Patrick Sanvanson

A Human Model of Restricted Upper Esophageal Sphincter Opening and Its Pharyngeal and UES Deglutitive Pressure Phenomena

Oropharyngeal dysphagia due to upper esophageal sphincter (UES) dysfunction is commonly encountered in the clinical setting. Selective experimental perturbation of various components of the deglutitive apparatus can provide an opportunity to improve our understanding of the swallowing physiology and pathophysiology. The aim is to characterize the pharyngeal and UES deglutitive pressure phenomena in an experimentally induced restriction of UES opening in humans. We studied 14 volunteers without any dysphagic symptoms (7 men, 66 ± 11 yr) but with various supraesophageal reflux symptoms. To induce UES restriction, we used a handmade device that with adjustment could selectively apply 0, 20, 30, or 40 mmHg pressure perpendicularly to the cricoid cartilage. Deglutitive pharyngeal and UES pressure phenomena were determined during dry and 5- and 10-ml water swallows × 3 for each of the UES perturbations. External cricoid pressure against the UES resulted in a significant increase in hypopharyngeal intrabolus pressure and UES nadir deglutitive relaxation pressure for all tested swallowed volumes (P < 0.05). Application of external cricoid pressure increased the length of the UES high pressure zone from 2.5 ± 0.2 to 3.1 ± 0.2, 3.5 ± 0.1, and 3.7 ± 0.1 cm for 20, 30, and 40 mmHg cricoid pressure, respectively (P < 0.05). External cricoid pressure had no significant effect on pharyngeal peristalsis. On the other hand, irrespective of external cricoid pressure deglutitive velopharyngeal contractile integral progressively increased with increased swallowed volumes (P < 0.05). In conclusion, acute experimental restriction of UES opening by external cricoid pressure manifests the pressure characteristics of increased resistance to UES transsphincteric flow observed clinically without affecting the pharyngeal peristaltic contractile function.

Characterization of pharyngeal peristaltic pressure variability during volitional swallowing in healthy individuals

Recent technological advances incorporated in high resolution manometry have justifiably heightened interest in manometric evaluation of the pharynx. Despite this interest, from both physiologic and clinical perspective there remain a number of unanswered questions regarding the magnitude of variability of pharyngeal pressure phenomena. Therefore, the aim of the present study was to characterize in healthy individuals the inter‐subject and recording‐site specific variability of pharyngeal peristaltic pressure phenomena.

Pharyngeal Peristaltic Pressure Variability, Operational Range and functional Reserve

The present understanding of pharyngeal motor function remains incomplete. Among the remaining gaps of knowledge in this regard is the magnitude of variability of pharyngeal peristaltic pressure amplitude. Although variability can pose difficulty in interpretation of manometric findings, its magnitude can inform the operational range and reserve of the pharyngeal contractile function. We aimed to define the intra- and intersubject and intersession variability of select pharyngeal manometric parameters and, using this information, determine the number of swallow repetitions for acquiring reliable pharyngeal manometric data. We recorded pharyngeal peristalsis in 10 healthy subjects (age: 50 ± 25 yr, 5 women) by high-resolution manometry during two separate sessions of 20 sequences of 0.5-ml water swallows. Two-way ANOVA showed significant variation in the mean peak peristaltic pressure value across sites (P < 0.0001) as well as within the data at each site (P < 0.0001). Similarly, the pharyngeal contractile integral exhibited significant inter- (P = 0.003) and intrasubject (P < 0.001) variability. The Shapiro-Wilk normality test showed mixed results, in that some sites showed normally distributed data, whereas others did not. A robust Monte Carlo simulation showed that the nominal sample size was different for various tested metrics. For a power of 0.8, commonly accepted as an adequate threshold for acceptable statistical power, the optimal sample size for various peristaltic parameters ranged between 3 and 15. There is significant intra- and intersubject variability in site-specific and integrated parameters of pharyngeal peristalsis. The observed variance indicates a significant operational range and reserve in pharyngeal contractile function while necessitating parameter-specific sample size for reliable results.NEW & NOTEWORTHY Intra- and intersubject variability are significant and different at various sites within the contractile pharynx. In addition, significant swallow-to-swallow and subject-to-subject variability exists in pharyngeal contractile integral. The range of intrasubject variability indicates the existence of broad operational range and reserve. Lastly, our variability studies informed Monte Carlo and power analyses, yielding estimates of sample size that would ensure accurate representation of pressure metric variability.

UES Restrictive Disorders

The upper esophageal sphincter (UES) is a complex muscle structure that is composed of the cricopharyngeus muscle, the inferior pharyngeal constrictor muscle, and the proximal cervical esophagus. The UES plays an important role in the swallowing process and marks the transition from the pharyngeal deglutitive phase to the esophageal phase. Adequate UES opening is therefore essential for an effective swallow. Failed or diminished UES opening results in incomplete pharyngeal clearance, post-deglutitive residual, and potential post-deglutitive aspiration. Disordered UES opening can be the result of abnormal UES distensibility, such as Zenker’s diverticulum, cricopharyngeal bar, or lack of neural relaxation, such as cricopharyngeal achalasia. Alternatively, it can be due to weak pharyngeal propulsion alone or in addition to failed UES relaxation. For this review, we focus on intrinsic UES restrictive disorders. Major diagnostic tools include videofluoroscopy, endoscopic evaluation of the pharynx and esophagus, and pharyngoesophageal manometry. Treatment options for UES restrictive disorders depend on the underlying etiology and may include surgical or endoscopic methods.

Swallow strength training exercise for elderly: A health maintenance need

Recent studies have shown high prevalence of oropharyngeal dysphagia associated with frailty‐ and age‐related muscle weakness. Strength training exercises have been advocated for locomotive health maintenance in the elderly and have shown positive outcomes. As muscles involved in oropharyngeal phase of swallowing are also comprised of striated muscles, the aim of this study was to determine biomechanical effect of a novel resistance exercise program, Swallowing Against Laryngeal Restriction (SALR), on pharyngeal phase swallowing in the healthy elderly.

Upper esophageal sphincter augmentation reduces pharyngeal reflux in nasogastric tube-fed patients: Reducing Trans-UES Reflux in NGT-Fed Patients

Aspiration of gastric refluxate is one of the most commonly observed complications among long‐term nasogastric tube (NGT) fed patients. The upper esophageal sphincter (UES) pressure barrier is the main defense mechanism against pharyngeal reflux of gastric contents. Our objective was to investigate the efficacy and safety of the UES assist device (UES‐AD) in preventing gastric reflux through the UES in long‐term NGT‐fed patients.

Comparative effect of the sites of anterior cervical pressure on the geometry of the upper esophageal sphincter high-pressure zone

External cricoid pressure is increasingly used to augment the upper esophageal sphincter (UES). Our objective was to determine the effect of 1) pressures applied to cricoid, supracricoid, and subcricoid regions on the length and amplitude of the UES high‐pressure zone (UESHPZ), and 2) the external cricoid pressure on lower esophageal sphincter (LES) tone.

Sa2022 Subliminal Esophageal Acid Exposure Is Associated With an Increase of Right Insula Functional Connectivity in the Homeostatic Afferent Processing Network

Background/Aim: Excessive stress in modern society is associated with development of functional dyspepsia, which presents with symptoms of epigastric pain, early satiety and postprandial fullness. The central neural peptides, members of the corticotropin-releasing factor family, play key roles in response to stress. We previously reported that urocortin1 (UCN1) suppressed feeding behavior in fasted rats through an α2-adrenergic receptor (α2AR) activation, which decreases ghrelin secretion (DDW 2014). However, the influence of UCN1 on gastrointestinal (GI) function remains unclear. To elucidate this, we investigated the changes in gastric emptying and GI motility in UCN1-treated rats. Methods: UCN1 (300 pmol/rat) or phosphate-buffered saline (PBS) were intracerebroventricularly (ICV) injected to Sprague-Dawley rats, and gastric emptying and plasma ghrelin levels 2 h after oral administration of test meal were measured. The α2-AR antagonist, yohimbine (5 mg/kg) 15 min before ICV were intraperitoneal(IP) administered to UCN1-treated rats. Furthermore, ghrelin (3 nmol/rat, intravenous (IV)) were administered to UCN1-treated rats. In another set of experiment, the effects of co-administration of rikkunshito (RKT; 1000 mg/kg, which is an endogenous ghrelin enhancer) and with the ghrelin receptor antagonist ([D-Lys3] GHRP-6; 4 μmol/kg IV) was investigated. GI motility was investigated to determine the effects of ghrelin or RKT to UCN1-treated rats using a strain gauge force transducer in free-moving condition. Results: UCN1-treated rats exhibited significantly delayed gastric emptying. Administration of yohimbine improved gastric emptying (UCN1: 22.9±6.5 %, UCN1+yohimbine: 58.5±7.6 %, p<0.05) and significantly increased plasma ghrelin levels (UCN1:47.2±3.6 fmol/mL, UCN1+yohimbine: 81.9±7.8 fmol/mL, p<0.05). Exogenous administration of ghrelin restored delayed gastric empting. Administration of RKT significantly prevented delayed gastric empting and decreased plasma ghrelin levels. The gastric function of RKT was blocked by co-administration of the ghrelin receptor antagonist. ICV injection of UCN1 decreased the amplitude of contraction in the stomach while increasing the amplitude in the duodenum. Motility index of the stomach, but not the duodenum, was significantly reduced by treatment with UCN1 (PBS: 92.1 ± 10.1%, UCN1: 62.8 ± 4.7%), which was improved by the administration of ghrelin or RKT (99.03 ± 7.95%, p<0.05). Conclusions UCN1-induced gastric motility dysfunction with decrease in plasma ghrelin levels wasmediated byα2-AR activation. Disturbance in endogenous ghrelin dynamics play an important role in the functional abnormality of the upper GI tract under stressful conditions.

Tu2002 Effect of External Anterior Cervical Pressure Location on the UES High-Pressure Zone Is Site Specific

The mechanism by which air distension of the stomach leads to relaxation of the UES is unknown. AIM: To test the hypothesis that transient UES relaxation (TUESR) due to gastric air distension is secondary to activation of esophageal receptors caused by gastric gas escape. Methods: Decerebrate cats (N=10) were implanted with EMG electrodes on the cricopharyngeus (CP) to record UES tone, and a strain gauge on the lower esophageal sphincter (LES) to record LES tone. A gastric fistula was formed for the injection of air or a balloon into the stomach. The effects of the following procedures on gastric distension induced transient relation of the LES (TLESR) and TUESR were tested: gastric balloon distension, restriction of gastroesophageal (GEJ), or venting air from the distal esophagus. RESULTS: We found (N=5) that distension of the stomach with air (mean + SE= 65+ 10 ml) caused TLESR and TUESR. On the other hand, distension of the stomach with up to 150 ml of air in a non-distensible balloon (N=3) activate TLESR, but not TUESR. Restriction of the GEJ during air inflation (75 ml) of the stomach blocked TUESR, but not TLESR (N= 4). Venting the distal esophagus of air prevented air distension induced TUESR (N=3). CONCLUSIONS: TUESR is not related to gastric distension or any reflex associated with gastric distension, it is due gas escaping the stomach during the TLESR. This gas escape stimulates appropriate receptors in the esophagus causing the TUESR. Prior studies have found that air distension of the esophagus activates rapidly adapting mechanoreceptors of the esophageal mucosa activating eructation which includes TUESR.

336 A Human Model of Restricted UES Opening and Its Characteristic Pharyngeal and UES Deglutitive Pressure Phenomena

Introduction: Human disease models can help to better understand the pathophysiology and systematically characterize its consequences. Upper esophageal sphincter (UES) dysphagia is a common sequela of a number of disorders including CVA, reflux disease and aging. Intrinsic disorders of the UES such as fibrosis and inflammation can result in its diminished distensibility and restrict its opening causing dysphagia. Aim: To characterize the pharyngeal and UES deglutitive pressure phenomena in an experimentally induced restricted UES model in humans. Methods: We studied 15 patients (8 male, age 65±11 years) with various supraesophageal reflux symptoms. To induce UES restriction, we used a handmade simple device comprised of two components that could be comfortably worn around the neck: an elastic band and a cushion (5 X 3 X 2.5 CM). The cushion was placed horizontally at the center of the cricoid cartilage. By adjusting the elastic band, we selectively applied 0, 20, 30, 40 mmHg pressure perpendicular to the cricoid laryngeal structure inducing equivalent resistance against UES opening. In this model, the UES, in addition to relaxation, has to overcome the externally imparted pressure to open. Deglutitive pharyngeal and UES pressure phenomena were determined using high-resolution manometry, which recorded from entire pharynx, UES and proximal esophagus. We tested dry, 5 and 10ml swallows x 3. Results: Application of the external pressure band increased the length of the UES high pressure zone from 2.5 cm without the band to 3.1, 3.5 and 3.7 cm for 20, 30, 40mmHg cricoid restrictive pressure, respectively (p<0.05). Increased restrictive pressure against UES resulted in a significant increase in hypopharyngeal intra-bolus pressure (IBP) during all swallowed volumes (figure). Similarly, increased UES restrictive pressure resulted in increased UES nadir deglutitive relaxation pressure for all swallowed volumes (table, p<0.05). Swallowed volume had no effect on pharyngeal peak pressure, duration or velocity. None of these were affected by restrictive external UES pressures. Deglutitive velopharygeal pressure progressively increased with increased swallowed volume (p<0.05). These pressures were also not affected by UES restrictive external pressure. Conclusions: Acute experimental restriction of UES opening by external cricoid pressure in humans manifests the pressure characteristics of increased resistance to UES trans-sphincteric flow observed in disorders that are accompanied by reduced UES opening. These pressure characteristics include increased hypopharyngeal intra-bolus as well as nadir deglutitive UES relaxation pressures. This model can potentially be helpful in better understanding of UES pathophysiology. The effect of external cricoid (UES restrictive) pressure on UES nadir pressure