measurement of patients with idiopathic EGJOO (36.8, 29.5–44.3 mmHg) was significantly higher in comparison to those with normal HRM (23.8, 18–28.6 mmHg). Successful LES relaxation in wet swallowing can be achieved by LES accommodation in combination with swallow-induced LES relaxation. Impaired LES accommodation is characteristic of idiopathic EGJOO. In addition to the IRP value, the LES accommodation measurement may be useful for evaluating the LES relaxation function in clinical practice.

Surgical management of achalasia.

Esophageal achalasia is a primary esophageal motility disorder characterized by lack of peristalsis and by incomplete or absent relaxation of the lower esophageal sphincter in response to swallowing. The cause of the disease is unknown. The goal of treatment is to eliminate the functional outflow obstruction at the level of the gastroesophageal junction, therefore allowing emptying of the esophagus into the stomach. They include the laparoscopic Heller myotomy with partial fundoplication, pneumatic dilatation, and peroral endoscopic myotomy. Esophagectomy is considered as a last resort for patients who have failed prior therapeutic attempts. In this evidence and experience‐based review, we will illustrate the technique and results of the surgical treatment of esophageal achalasia and compare it to the other available treatment modalities.

Laparoscopic Heller Myotomy and Dor Fundoplication: How I Do It?

Achalasia is a primary esophageal motility disorder characterized by lack of esophageal peristalsis and partial or absent relaxation of the lower esophageal sphincter in response to swallowing. Available treatment modalities are not curative but rather intend to relieve patient' symptoms. A laparoscopic Heller myotomy with Dor fundoplication is associated with high clinical success rates and low incidence of postoperative reflux. A properly executed operation following critical surgical steps is key for the success of the operation.

A rare ca(u)se of dysphagia

Achalasia is a rare lower esophageal motility disorder, in which there is destruction of myenteric plexi leading to the loss of esophageal peristalsis and inadequate relaxation of the lower esophageal sphincter in response to swallowing. Although the etiology of achalasia cardia is unclear, it is likely to be caused by autoimmune etiology. It is characterized by dysphagia of solids and liquids, regurgitation, weight loss, chest pain, heartburn, and nocturnal cough. Achalasia can be diagnosed on the clinical history and confirmed by barium swallow, and esophageal manometry which is the gold standard technique for diagnosis. Even though achalasia cannot be cured permanently, pneumatic balloon dilatation and myotomy remain the definitive treatment of choice in spite of availabilities of pharmacological therapies. We report a case of 25-year-old male admitted with chronic dysphagia and weight loss, diagnosed to be having achalasia cardia and treated accordingly.

Manometric Subtypes of Ineffective Esophageal Motility.

Objectives:Ineffective esophageal motility (IEM) is characterized by well-defined manometric criteria. However, much variation exists within the diagnosis: Some patients exhibit exactly the required five weak swallows to make the diagnosis. Others show consistently ineffective swallows with total absence of any normal swallow. “We hypothesize” there are two different manometric subtypes of IEM; IEM Alternans (IEM-A) and IEM Persistens (IEM-P).Methods:A total of 231 IEM patients were identified by high-resolution manometry (HRM). IEM defined by distal contractile integral (DCI) <450 mm Hg/s/cm in ≥50% of test swallows. Abnormal reflux study was defined by excess total number of reflux episodes, abnormal esophageal acid exposure, or positive symptom association.Results:A total of 195 (84%) patients had IEM-A and 36 (16%) had IEM-P. A striking gender difference with 34% of IEM-A being males compared to 53% of IEM-P. (P=0.03). Mean age of IEM-P (59.6 years+/−13.1) was greater than IEM-A (55.5 years+/−13.6) (P=0.04). Mean lower esophageal sphincter (LES) resting pressure was significantly lower in IEM-P (20.8 mm Hg+/−1.4) than IEM-A (29 mm Hg+/−1.2) (P=0.002). There was no difference in LES-integrated relaxation pressure (IRP), bolus transit, or manometric presence of hiatal hernia between the two groups. Out of 146, 89 (61%) patients had abnormal reflux study. Esophageal acid exposure in upright position was significantly higher in IEM-P than IEM-A (3.5 vs. 1.7%, P=0.04). Poor gastric acid control on proton pump inhibitor (PPI) was more prevalent among IEM-P patients (58%) than IEM-A (27%) (P=0.007). In subgroup analysis of 41 IEM patients with dysphagia, DCI for liquid swallows was significantly lower in IEM-P (111+/−142 mm Hg/s/cm) compared to IEM-A (421+/−502 mm Hg/s/cm) (P=0.04), lower mean LES resting pressure in IEM-P (16.6+/−9 mm Hg) than IEM-A (31.7+/−18 mm Hg) (P=0.01).Conclusions:There are two distinct manometric IEM subtypes; IEM-P with an older male predominance, more advanced reflux disease, weaker LES, and worse response to PPI; likely a more advanced manifestation than IEM-A. However, the question if there are different etiologies underlying the two subtypes remains to be answered.

Laparoscopic management of achalasia cardia

Background: Primary idiopathic Achalasia is a quite rare disease. Achalasia Cardia is a motor disorder of the esophagus and lower esophageal sphincter. More specifically, it is a neuromuscular disorder characterized by degenerative changes of the myenteric plexus leading to a selective loss of inhibitory nerve endings. Irreversible disruption of peristaltic contractions and impaired relaxation of the lower esophageal sphincter in response to deglutition are the consequences of this damage. There is always a need to find out the best possible management options for this condition. Methods: We studied 22 cases of Achalasia Cardia in a span of 2 years from November 2012 to November 2014. To confirm the diagnosis we subjected the patients to barium swallow, upper GI endoscopy and CT scanning. Esophageal Manometry and 24hr PH monitoring were not done, because of non-availability of it in our institute. Operative technique used was Laparoscopic Heller’s Cardiomyotomy with Dor’s 180 degree Partial Anterior Fundoplication. Results: Following laparoscopic surgery there was significant improvement in preoperative symptoms like dysphagia (95.5%), regurgitation (95.5%), chest pain (90.90%) and epigastric pain (100%). After addition of anti-reflux procedure there was significant reduction in post-operative reflux without development of any dysphagia which has to be noted. Conclusions: Laparoscopic Heller’s Cardiomyotomy with Dor’s Procedure is feasible, safe and better than open procedures. Laparoscopic Heller’s Cardiomyotomy should be the management of choice in achalasia cardia in expert hands and proper setup.

Heterogeneity of Lower Esophageal Sphincter Function in Children With Achalasia

Achalasia is a rare esophageal motor disorder in children. The manometric hallmarks are esophageal body aperistalsis, lack of lower esophageal sphincter (LES) relaxation, and high LES pressure. However, LES relaxation and function may be heterogeneous, making the diagnosis difficult at times. The aim of the study was to describe LES function in children with achalasia. The present study is a retrospective review of manometric tracings of pediatric patients with achalasia and controls. LES response after each swallow was evaluated. LES parameters were defined as homogeneous (normal or abnormal) if the same response was observed in >75% of swallows. Otherwise, the LES parameters were considered heterogeneous. Twenty-nine patients with achalasia and 16 control patients were included. All of the controls had normal LES pressure and relaxation in all of the wet swallows. In the achalasia group, some LES relaxation was present in 74% of swallows and 25% of swallows had normal relaxation. Depending on the parameter, a heterogeneous LES (resting pressure, relaxation, residual pressure, and duration of relaxation) was observed in 27.6% to 34.5% of patients with achalasia versus 0% of the controls (P < 0.001). The rest of the patients with achalasia had homogeneous abnormal responses versus homogeneous normal responses in 100% of control patients (P < 0.001). The LES function in pediatric patients with achalasia is heterogeneous. The classic description of a nonrelaxing high-pressure LES in patients with achalasia is rarely found in children. Partial relaxations are common, and normal relaxations may be present.

Serendipitous Diagnosis of Achalasia Cardia on a Radionuclide Study

Achalasia cardia is a motility disorder, involving the distal esophagus, resulting in elevated lower esophageal sphincter pressure, increased intraesophageal pressure, incomplete relaxation of lower esophageal sphincter in response to deglutition and loss of esophageal peristalsis. It usually presents between third and fifth decades of life with the most common symptom of dysphagia. We present a case of middle-aged lady who complained of intermittent vomiting after meal and excessive postprandial sense of fullness in abdomen. It was suspected to be related to delayed gastric emptying. Therefore, a gastric emptying time study was requested. The solid bolus of radioactive meal was held up in the lower end of esophagus, thereby suggesting achalasia. Barium meal examination confirmed the diagnosis.

Laparoscopic extended cardiomyotomy in children: an effective procedure for the treatment of esophageal achalasia

Purpose Achalasia of the esophagus is characterized by aperistalsis and incomplete relaxation of the lower esophageal sphincter in response to swallowing. The objective of the present study is to present the experience of a modified Heller myotomy via a laparoscopic approach for the treatment of children who had this condition. Methods A retrospective review of medical records of all patients who underwent this procedure from 2000 to 2009 was performed. The procedure consisted of an extended esophagomyotomy beginning on the lower part of the lower esophageal sphincter and continuing 5 to 6 cm above on the lower third of the esophagus, and then extended 3 to 4 cm below to the stomach, associated with an anterior 180-degree hemi-fundoplication according to Dor's technique. Results Fifteen patients were included in the study. There were 8 female and 7 male patients. Mean operating time was 190 minutes with no intraoperative complications and 1 conversion to open surgery because of difficulty in dissecting an inflamed distal esophagus. In a mean follow-up period of 32.3 months, 2 patients had recurrence of mild dysphagia that disappeared spontaneously, and 1 required a single botulinum toxin injection with complete resolution of symptoms. Conclusion We conclude that the laparoscopic extended Heller myotomy with Dor fundoplication is a safe and effective method for the treatment for achalasia in the pediatric population even in advanced cases.

Mechanism of stretch-activated excitatory and inhibitory responses in the lower esophageal sphincter

We recently found that an orally directed stretch of the esophagus activates a neurally mediated relaxation of the lower esophageal sphincter (LES). Goals of our study were to characterize the neural mechanisms responsible for axial and transverse stretch-activated responses in the LES. LES pressure was monitored in anesthetized and artificially ventilated mice. Sutures were placed in the esophagus to exert graded stretch in the longitudinal and transverse directions. Effects of bilateral vagotomy and pharmacological agents on the stretch-activated LES responses were investigated. The relationship between vagally stimulated axial stretch and LES relaxation was also studied. Stretch in the longitudinal and transverse directions caused a dose-dependent LES relaxation and contraction, respectively, that were not affected by bilateral vagotomy and sympathectomy but were blocked by tetrodotoxin. In bilateral vagotomized animals, hexamethonium, atropine, pyridoxalphosphate-6-azophenyl-2',4' disulfonic acid (PPADS), and ondansetron did not block the stretch-activated LES relaxation and contraction. Axial stretch-activated LES relaxation was blocked by nitric oxide inhibitor and transverse stretch-activated LES contraction was blocked by a combination of atropine and substance P antagonist. Electrical stimulation of the vagus nerve induced LES relaxation and axial stretch on the LES, both of which were blocked by rocuronium. Axial and transverse stretch-activated LES relaxation and contraction were present in the W/W(v) mice that lack interstitial cells of Cajal (ICC). Stretch-activated LES relaxation and contraction are mediated through mechanosensitive neurons located in the myenteric plexus, which involves neither synaptic transmission nor ICC.

Manometric Placement of BRAVO Capsule and Its Impact on Day to Day Discrepancy in Measurement of Esophageal Acid Exposure

Purpose: The wireless pH monitoring system (Bravo Capsule) is better tolerated and allows longer period of recording (48 hours) in patients evaluated for gastroesophageal reflux disease. The problem is that significant day to day discrepancy in measurement of acid exposure occurs. This variation is thought to be due to the sedation used during the endoscopic placement of the capsule. An alternative is placing the capsule transnasally based on motility measurements of the Lower Esophageal Sphincter (LES). We decided to assess if such a policy affects day to day discrepancy and if so, did the variability depend on the status of the gastroesophageal barrier. Methods: Study population consisted of 310 patients who had Bravo capsule placed transnasally based on manometric measurements of the LES. Based on composite score patients were divided in 3 groups: both days abnormal, both days normal and those with score discrepancy between first and second day. LES characteristic were compared in these groups. In addition, in the group with discrepancy the response of LES to a test meal was studied by calculating a post/pre prandial acid exposure ratio. Results: Of the 310 patients evaluated 60 (19%) had a discrepancy in score between the two days, 127 had a normal score and 123 an abnormal score on both days. Of the 60 patients with discrepancy, 27 were abnormal the first day and 33 were abnormal the second day. Patients with abnormal esophageal acid exposure on both days tend to have more defective LES compared to those with abnormal score only in one day. (33.3%, 51.2%, P= 0.027). Sphincter characteristic comparison for all 3 groups is shown (Table). In the 28 patients with discrepancy a test meal was given. Ten patients (36%) had an abnormal post/pre prandial acid exposure ratio on the normal day.TableConclusion: Manometric placement of Bravo capsule results in less discrepant pH recording between first and second 24 hours compared to previously reported placement via endoscopy. Patients with abnormal pH on both days tend to have a greater prevalence of defective valve than those with abnormal score on one day. This variability between the 2 days may represent impairment of gastroesophageal barrier in patients with early reflux disease.

Neuromotor Markers of Esophageal Motility in Feeding Intolerant Infants With Gastroschisis

Feeding problems in neonates with gastroschisis are commonly attributed to foregut dysmotility. However, the dysmotility mechanisms are not well understood. Our aim was to differentiate the pharyngoesophageal motility characteristics in neonates with gastroschisis compared with the controls. Specifically, the characteristics of swallowing, upper esophageal sphincter (UES), esophageal body, and lower esophageal sphincter (LES) were evaluated during basal state and upon provocation. Surgically repaired and recovered study infants with persistent feeding difficulties (n = 8; 36 +/- 2 weeks gestational age) and controls (n = 8; 38 +/- 2 weeks gestational age) were evaluated at 40 +/- 2 weeks and 42 +/- 2.5 weeks postmenstrual age, respectively. The basal and adaptive pharyngoesophageal motility characteristics were evaluated using a specially designed esophageal motility catheter with UES and LES sleeves and pneumohydraulic micromanometric water perfusion system at the crib side. Analysis of variance, chi-square, and t tests were applied; data are shown as mean +/- standard deviation, and P < 0.05 was considered significant. Birth weight was less in gastroschisis (P < 0.03, vs controls) and length was less at motility study (P < 0.01, vs controls). The study group (vs controls) needed prolonged respiratory support (21 +/- 23 vs 1 +/- 2 days; P < 0.001) and prolonged gavage feeding (167 +/- 100 vs 9 +/- 16 days; P < 0.01). Compared with the controls, the gastroschisis group had lower frequency (P < 0.05) and poor propagation of spontaneous swallows (P < 0.001), UES relaxation time was shorter (P < 0.05), rate of relaxation was faster (P < 0.001), and esophageal peristaltic propagation velocity was slower (P < 0.05). Upon esophageal provocation with air and liquids, frequency occurrence of the esophageal reflexes was low (P < 0.05) with respect to primary peristalsis, secondary peristalsis, UES contractile reflex, and LES relaxation reflex. In gastroschisis feeding milestones and respiratory milestones were delayed, basal pharyngoesophageal peristaltic failure was common, adaptive peristaltic reflexes were less frequent and failed to occur, and frequency occurrences of UES and LES responses were impaired. These neuromotor markers may provide clues to define the esophageal motor function abnormalities in infants with an abnormality thought to be limited to the intestine.

The effect of hydrocephalus on lower esophageal sphincter smooth muscle reactivity: experimental study

Purpose The aim of this study was to assess the pharmacophysiological significance of the enteric nervous system for the mechanical responses of lower esophageal sphincter (LES) in infantile rats with kaolin-induced hydrocephalus. Material and methods Hydrocephalus was created in 7-day-old rats by injection of kaolin into the cisterna magna. After 10 days, rats were decapitated. Contractile (KCl, carbachol) and relaxant (isoprenaline, papaverine) responses were determined by using in vitro muscle technique in isolated LES smooth muscle strips. Results The receptor-mediated contractile and relaxant response to carbachol and isoprenaline in the LES smooth muscle was impaired in rats with hydrocephalus. There was no significant difference in the KCl and papaverine response in hydrocephalic and sham operated rats. Conclusion Our findings suggest that hydrocephalus may impair receptor-mediated contractile and relaxant activity of LES smooth muscle leading to gastroesophageal reflux.

Coordinated gastric and sphincter motility evoked by intravenous CCK-8 as monitored by ultrasonomicrometry in rats.

Gastric and sphincter motility evoked by intravenous injection of CCK-8 were investigated in urethane-anesthetized rats. Digital ultrasonomicrometry was used to monitor pyloric (PYL), antral (ANT), corpus (COR), and lower esophageal sphincter (LES) movements while simultaneously measuring intragastric pressure (IGP) and, in some experiments, subdiaphragmatic intraesophageal pressure (sIEP). Intracrystal distances (ICD) were measured continuously between pairs of piezoelectric crystals affixed to the serosa of PYL, ANT, COR (circular and longitudinal), and LES. Consecutive intravenous injections of CCK-8 (0.3, 1, and 3 microg/kg) at 30-min intervals caused dose-dependent simultaneous tonic contractions of PYL and ANT, LES opening, and drops in IGP with peak changes at 3 microg/kg of -17.9 +/- 2.1, -7.7 +/- 2.5, 6.5 +/- 1.4, and -29.2 +/- 3.8%, respectively, whereas intravenous saline had no effect. Rhythmic contractile activity was inhibited by CCK-8. COR responses were not significantly different from vehicle controls for most metrics, and the direction of response for circular COR varied between preparations, although not for repeated trials in a single preparation. During the LES response to CCK-8, sIEP rose in parallel with drops in IGP, indicating formation of a common cavity. Recovery of LES ICD after intravenous CCK occurred more rapidly than recovery of PYL ICD, suggesting the importance of preventing simultaneous patency of gastroesophageal and gastroduodenal passages. The CCK(A) receptor antagonist devazepide (500 microg/kg intravenous) inhibited motion responses evoked by intravenous CCK-8. These data revealed CCK-8-induced gastric and sphincter activity consistent with retropulsion of gastric content.

Effect of Straining on the Lower Esophageal Sphincter: Identification of the “Straining-Esophageal Reflex” and Its Role in Gastroesophageal Competence Mechanism

The lower esophagus is intra-abdominal and exposed to intra-abdominal pressure (IAP) variations that may lead to gastroesophageal reflux (GER). We investigated the hypothesis that the lower esophageal sphincter (LES) undergoes phasic contraction on IAP increase, with a resulting inhibition of the stress GER. The study comprised 17 subjects (age 42.3 ± 8.7 SD yr, 10 men, 7 women) who were scheduled for surgical repair of abdominal hernia. The patients had no swallowing problems. The electromyographic (EMG) activity of the LES and pressure within the LES were recorded at rest and during increased IAP (coughing, straining). The recording was repeated after LES anesthetization or saline infiltration. The LES EMG at rest showed regular slow waves (SWs), superimposed on or followed by random action potentials (APs). Coughing or straining induced increase of the SWs parameters and also of the APs; although the increase with straining was less than with coughing, the difference was insignificant. Coughing or straining increased the LES pressure significantly (p<.05, p<.05, respectively). Ten minutes after LES anesthetization, coughing or straining did not produce significant LES EMG or pressure changes, while saline infiltration of LES caused LES response similar to preinjection. Thus, coughing and straining effected an increase of the LES EMG activity and pressure, an action presumably mediated through a reflex that we call the “straining-esophageal reflex.” This reflex seems to be evoked during increased intra-abdominal pressure and to effect LES contraction, thus, sharing with other factors in prevention of gastroesophageal reflux.

Effects of Hypoxia on Respiratory Neural Output and Lower Esophageal Sphincter Pressure in Piglets

We have previously documented anatomic and functional relationships between ventilatory and autonomic neural output. Therefore, we hypothesized in this study that hypoxia-induced changes in respiratory neural output are associated with changes in autonomic regulation of lower esophageal sphincter (LES) pressure. Respiratory neural output, heart rate, and LES pressure were measured before and during a 3-min exposure to 8% oxygen (balance nitrogen) in 12 3- to 7-d-old piglets. Respiratory neural output was determined from diaphragmatic electromyogram and LES pressure from an esophageal catheter. Studies were repeated after atropine administration in eight animals. Hypoxic exposure resulted in significant increases in diaphragmatic amplitude, respiratory rate, and minute diaphragmatic activity as well as heart rate. The biphasic response of diaphragm amplitude peaked at 1 min, whereas the responses of respiratory frequency and heart rate were sustained. Hypoxia caused a 50% increase in LES pressure (p < 0.05), which was eliminated by i.v. atropine administration. Development of apnea during subsequent hyperoxic exposure was always followed by a decline in LES pressure. Hypoxia-induced increase in respiratory neural output and accompanying increase in heart rate are associated with enhanced constrictive output to the LES. Blockade by atropine implicates a peripheral cholinergic mechanism for this LES response. We speculate that whereas hypoxia in the presence of enhanced respiratory neural output seems to be protective against reflux, decreased respiratory drive and accompanying apnea may be associated with a decline in LES tone and predispose to gastroesophageal reflux.

Baclofen blocks LES relaxation and crural diaphragm inhibition by esophageal and gastric distension in cats.

Esophageal distension and transient lower esophageal sphincter (LES) relaxation (TLESR) are accompanied by simultaneous relaxation of the LES and inhibition of crural diaphragm. Recent studies indicate that baclofen decreases the frequency of TLESR; however, its effect on the crural diaphragm is not known. We evaluated the effects of baclofen on LES relaxation and crural diaphragm inhibition induced by gastric distension and esophageal distension in cats. Five adult cats underwent surgical implantation of wire electrodes into the crural and costal diaphragm for measurement of their EMG activity, respectively. One week after the surgery, animals were lightly sedated and recordings were performed using a manometry catheter equipped with a 2.5-cm balloon. The effects of baclofen (10 micromol/kg iv) on the graded esophageal distension and gastric distension-induced LES and crural diaphragm responses were studied. Distension of the esophagus and stomach induces relaxation of the LES and inhibition of the crural diaphragm, simultaneously. Baclofen blocks both the esophageal and the gastric distension-induced relaxation of the LES and inhibition of the crural diaphragm. The magnitude of response to baclofen was significantly larger for the crural diaphragm inhibition than for the LES relaxation. Baclofen, a GABA(B) receptor agonist, blocks the reflex inhibitory pathway to the LES and crural diaphragm. The reflex inhibitory pathway to the crural diaphragm is more sensitive to blockade by baclofen than the reflex LES inhibitory pathway.