Esophageal Muscle Research Articles

PAX7 is required for patterning the esophageal musculature.

BackgroundThe mammalian esophageal musculature is unique in that it makes a transition from smooth to skeletal muscle, with most of this process occurring after birth. In order to better understand the mechanisms that control esophageal musculature development, we investigated the roles in this process of the paired box transcription factor, PAX7, a principal regulator of skeletal myogenic progenitor cells. Previous studies showed that Pax7 is important for determining the esophageal muscle composition.ResultsWe characterized the postnatal development of the esophageal musculature in Pax7−/− mice by analyzing morphology, muscle composition, and the expression of markers of myogenesis, cell proliferation, and apoptosis. Pax7−/− mice displayed megaesophagus with a severe defect in the postnatal developmental process whereby esophageal smooth muscle is replaced by skeletal muscle. Pax7−/− esophagi have substantially reduced skeletal muscle, most likely due to diminished proliferation and premature differentiation of skeletal muscle precursor cells. This impaired the proximal-to-distal progression of skeletal myogenesis and indirectly affected the patterning of the smooth muscle-containing portion of the esophageal musculature.ConclusionsPostnatal patterning of the esophageal musculature appears to require robust, PAX7-dependent cell proliferation to drive the proximal-to-distal progression of skeletal myogenesis. This process in turn influences distal smooth muscle morphogenesis and development of the mature pattern of the esophageal musculature.Electronic supplementary materialThe online version of this article (doi:10.1186/s13395-015-0068-0) contains supplementary material, which is available to authorized users.

Rigid substrate induces esophageal smooth muscle hypertrophy and eosinophilic esophagitis fibrotic gene expression

Cheng-Chiu Huang, PhD Yu Shin Kim, PhD William P. Olson, BS Fengxian Li, MD Changxiong Guo, BA Wenqin Luo, MD, PhD Andrew J. W. Huang, MD, MPH Qin Liu, PhD From the Department of Anesthesiology and the Center for the Study of Itch, Washington University School of Medicine, St Louis, Mo; the Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Md; the Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, Pa; the Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou, China; and the Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St Louis, Mo. E-mail: liuqi@anest. wustl.edu. This work was supported in part by the National Institutes of Health (grant no. R01EY024704 to Q. L.). Disclosure of conflict of interest: Q. Liu received research funding from the National Institutes of Health. The rest of the authors declare that they have no relevant conflicts of interest.

Does the capsaicin-sensitive local neural circuit constitutively regulate vagally evoked esophageal striated muscle contraction in rats?

To determine whether a capsaicin-sensitive local neural circuit constitutively modulates vagal neuromuscular transmission in the esophageal striated muscle or whether the neural circuit operates in a stimulus-dependent manner, we compared the motility of esophageal preparations isolated from intact rats with those in which capsaicin-sensitive neurons had been destroyed. Electrical stimulation of the vagus nerve trunk evoked contractile responses in the esophagus isolated from a capsaicin-treated rat in a manner similar to those in the esophagus from a control rat. No obvious differences were observed in the inhibitory effects of D-tubocurarine on intact and capsaicin-treated rat esophageal motility. Destruction of the capsaicin-sensitive neurons did not significantly affect latency, time to peak and duration of a vagally evoked twitch-like contraction. These findings indicate that the capsaicin-sensitive neural circuit does not operate constitutively but rather is activated in response to an applied stimulus.

Molecular characterization of systemic sclerosis esophageal pathology identifies inflammatory and proliferative signatures.

IntroductionEsophageal involvement in patients with systemic sclerosis (SSc) is common, but tissue-specific pathological mechanisms are poorly understood. There are no animal scleroderma esophagus models and esophageal smooth muscle cells dedifferentiate in culture prohibiting in vitro studies. Esophageal fibrosis is thought to disrupt smooth muscle function and lead to esophageal dilatation, but autopsy studies demonstrate esophageal smooth muscle atrophy and the absence of fibrosis in the majority of SSc cases. Herein, we perform a detailed characterization of SSc esophageal histopathology and molecular signatures at the level of gene expression.MethodsEsophageal biopsies were prospectively obtained during esophagogastroduodenoscopy in 16 consecutive SSc patients and 7 subjects without SSc. Upper and lower esophageal biopsies were evaluated for histopathology and gene expression.ResultsIndividual patient’s upper and lower esophageal biopsies showed nearly identical patterns of gene expression. Similar to skin, inflammatory and proliferative gene expression signatures were identified suggesting that molecular subsets are a universal feature of SSc end-target organ pathology. The inflammatory signature was present in biopsies without high numbers of infiltrating lymphocytes. Molecular classification of esophageal biopsies was independent of SSc skin subtype, serum autoantibodies and esophagitis.ConclusionsProliferative and inflammatory molecular gene expression subsets in tissues from patients with SSc may be a conserved, reproducible component of SSc pathogenesis. The inflammatory signature is observed in biopsies that lack large inflammatory infiltrates suggesting that immune activation is a major driver of SSc esophageal pathogenesis.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0695-1) contains supplementary material, which is available to authorized users.

Reduction of hydrogen sulfide synthesis enzymes in the esophagus of patients with achalasia: effect of hydrogen sulfide in achalasia.

The aim of the present study was to investigate whether the synthesis of endogenous hydrogen sulfide (H2 S) was altered in achalasia patients and to determine the effects of H2 S on esophageal motility. (1) Tissue samples in lower esophageal sphincter (LES) were obtained from 22 achalasia patients during peroral endoscopic myotomy. LES muscle from eight esophageal carcinoma patients was obtained as control. The expression of cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE) was detected by immunohistochemical staining. (2) Rabbit esophageal smooth muscle strips were used to measure isometric contractions. The effects of sodium hydrosulfide (NaHS) and L-cysteine on contractile activity and bethanechol-stimulated contractile activity were evaluated. The contraction of esophageal muscle strips was also measured after the inhibition of CBS and CSE by aminooxyacetic acid (AOA) and propargylglycine (PAG). Both CBS and CSE could be detected in biopsies from achalasia patients and controls. Compared with controls, the expression of CBS and CSE in the LES of achalasia patients was significantly reduced (p<0.001). Both NaHS and L-cysteine concentration-dependently inhibited esophageal contractile activity (both p<0.05). After inhibition of CBS and CSE by PAG and AOA, esophageal contractile activity increased significantly, and this effect could berestored by NaHS but not L-cysteine (p<0.05). H2 S synthesis enzymes are significantly reduced in patients with achalasia compared with the controls. H2 S inhibits esophageal contractile activity concentration-dependently, and the inhibition of H2 S synthesis enzymes increases esophageal contractile activity. H2 S might be involved in the development of achalasia.

A fully resolved active musculo-mechanical model for esophageal transport

Esophageal transport is a physiological process that mechanically transports an ingested food bolus from the pharynx to the stomach via the esophagus, a multi-layered muscular tube. This process involves interactions between the bolus, the esophagus, and the neurally coordinated activation of the esophageal muscles. In this work, we use an immersed boundary (IB) approach to simulate peristaltic transport in the esophagus. The bolus is treated as a viscous fluid that is actively transported by the muscular esophagus, and the esophagus is modeled as an actively contracting, fiber-reinforced tube. Before considering the full model of the esophagus, however, we first consider a standard benchmark problem of flow past a cylinder. Next a simplified version of our model is verified by comparison to an analytic solution to the tube dilation problem. Finally, three different complex models of the multi-layered esophagus, which differ in their activation patterns and the layouts of the mucosal layers, are extensively tested. To our knowledge, these simulations are the first of their kind to incorporate the bolus, the multi-layered esophagus tube, and muscle activation into an integrated model. Consistent with experimental observations, our simulations capture the pressure peak generated by the muscle activation pulse that travels along the bolus tail. These fully resolved simulations provide new insights into roles of the mucosal layers during bolus transport. In addition, the information on pressure and the kinematics of the esophageal wall resulting from the coordination of muscle activation is provided, which may help relate clinical data from manometry and ultrasound images to the underlying esophageal motor function.

Interspecies Differences in Electromechanical and Histological Characteristics of Human and Swine Esophagus1

Interspecies Differences in Electromechanical and Histological Characteristics of Human and Swine Esophagus1

Structure and motility of the esophagus from a mechanical perspective

Esophagus is an important part of the alimentary canal that performs various functions, most important of which is the transfer of bolus from the pharynx to the stomach. This involves active contraction of both the circular and longitudinal esophageal muscles. Esophageal anatomical features are harmonized with the functional and physiological demands of esophagus. However, impairment of esophageal functions may occur resulting in symptoms like dysphagia, gastroesophageal reflux or esophageal pain. This review covers broadly the anatomical and physiological details of esophagus, mechanical function of esophagus and its motility. In particular, the mechanical characteristics of the esophageal tissue and its motile function have been scrutinized. An overlay of the diagnostic technologies tapping these metrics is also covered.

The Signaling Mechanism of Contraction Induced by ATP and UTP in Feline Esophageal Smooth Muscle Cells.

P2 receptors are membrane-bound receptors for extracellular nucleotides such as ATP and UTP. P2 receptors have been classified as ligand-gated ion channels or P2X receptors and G protein-coupled P2Y receptors. Recently, purinergic signaling has begun to attract attention as a potential therapeutic target for a variety of diseases especially associated with gastroenterology. This study determined the ATP and UTP-induced receptor signaling mechanism in feline esophageal contraction. Contraction of dispersed feline esophageal smooth muscle cells was measured by scanning micrometry. Phosphorylation of MLC20 was determined by western blot analysis. ATP and UTP elicited maximum esophageal contraction at 30 s and 10 μM concentration. Contraction of dispersed cells treated with 10 μM ATP was inhibited by nifedipine. However, contraction induced by 0.1 μM ATP, 0.1 μM UTP and 10 μM UTP was decreased by U73122, chelerythrine, ML-9, PTX and GDPβS. Contraction induced by 0.1 μM ATP and UTP was inhibited by Gαi3 or Gαq antibodies and by PLCβ1 or PLCβ3 antibodies. Phosphorylated MLC20 was increased by ATP and UTP treatment. In conclusion, esophageal contraction induced by ATP and UTP was preferentially mediated by P2Y receptors coupled to Gαi3 and G q proteins, which activate PLCβ1 and PLCβ3. Subsequently, increased intracellular Ca2+ and activated PKC triggered stimulation of MLC kinase and inhibition of MLC phosphatase. Finally, increased pMLC20 generated esophageal contraction.

617. Histologic Assessment of Geriatric Esophagus Revels Therapeutic Targets in Wild-Type and Dystrophic Mouse Models

Gastroesophageal disorders increase as a process of aging and are exacerbated in degenerative neuromuscular disease such as Duchenne muscular dystrophy (DMD). DMD affects ≈1/5000 male births and is a catastrophic and ultimately fatal muscle wasting disease resulting from a mutation in the gene encoding the integral muscle protein dystrophin. Advancements in the treatment for DMD patients has increased patient lifespan and underscores a need to assess the impact of the disease in a range of organ systems, including the esophagus, likely to present new therapeutic challenges over time. Severity of esophageal pathology is varied to include reflux disease, achalasia, and megaesophagus. Defined as a pathologic enlargement of the esophagus, megaesophagus can result in a failure to complete peristalsis, impaction, severe weight loss and increased morbidity. Although poorly defined in human DMD patients, megaesophagus has been documented in canine and mouse models of DMD, however, a detailed cellular and mechanistic understanding remains unclear. We have performed a comprehensive morphologic and histologic examination of wild-type (C57/BL6) and dystrophic (mdx4cv) mouse esophagus to determine onset, pathology and changes in cellular composition accompanying megaesophagus onset. Age-associated presentation of megaesophagus was highly penetrant in both mouse models, with a four-fold increase in lumen dilation and coincident rate of impaction seen in aged dystrophic mice. In comparison, skeletal muscle area increased in both models with age, however, wild-type mice presented significantly greater hypertrophy than that observed in dystrophic mice. Interestingly, strain specific differences were not identified in esophagus mucosa strata with both strains presenting significant and similar increases in mucosa area and aging-dependent changes in mucosa composition. Further, a pronounced, aging-specific degradation of smooth musculature was observed in both mouse strains independent of dystrophin expression within wild-type mice. We demonstrate that esophageal smooth muscle is targetable via AAV-mediated gene therapy with future efforts aimed at correcting degeneration present within geriatric wild-type and dystrophic mouse models.

Histological study of the elongated esophagus in a rat model

BackgroundEsophageal elongation by traction suture is used in pediatric patients to manage long-gap esophageal atresia (EA). There was no histological evidence of the esophageal elongation. Here, we sought to clarify the histologic effects of traction on the esophagus by using a rat EA model simulating Foker's method. Materials and methodsRats were randomly assigned into three groups (n = 5 each). The traction group underwent daily stretching of the distal segment of the esophagus. The nontraction group underwent a sham operation, and the normal group served as controls. Seven days after the operation, the distal segments of the esophagus were removed. The length and thickness were measured, and samples were stained with Ki-67, nNOS, and S-100. ResultsThe whole length of the esophagus in the traction group was significantly longer than that in the nontraction group (P < 0.01). The thickness of esophageal mucosa and muscle tended to become thin by traction, but not significantly. The Ki-67-positive ratio of mucosa and muscle was significantly higher in the traction group (P < 0.05). There were no significant differences in Ki-67 between two segments (cardia-middle and middle-stump) in any group. Auerbach's plexus was identified at all sites of elongated esophagus by nNOS and S-100 staining. ConclusionsBy traction, the esophagus was elongated uniformly and cell proliferation activity was promoted in all parts of the elongated esophagus in the rat EA model.

The effects of acute tension increase on rat esophageal muscle contractions: An in vitro study

In long-gap esophageal atresia surgeries, anastomoses can be tensioned by several traction methods in order to establish esophageal continuity. It is unclear whether the etiology of esophageal dysmotility after traction is related with esophageal atresia itself or tensioned esophagus. Therefore, we evaluated the effects of acute in vitro esophageal tension application on esophageal muscle contractility in rats. 26 Wistar rats weighing 250–300g were included to the study. After diethyl ether anesthesia, proximal segment (PS) and distal segment (DS) of esophagus were removed and suspended in an isolated organ bath kept at 37°C, Krebs–Henseleit solution. Rats were enrolled into four groups including control group (CG, n=14) without tension, 5g (5G, n=4), 15g (15G, n=4) and 25g (25G, n=4) tension groups. In all groups, contractile responses to electrical field stimulation (EFS), carbachol and KCl, and relaxation responses to serotonin were obtained. In CG, higher contractile responses were obtained in PS than DS after EFS. Both PS and DS showed higher contractile amplitudes in 5G with respect to that of CG, 15G and 25G (p<0.05). In 5G, contractile responses to carbachol were significantly increased in both PS and DS with respect to CG (p<0.05). However, contractile amplitudes in response to carbachol were decreased in PS when tension was increased to 15g and 25g. In DS, contractile responses in 15G and 25G were lower than 5G, and still higher than CG. Serotonin relaxation responses in PS were decreased when compared to CG at tension levels of 5g, 15g and 25g (p<0.05). In DS, responses to serotonin were also decreased in tension groups. PS had higher contraction amplitudes than DS when contractile responses were obtained by high K+ (p<0.05). Tension groups of both PS and DS showed increased contractions to high K+ compared to CG (p<0.05). Increased esophageal tension led to increase in cholinergic responses of smooth muscles as well as in EFS-induced skeletal muscle responses. On the other hand, relaxation responses induced by serotonin decreased. These data indicate that esophageal tension increase impairs esophageal motility in both segments.

Optimizing Patient Selection and Outcomes for Surgical Treatment of GERD and Achalasia

Gastroesophageal reflux disease is a common disorder in the United States and other western countries. In addition to troublesome symptoms, this condition is associated with impaired quality of life and the potential for disease progression to esophageal adenocarcinoma. Acid suppression medications are extremely effective for the relief of heartburn symptoms, but don't address the physiologic derangements that cause reflux. The goal of an antireflux procedure is to correct these defects and abolish the dietary and lifestyle compromises that accompany medical therapy for gastroesophageal reflux. The Nissen fundoplication has a long and well-established track record and new options such as the LINX magnetic sphincter augmentation device allow correction of reflux with fewer side-effects than a fundoplication in appropriate patients. These options should be considered in patients incompletely satisfied on medical therapy and in those with risk factors for disease progression. The role of these therapies in patients with gastroesophageal reflux disease will be reviewed in this chapter. Achalasia is an uncommon motility disorder of the esophagus that leads to profound dysphagia symptoms and greatly impaired alimentary satisfaction. Pneumatic dilation offers an endoscopic approach to the management of these patients, but often requires repeated dilatations due to the inconsistent disruption of the lower esophageal sphincter with this technique. An alternative is a laparoscopic Heller myotomy, which offers precise division of the muscle of the lower esophageal sphincter, but requires incisions and lifestyle restrictions while healing. A new therapy, per-oral endoscopic myotomy, allows the precise division of the lower esophageal sphincter muscle as in a laparoscopic myotomy, but is done endoscopically with no external incisions. The role of these therapies in patients will be reviewed in this chapter.

Incidental Discovery of an Esophageal Leiomyoma: Thoracoscopic Surgical Approach

Background: Esophageal leiomyomas are the most common benign esophageal tumor, originating in the smooth muscle of the esophagus. Patients may accuse dysphagia, epigastric pain, but in 50% of cases are asymptomatic. Paraclinical exams used to highlight the esophageal tumor are esophageal and stomach barium swallow, esophagoscopy, chest CT scan, endoscopic ultrasonography. Thoracoscopic enucleation in recent years has gained many followers. Case Report: We present herein the case of 43 years old patient admitted in our department for thoracic trauma; the CT scan revealed a tumor in the middle third of the esophagus suggestive for a leiomyoma. Upper GI endoscopy showed an extrinsic compression in the middle third of the esophagus, without mucosal lesions, and esophageal barium swallow showed a slight narrowing of the lumen at this level. Given the findings suggestive of a benign esophageal tumor, possible esophageal leiomyoma, thoracoscopic approach was chosen. We performed a thoracoscopic enucleation with uneventful postoperative follow-up. Histopathology confirmed the diagnosis of esophageal leiomyoma. Conclusions: Thoracoscopic enucleation is a feasible method to treat esophageal leiomyomas.

Study on Sarcosystis Sp. By Light and Electron Microscopy in Camel Muscles at Assiut Governorate

Aims It is the 1st time to study sarcosysts meisheri of camels in Assiut Govemorate; throughout the study different parts from camels in different locations were examined for Sarcosystis meisheri. (Abdominal, esophagus and tongue muscles).Therefore, the present study aimed to investigate the prevalence of Sarcocystis meisheri . Infection among slaughtered camels in Assiut, Upper Egypt and to examine the ultrastructural characteristics of the sarcocystis meisheri inside the different muscles of camels. Main methods Random samples of different regions of camel muscles (0esophagus, tongue and abdominal region) were collected for examination of any Sarcocystis meisheri in muscles. Key findings One hundred and ninety five (195) specimens were examined. Only one hundred and eight (108) were found to be infected (55.5%).The infectious rates was highest in esophagus (62%), followed by abdominal muscles (52.2%) and tongue muscles (51.25%). Significance Generally the infectious rate with the parasite was higher in males than in females. Morphological and ultrastructures of muscle stage (sarcocyst) have been reported and illustrated in this study by both light and electron microscope. TEM showed that there are two types of Sarcocystis meisheri in camels in Assiut Governorate. The cyst consists of two types of cells these are metrocytes and merozoites and contained a large numbers of micronemes, rhopries, conoid and and mitochondrial organelles.

A Case of Deep Neck Abscess Extending to the Esophageal and Gastric Muscles

A Case of Deep Neck Abscess Extending to the Esophageal and Gastric Muscles

Achalasia--An Autoimmune Inflammatory Disease: A Cross-Sectional Study.

Idiopathic achalasia is a disease of unknown etiology. The loss of myenteric plexus associated with inflammatory infiltrates and autoantibodies support the hypothesis of an autoimmune mechanism. Thirty-two patients diagnosed by high-resolution manometry with achalasia were included. Twenty-six specimens from lower esophageal sphincter muscle were compared with 5 esophagectomy biopsies (control). Immunohistochemical (biopsies) and flow cytometry (peripheral blood) analyses were performed. Circulating anti-myenteric autoantibodies were evaluated by indirect immunofluorescence. Herpes simplex virus-1 (HSV-1) infection was determined by in situ hybridization, RT-PCR, and immunohistochemistry. Histopathological analysis showed capillaritis (51%), plexitis (23%), nerve hypertrophy (16%), venulitis (7%), and fibrosis (3%). Achalasia tissue exhibited an increase in the expression of proteins involved in extracellular matrix turnover, apoptosis, proinflammatory and profibrogenic cytokines, and Tregs and Bregs versus controls (P < 0.001). Circulating Th22/Th17/Th2/Th1 percentage showed a significant increase versus healthy donors (P < 0.01). Type III achalasia patients exhibited the highest inflammatory response versus types I and II. Prevalence of both anti-myenteric antibodies and HSV-1 infection in achalasia patients was 100% versus 0% in controls. Our results suggest that achalasia is a disease with an important local and systemic inflammatory autoimmune component, associated with the presence of specific anti-myenteric autoantibodies, as well as HSV-1 infection.

Ayurvedic management of achalasia.

Achalasia is an esophageal motor disorder characterized by sustained lower esophageal sphincter contraction and reduced esophageal peristalsis. This pathology eventually results in symptoms like dysphagia, regurgitation and occasional chest pain related to food intake. This is an uncommon disorder of unexplained etiology; however viral, autoimmune and neurodegenerative causes are often afflicted to its manifestation. As per the current state of knowledge, achalasia is considered to be a chronic incurable condition. The treatment options offered here primarily aim at reducing the tone of lower esophageal sphincter by pharmacologic, endoscopic or surgical means. We are presenting here a case of achalasia with two years of symptomatic history of food regurgitation, dysphagia and heart burn without any noticeable response from allopathic medicines. The patient was subsequently kept under ayurvedic therapy considering the symptoms caused by vata impairment and hence requiring vatanulomana and reduction in esophageal muscle tone as the primary management. The patient was kept under suggested Ayurvedic therapy and followed-up for 3 months. A symptom-free follow-up in this case was noticed after completion of 1 month of Ayurvedic therapy.

Murine and human tissue-engineered esophagus form from sufficient stem/progenitor cells and do not require microdesigned biomaterials.

Tissue-engineered esophagus (TEE) may serve as a therapeutic replacement for absent foregut. Most prior esophagus studies have favored microdesigned biomaterials and yielded epithelial growth alone. None have generated human TEE with mesenchymal components. We hypothesized that sufficient progenitor cells might only require basic support for successful generation of murine and human TEE. Esophageal organoid units (EOUs) were isolated from murine or human esophagi and implanted on a polyglycolic acid/poly-l-lactic acid collagen-coated scaffold in adult allogeneic or immune-deficient mice. Alternatively, EOU were cultured for 10 days in vitro prior to implantation. TEE recapitulated all key components of native esophagus with an epithelium and subjacent muscularis. Differentiated suprabasal and proliferative basal layers of esophageal epithelium, muscle, and nerve were identified. Lineage tracing demonstrated that multiple EOU could contribute to the epithelium and mesenchyme of a single TEE. Cultured murine EOU grew as an expanding sphere of proliferative basal cells on a neuromuscular network that demonstrated spontaneous peristalsis in culture. Subsequently, cultured EOU generated TEE. TEE forms after transplantation of mouse and human organ-specific stem/progenitor cells in vivo on a relatively simple biodegradable scaffold. This is a first step toward future human therapies.

Exaggerated smooth muscle contraction segments on esophageal high-resolution manometry: prevalence and clinical relevance.

Two smooth muscle contraction segments (S2, S3) on esophageal high-resolution manometry (HRM) demonstrate varying contraction vigor in symptomatic patients. Significance of isolated exaggerated smooth muscle contraction remains unclear. High-resolution manometry studies were reviewed in 272 consecutive patients (56.4± 0.8 years, 62% F) and compared to 21 healthy controls (27.6±0.6years, 52% F), using HRM tools (distal contractile integral, DCI; distal latency, DL; integrated relaxation pressure, IRP), Chicago Classification (CC) and multiple rapid swallows (MRS). Segments were designated merged when the trough between S2 and S3 was ≥150mmHg, and exaggerated S3 when peak S3 amplitude was ≥150mmHg without merging with S2. Presenting symptoms and global symptom severity (on 100mm visual analog scale) were recorded. Prevalence of merged and exaggerated segments was determined, and characteristics compared to symptomatic patients with normal HRM, and to healthy controls. Merged segments were identified in 5.6%, and exaggerated S3 in another 12.5%, but only 17-50% had a CC diagnosis; one healthy control had merged segments. DCI with wet swallows was similar in cohorts with merged and exaggerated segments (p=0.7), significantly higher than symptomatic patients with normal HRM and healthy controls (p≤0.003 for each comparison). Incomplete inhibition and prominent DCI augmentation on MRS (p≤0.01), and presenting symptoms (chest pain and dysphagia, p=0.04) characterized exaggerated segments, but not demographics or symptom burden. Merged esophageal smooth muscle segments and exaggerated S3 may represent hypermotility phenomena from abnormal inhibition and/or excitation, and are not uniformly identified by the CC algorithm.