A Unique Longitudinal Muscle Contraction Pattern Associated With Transient Lower Esophageal Sphincter Relaxation

Babaei, Arash; Bhargava, Valmik; Korsapati, Hariprasad Reddy; Zheng, Wei; Mittal, Ravinder K.

doi:10.1053/j.gastro.2008.02.031

Cited by 76 publications

(63 citation statements)

References 24 publications

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“…Esophageal pressures and high frequency intraluminal ultrasound (HFIUS) imaging of esophagus were performed simultaneously in the right lateral supine position with the head elevated to 30°. For 14 of the 18 subjects, we used data acquired from a previously published study in which pressures were recorded using a water perfused manometry system with a sleeve sensor that recorded LES pressure and 8 side holes that monitored pharyngeal, esophageal, and stomach pressure (4.5 cm catheter diameter) (1). Pressure data were acquired using an analog-to-digital converter, interfaced to a computer using Polygram 98 (Medtronic Synectics, Shoreview, MN) at a sampling rate of 16 Hz.…”

Section: Methodsmentioning

confidence: 99%

“…Studies show that during peristalsis CM and LM contract together cranial to the bolus (ascending contraction), to propel the bolus in the aboral direction, and they relax together around and caudal to the bolus (descending relaxation) (11), to receive the bolus. On the other hand, during TLESR, a unique LM contraction that starts in the distal esophagus and progresses in the cranial direction is observed (1,15). There is no significant contraction of the CM during TLESR.…”

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confidence: 90%

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Circular and longitudinal muscles shortening indicates sliding patterns during peristalsis and transient lower esophageal sphincter relaxation

Patel

Jiang

Mittal

et al. 2015

American Journal of Physiology-Gastrointestinal and Liver Physi

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Esophageal axial shortening is caused by longitudinal muscle (LM) contraction, but circular muscle (CM) may also contribute to axial shortening because of its spiral morphology. The goal of our study was to show patterns of contraction of CM and LM layers during peristalsis and transient lower esophageal sphincter (LES) relaxation (TLESR). In rats, esophageal and LES morphology was assessed by histology and immunohistochemistry, and function with the use of piezo-electric crystals and manometry. Electrical stimulation of the vagus nerve was used to induce esophageal contractions. In 18 healthy subjects, manometry and high frequency intraluminal ultrasound imaging during swallow-induced esophageal contractions and TLESR were evaluated. CM and LM thicknesses were measured (40 swallows and 30 TLESRs) as markers of axial shortening, before and at peak contraction, as well as during TLESRs. Animal studies revealed muscular connections between the LM and CM layers of the LES but not in the esophagus. During vagal stimulated esophageal contraction there was relative movement between the LM and CM. Human studies show that LM-to-CM (LM/CM) thickness ratio at baseline was 1. At the peak of swallow-induced contraction LM/CM ratio decreased significantly (Ͻ1), whereas the reverse was the case during TLESR (Ͼ2). The pattern of contraction of CM and LM suggests sliding of the two muscles. Furthermore, the sliding patterns are in the opposite direction during peristalsis and TLESR. muscularis propria; gastroesophageal reflux; unequal shortening of muscle layers THE ESOPHAGUS IS A RELATIVELY straight tube with simple functions, to transfer swallowed contents either from the mouth to the stomach or from the stomach toward the mouth as happens during vomiting, belching, and reflux. Prior studies have shown two distinct motor patterns in the esophagus: peristalsis that transports the swallowed contents aborally and transient lower esophageal sphincter (LES) relaxation (TLESR) that allows gastric contents to move into the esophagus toward the mouth. Inner circular muscle (CM) and outer longitudinal muscle (LM) layers play a key role in both oral and aboral movements of the bolus. Studies show that during peristalsis CM and LM contract together cranial to the bolus (ascending contraction), to propel the bolus in the aboral direction, and they relax together around and caudal to the bolus (descending relaxation) (11), to receive the bolus. On the other hand, during TLESR, a unique LM contraction that starts in the distal esophagus and progresses in the cranial direction is observed (1, 15). There is no significant contraction of the CM during TLESR.Axial stretch of esophagus in the oral direction activates neurologically mediated LES relaxation and possibly descending relaxation of the esophagus (7). Therefore, it is hypothesized that longitudinal muscle contraction related axial stretch is of fundamental importance in the descending relaxation of the peristaltic reflex. Axial esophageal shortening is generally thought to be caused b...

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 90%

Circular and longitudinal muscles shortening indicates sliding patterns during peristalsis and transient lower esophageal sphincter relaxation

Patel

Jiang

Mittal

et al. 2015

American Journal of Physiology-Gastrointestinal and Liver Physi

Self Cite

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“…W przeciwieństwie do relaksacji LES wyzwalanych połykaniem, TLESR trwają dłużej, nie zależą od połykania i towarzyszy im zahamowanie odnóg przepony. Ostatnie badania wskazują rów-nież, że TLESR wiążą się z odmiennym rodzajem skurczu podłużnej warstwy mięśniowej w dystalnej części przeły-ku [9]. Obecnie uważa się, że TLESR jest głównym mechanizmem leżącym u podłoża refluksu zarówno u osób zdrowych, jak i pacjentów z GERD.…”

Section: Samoistne Relaksacje Dolnego Zwiercza Przełykuunclassified

Reflux inhibitors – new therapy of gastroesophageal reflux disease

Jurkowska

Świdnicka-Siergiejko

Dâbrowski

2012

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S Sł ło ow wa a k kl lu uc cz zo ow we e: : refluks żołądkowo-przełykowy, spontaniczne relaksacje dolnego zwieracza przełyku, receptory GABA, receptory glutaminianu. K Ke ey y w wo or rd ds s: : gastroesophageal reflux, transient lower esophageal sphincter relaxation, GABA receptors, glutamate receptors. StreszczenieKontrola częstości występowania przemijających relaksacji dolnego zwieracza przełyku (transient lower esophgaeal relaxations -TLESR) jest najistotniejszym celem leczenia opornej choroby refluksowej przełyku. Występowanie TLESR stanowi główny mechanizm powstawania wszystkich typów refluksu. Aktualnie badane leki wpływające na redukcję występowania TLESR nazwano inhibitorami refluksu. Wśród nich najbardziej obiecujące wydają się agoniści receptora GABA B oraz antagoniści receptora 5 mGlu. Zmniejszają one liczbę refluksów i objawy związane z refluksem. Wydaje się, że oporna na leczenie choroba refluksowa przełyku jest potencjalnym wskazaniem do zastosowania inhibitorów refluksu jako terapii uzupełniającej w połączeniu z inhibitorem pompy protonowej. Przyszłe badania określą zapewne bezpieczeństwo i tolerancję tej nowej metody terapii antyrefluksowej. AbstractThe most relevant target for the treatment of refractory gastroesophageal reflux disease (GERD) is controlling the occurrence of transient lower esophageal relaxations (TLESR), which represent the main mechanism of all types of reflux. Drugs in development that have this mechanism of action are now described as reflux inhibitors. The most promising among these appear to be mGluR5 agonists and GABA B receptor agonists, which reduce the number of reflux episodes and improve reflux-related symptoms. Reflux inhibitors appear to have a potential role in the management of refractory GERD as add-on therapy in combination with PPI. Future studies will establish the safety and tolerability of the new anti-reflux therapy. WstępChoroba refluksowa przełyku (gastroesophageal reflux disease -GERD) dotyczy ponad 10% populacji krajów zachodnich. Celem leczenia GERD jest kontrola objawów, gojenie zmian zapalnych w przełyku i zapobieganie powikłaniom. Leczenie empiryczne z zastosowaniem leków hamujących wydzielanie kwasu solnego jest wła-ściwym postępowaniem u pacjentów z niepowikłaną zgagą. Inhibitory pompy protonowej (proton pomp inhibitors -PPI) są skuteczniejsze u tych chorych niż leki blokujące receptor H2, które z kolei są skuteczniejsze od placebo. Terapia GERD u wielu pacjentów nie stwarza problemów. Przypadki, w których podawanie PPI 2 razy dziennie nie zapewniło opanowania zgagi, powinno się uznać za niepowodzenie terapii i za racjonalną granicę leczenia emiprycznego [1]. Szacuje się, że 10-40% pacjentów z GERD nie odpowiada na standardową dawkę PPI częściowo lub całkowicie. Co więcej, w ciągu 7 lat (1997)(1998)(1999)(2000)(2001)(2002)(2003)(2004) zanotowano prawie 50-procentowy wzrost liczby chorych stosujących co najmniej podwójną dawkę PPI [2]. W jednym z ostatnich badań przeprowadzonych w Stanach Zjendoczonych w grupie 617 pacjentów z GERD 42,1% choryc...

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“…From this, the changes in the inner and outer margins of the muscularis are predicted by applying conservation of mass to the muscle layer, together with the assumption that material at each cross section moves only radially. Although we do not consider axial motions from potential shortening of longitudinal muscle of the esophagus (1,50), the results are relevant to this issue (see DISCUSSION).…”

Section: The Physio-mechanical Modelmentioning

confidence: 99%

“…All muscle mechanics studies done in the human esophagus, except for two notable exceptions (16,38), have assumed the esophageal wall to be "thin". 1 This incorrect assumption, although leading to great simplification of the mathematics, has important implications to the accuracy of predictions, so we do not make it. We use, instead, the full equations within finite deformation theory (34).…”

Section: The Physio-mechanical Modelmentioning

confidence: 99%

Liquid in the gastroesophageal segment promotes reflux, but compliance does not: a mathematical modeling study

Ghosh¹,

Kahrilas

Brasseur³

2008

American Journal of Physiology-Gastrointestinal and Liver Physi

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Ghosh SK, Kahrilas PJ, Brasseur JG. Liquid in the gastroesophageal segment promotes reflux, but compliance does not: a mathematical modeling study. Am J Physiol Gastrointest Liver Physiol 295: G920 -G933, 2008. First published August 21, 2008 doi:10.1152/ajpgi.90310.2008.-The mechanical force relationships that distinguish normal from chronic reflux at sphincter opening are poorly understood and difficult to measure in vivo. Our aim was to apply physics-based computer simulations to determine mechanical pathogenesis of gastroesophageal reflux. A mathematical model of the gastroesophageal segment (GES) was developed, incorporating the primary anatomical and physiomechanical elements that drive GES opening and reflux. In vivo data were used to quantify muscle stiffness, sphincter tone, and gastric pressure. The liquid lining the mucosa was modeled as an "effective liquid film" between the mucosa and a manometric catheter. Newton's second law was solved mathematically, and the space-time details of opening and reflux were predicted for systematic variations in gastric pressure increase, film thickness, muscle stiffness, and tone. "Reflux" was defined as "2 ml of refluxate entering the esophagus within 1 s." GES opening and reflux were different events. Both were sensitive to changes in gastric pressure and sphincter tone. Reflux initiation was extremely sensitive to the liquid film thickness; the protective function of the sphincter was destroyed with only 0.4 mm of liquid in the GES. Compliance had no effect on reflux initiation, but affected reflux volume. The presence of abnormal levels of liquid within the collapsed GES can greatly increase the probability for reflux, suggesting a mechanical mechanism that may differentiate normal reflux from gastroesophageal reflux disease. Compliance does not affect the probability for reflux, but affects reflux volume once it occurs. Opening without reflux suggests the existence of "gastroesophageal pooling" in the distal esophagus, with clinical implications. gastroesophageal reflux disease; lower esophageal sphincter; compliance; stiffness MUCH IS UNDERSTOOD ABOUT THE biomechanics underlying gastroesophageal reflux once refluxate flow into the esophagus has occurred, such as sphincter relaxation pressures (21), transsphincteric pressure gradient (46), hiatal distension (25), and the proximal extent of reflux (11). However, the mechanical differences that distinguish normal from chronic reflux are those that manifest at the time of opening and the initiation of reflux; these are less well understood. This lack of understanding of the initiation process is primarily because the initial opening process involves a level of mechanical subtlety in the balances among multiple forces and muscle deformations that are difficult to measure accurately in vivo due to rapid changes occurring over very short times with small changes in radial distention.The opening of the gastroesophageal segment (GES) and reflux result from dynamic adjustments in the subtle force balance that are initi...

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A Unique Longitudinal Muscle Contraction Pattern Associated With Transient Lower Esophageal Sphincter Relaxation

Cited by 76 publications

References 24 publications

Circular and longitudinal muscles shortening indicates sliding patterns during peristalsis and transient lower esophageal sphincter relaxation

Circular and longitudinal muscles shortening indicates sliding patterns during peristalsis and transient lower esophageal sphincter relaxation

Reflux inhibitors – new therapy of gastroesophageal reflux disease

Liquid in the gastroesophageal segment promotes reflux, but compliance does not: a mathematical modeling study

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