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Sphincter Mechanisms at the Esophago-Gastric Junction

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Abstract

Understanding of the sphincter mechanism at the esophago-gastric junction (EGJ) is crucial to the understanding of esophageal motor disorders and gastroesophageal reflux disease. Smooth muscles of the lower end of esophagus (LES) and skeletal muscles of crural diaphragm are the key components of sphincter mechanism at the EGJ. Basal LES tone/contraction is partly myogenic and party neurogenic. LES relaxation is mediated via the vagus nerve, which activates inhibitory motor neurons located in the esophageal wall. Longitudinal muscle contraction of the esophagus appears to play a critical role in the LES relaxation. LES and crural diaphragm relax together during transient LES relaxation (TLESR), which is the major mechanism of gastroesophageal reflux. TLESR is also important during belching, vomiting, and rumination. A large number of pharmacological agents decrease the TLESR frequency and could be potentially useful in the treatment of reflux disease. High-resolution and high-definition manometry has and will continue to improve our understanding of the complex functioning of EGJ.

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References

  1. Ingelfinger FJ. Esophageal motility. Physiol Rev. 1958;38:533–84.

    PubMed  CAS  Google Scholar 

  2. Code CF, Fyke Jr FE, Schlegel JF. The gastroesophageal sphincter in healthy human beings. Gastroenterologia. 1956;86:135–50.

    Article  PubMed  CAS  Google Scholar 

  3. Boyle JT, Altschuler SM, Nixon TE, Tuchman DN, Pack AI, Cohen S. Role of the diaphragm in the genesis of lower esophageal sphincter pressure in the cat. Gastroenterology. 1985;88:723–30.

    PubMed  CAS  Google Scholar 

  4. Liu J, Parashar VK, Mittal RK. Asymmetry of lower esophageal sphincter pressure: is it related to the ­muscle thickness or its shape? Am J Physiol. 1997;272:G1509–17.

    PubMed  CAS  Google Scholar 

  5. Liebermann-Meffert D, Allgower M, Schmid P, Blum AL. Muscular equivalent of the lower esophageal sphincter. Gastroenterology. 1979;76:31–8.

    PubMed  CAS  Google Scholar 

  6. Brasseur JG, Ulerich R, Dai Q, Patel DK, Soliman AM, Miller LS. Pharmacological dissection of the human gastro-oesophageal segment into three sphincteric components. J Physiol. 2007;580:961–75.

    Article  PubMed  CAS  Google Scholar 

  7. Seelig Jr LL, Goyal RK. Morphological evaluation of opossum lower esophageal sphincter. Gastroenterology. 1978;75:51–8.

    PubMed  Google Scholar 

  8. Delattre JF, Palot JP, Ducasse A, Flament JB, Hureau J. The crura of the diaphragm and diaphragmatic passage. Applications to gastroesophageal reflux, its investigation and treatment. Anat Clin. 1985;7:271–83.

    Article  PubMed  CAS  Google Scholar 

  9. Langman J. Medical Embryology. Philadelphia: William & Wilkins; 1975.

    Google Scholar 

  10. Mittal RK, Goyal RK. Sphincter mechanisms at the lower end of the esophagus. London: Nature Publishing; 2006.

    Google Scholar 

  11. Dodds WJ, Walter B. Cannon Lecture: current concepts of esophageal motor function: clinical implications for radiology. AJR Am J Roentgenol. 1977;128:549–61.

    PubMed  CAS  Google Scholar 

  12. Pandolfino JE, Zhang QG, Ghosh SK, Han A, Boniquit C, Kahrilas PJ. Transient lower esophageal sphincter relaxations and reflux: mechanistic analysis using concurrent fluoroscopy and high-resolution manometry. Gastroenterology. 2006;131:1725–33.

    Article  PubMed  Google Scholar 

  13. Beyak M, Bulmer D, Jiang W, Keating W, Grundy D. Extrinsic sensory affarent nerves innervating the gastrointestinal tract. New York: Academic; 2006.

    Google Scholar 

  14. Gershon MD. Genes and lineages in the formation of the enteric nervous system. Curr Opin Neurobiol. 1997;7:101–9.

    Article  PubMed  CAS  Google Scholar 

  15. Gershon MD. Developmental determinants of the independence and complexity of the enteric nervous system. Trends Neurosci. 2010;33:446–56.

    Article  PubMed  CAS  Google Scholar 

  16. Christensen J, Robison BA. Anatomy of the myenteric plexus of the opossum esophagus. Gastroenterology. 1982;83:1033–42.

    PubMed  CAS  Google Scholar 

  17. Christensen J, Rick GA, Robison BA, Stiles MJ, Wix MA. Arrangement of the myenteric plexus throughout the gastrointestinal tract of the opossum. Gastroenterology. 1983;85:890–9.

    PubMed  CAS  Google Scholar 

  18. Sengupta A, Paterson WG, Goyal RK. Atypical localization of myenteric neurons in the opossum lower esophageal sphincter. Am J Anat. 1987;180:342–8.

    Article  PubMed  CAS  Google Scholar 

  19. Brookes SJ, Hennig G, Schemann M. Identification of motor neurons to the circular muscle of the guinea pig gastric corpus. J Comp Neurol. 1998;397:268–80.

    Article  PubMed  CAS  Google Scholar 

  20. Yuan S, Costa M, Brookes SJ. Neuronal pathways and transmission to the lower esophageal sphincter of the guinea Pig. Gastroenterology. 1998;115:661–71.

    Article  PubMed  CAS  Google Scholar 

  21. Porter AJ, Wattchow DA, Brookes SJ, Costa M. The neurochemical coding and projections of circular muscle motor neurons in the human colon. Gastroenterology. 1997;113:1916–23.

    Article  PubMed  CAS  Google Scholar 

  22. Singaram C, Sengupta A, Stevens C, Spechler SJ, Goyal RK. Localization of calcitonin gene-related peptide in human esophageal Langerhans cells. Gastroenterology. 1991;100:560–3.

    PubMed  CAS  Google Scholar 

  23. Singaram C, Sengupta A, Sugarbaker DJ, Goyal RK. Peptidergic innervation of the human esophageal smooth muscle. Gastroenterology. 1991;101:1256–63.

    PubMed  CAS  Google Scholar 

  24. Singaram C, Sengupta A, Sweet MA, Sugarbaker DJ, Goyal RK. Nitrinergic and peptidergic innervation of the human oesophagus. Gut. 1994;35:1690–6.

    Article  PubMed  CAS  Google Scholar 

  25. Daniel EE, Posey-Daniel V. Neuromuscular structures in opossum esophagus: role of interstitial cells of Cajal. Am J Physiol. 1984;246:G305–15.

    PubMed  CAS  Google Scholar 

  26. Faussone-Pellegrini MS, Cortesini C. Ultrastructural features and localization of the interstitial cells of Cajal in the smooth muscle coat of human esophagus. J Submicrosc Cytol. 1985;17:187–97.

    PubMed  CAS  Google Scholar 

  27. Christensen J, Rick GA, Soll DJ. Intramural nerves and interstitial cells revealed by the Champy-Maillet stain in the opossum esophagus. J Auton Nerv Syst. 1987;19:137–51.

    Article  PubMed  CAS  Google Scholar 

  28. Sanders KM, Ward SM. Kit mutants and gastrointestinal physiology. J Physiol. 2007;578:33–42.

    Article  PubMed  CAS  Google Scholar 

  29. Ward SM, Sanders KM. Involvement of intramuscular interstitial cells of Cajal in neuroeffector transmission in the gastrointestinal tract. J Physiol. 2006;576:675–82.

    Article  PubMed  CAS  Google Scholar 

  30. Sanders KM, Ward SM. Interstitial cells of Cajal: a new perspective on smooth muscle function. J Physiol. 2006;576:721–6.

    Article  PubMed  CAS  Google Scholar 

  31. Huizinga JD, Zarate N, Farrugia G. Physiology, injury, and recovery of interstitial cells of Cajal: basic and clinical science. Gastroenterology. 2009;137:1548–56.

    Article  PubMed  Google Scholar 

  32. Ward SM, Morris G, Reese L, Wang XY, Sanders KM. Interstitial cells of Cajal mediate enteric inhibitory neurotransmission in the lower esophageal and pyloric sphincters. Gastroenterology. 1998;115:314–29.

    Article  PubMed  CAS  Google Scholar 

  33. Burns AJ, Lomax AE, Torihashi S, Sanders KM, Ward SM. Interstitial cells of Cajal mediate inhibitory neurotransmission in the stomach. Proc Natl Acad Sci U S A. 1996;93:12008–13.

    Article  PubMed  CAS  Google Scholar 

  34. Sivarao DV, Mashimo HL, Thatte HS, Goyal RK. Lower esophageal sphincter is achalasic in nNOS(-/-) and hypotensive in W/W(v) mutant mice. Gastroenterology. 2001;121:34–42.

    Article  PubMed  CAS  Google Scholar 

  35. Farre R, Wang XY, Vidal E, Domenech A, Pumarola M, Clave P, Huizinga JD, Jimenez M. Interstitial cells of Cajal and neuromuscular transmission in the rat lower oesophageal sphincter. Neurogastroenterol Motil. 2007;19:484–96.

    Article  PubMed  CAS  Google Scholar 

  36. Jiang Y, Bhargava V, Mittal RK. Mechanism of stretch-activated excitatory and inhibitory responses in the lower esophageal sphincter. Am J Physiol Gastrointest Liver Physiol. 2009;297:G397–405.

    Article  PubMed  CAS  Google Scholar 

  37. Zhang Y, Carmichael SA, Wang XY, Huizinga JD, Paterson WG. Neurotransmission in lower esophageal sphincter of W/Wv mutant mice. Am J Physiol Gastrointest Liver Physiol. 2010;298:G14–24.

    Article  PubMed  CAS  Google Scholar 

  38. Clouse RE, Staiano A. Topography of the esophageal peristaltic pressure wave. Am J Physiol. 1991;261:G677–84.

    PubMed  CAS  Google Scholar 

  39. Clouse RE, Staiano A. Topography of normal and high-amplitude esophageal peristalsis. Am J Physiol. 1993;265:G1098–107.

    PubMed  CAS  Google Scholar 

  40. Rohof WO, Boeckxstaens GE, Hirsch DP. High-resolution esophageal pressure topography is superior to conventional sleeve manometry for the detection of transient lower esophageal sphincter relaxations associated with a reflux event. Neurogastroenterol Motil. 2011;23(5):427–32.

    Article  PubMed  CAS  Google Scholar 

  41. Jones MP, Sloan SS, Rabine JC, Ebert CC, Huang CF, Kahrilas PJ. Hiatal hernia size is the dominant determinant of esophagitis presence and severity in gastroesophageal reflux disease. Am J Gastroenterol. 2001;96:1711–7.

    Article  PubMed  CAS  Google Scholar 

  42. Hong SJ, Bhargava V, Jiang Y, Denboer D, Mittal RK. A unique esophageal motor pattern that involves longitudinal muscles is responsible for emptying in achalasia esophagus. Gastroenterology. 2010; 139:102–11.

    Article  PubMed  Google Scholar 

  43. Kahrilas PJ, Ghosh SK, Pandolfino JE. Challenging the limits of esophageal manometry. Gastroenterology. 2008;134:16–8.

    Article  PubMed  Google Scholar 

  44. Miller LS, Liu JB, Colizzo FP, Ter H, Marzano J, Barbarevech C, Helwig K, Leung L, Goldberg BB, Hedwig K. Correlation of high-frequency esophageal ultrasonography and manometry in the study of esophageal motility. Gastroenterology. 1995;109:832–7.

    Article  PubMed  CAS  Google Scholar 

  45. Mittal RK, Liu J, Puckett JL, Bhalla V, Bhargava V, Tipnis N, Kassab G. Sensory and motor function of the esophagus: lessons from ultrasound imaging. Gastroenterology. 2005;128:487–97.

    Article  PubMed  Google Scholar 

  46. Boesmans W, Vanden Berghe P, Farre R, Sifrim D. Oesophageal shortening: in vivo validation of high-frequency ultrasound measurements of oesophageal muscle wall thickness. Gut. 2010;59:433–40.

    Article  PubMed  Google Scholar 

  47. Nicosia MA, Brasseur JG, Liu JB, Miller LS. Local longitudinal muscle shortening of the human esophagus from high-frequency ultrasonography. Am J Physiol Gastrointest Liver Physiol. 2001;281:G1022–33.

    PubMed  CAS  Google Scholar 

  48. Heine KJ, Mittal RK. Lower esophageal sphincter: how to quantitate? Gastroenterology. 1992;103:346–7.

    PubMed  CAS  Google Scholar 

  49. Ott DJ, Gelfand DW, Wu WC, Castell DO. Esophagogastric region and its rings. AJR Am J Roentgenol. 1984;142:281–7.

    PubMed  CAS  Google Scholar 

  50. Mittal RK, Balaban DH. The esophagogastric junction. N Engl J Med. 1997;336:924–32.

    Article  PubMed  CAS  Google Scholar 

  51. Mittal RK. The crural diaphragm, an external lower esophageal sphincter: a definitive study. Gastroenterology. 1993;105:1565–7.

    Article  PubMed  CAS  Google Scholar 

  52. Kahrilas PJ, Lin S, Chen J, Manka M. The effect of hiatus hernia on gastro-oesophageal junction pressure. Gut. 1999;44:476–82.

    Article  PubMed  CAS  Google Scholar 

  53. Preiksaitis HG, Diamant NE. Regional differences in cholinergic activity of muscle fibers from the human gastroesophageal junction. Am J Physiol. 1997;272:G1321–7.

    PubMed  CAS  Google Scholar 

  54. Goyal RK, Rattan S. Neurohumoral, hormonal, and drug receptors for the lower esophageal sphincter. Gastroenterology. 1978;74:598–619.

    PubMed  CAS  Google Scholar 

  55. Christensen J. Oxygen dependence of contractions in esophageal and gastric pyloric and ileocecal muscle of opossums. Proc Soc Exp Biol Med. 1982;170:194–202.

    PubMed  CAS  Google Scholar 

  56. Biancani P, Goyal RK, Phillips A, Spiro HM. Mechanics of sphincter action. Studies on the lower esophageal sphincter. J Clin Invest. 1973;52:2973–8.

    Article  PubMed  CAS  Google Scholar 

  57. Yamato S, Saha JK, Goyal RK. Role of nitric oxide in lower esophageal sphincter relaxation to swallowing. Life Sci. 1992;50:1263–72.

    Article  PubMed  CAS  Google Scholar 

  58. Goyal RK, Rattan S. Genesis of basal sphincter pressure: effect of tetrodotoxin on lower esophageal sphincter pressure in opossum in vivo. Gastroenterology. 1976;71:62–7.

    PubMed  CAS  Google Scholar 

  59. Szymanski PT, Szymanska G, Goyal RK. Differences in calmodulin and calmodulin-binding proteins in phasic and tonic smooth muscles. Am J Physiol Cell Physiol. 2002;282:C94–104.

    PubMed  CAS  Google Scholar 

  60. Biancani P, Hillemeier C, Bitar KN, Makhlouf GM. Contraction mediated by Ca2+ influx in esophageal muscle and by Ca2+ release in the LES. Am J Physiol. 1987;253:G760–6.

    PubMed  CAS  Google Scholar 

  61. Biancani P. Signal transduction in lower esophageal sphincter circular muscle. GI Motility online. 2006;doi: 10.1038/gimo24.

  62. Papasova M, Milousheva E, Bonev A, Boev K, Kortezova N. On the changes in the membrane potential and the contractile activity of the smooth muscle of the lower esophageal and ileo-caecal sphincters upon increased K in the nutrient solution. Acta Physiol Pharmacol Bulg. 1980;6:41–9.

    PubMed  CAS  Google Scholar 

  63. Saha JK, Sengupta JN, Goyal RK. Role of chloride ions in lower esophageal sphincter tone and relaxation. Am J Physiol. 1992;263:G115–26.

    PubMed  CAS  Google Scholar 

  64. Asoh R, Goyal RK. Electrical activity of the opossum lower esophageal sphincter in vivo. Its role in the basal sphincter pressure. Gastroenterology. 1978;74:835–40.

    PubMed  CAS  Google Scholar 

  65. Behar J, Kerstein M, Biancani P. Neural control of the lower esophageal sphincter in the cat: studies on the excitatory pathways to the lower esophageal sphincter. Gastroenterology. 1982;82:680–8.

    PubMed  CAS  Google Scholar 

  66. Martin CJ, Dodds WJ, Liem HH, Dantas RO, Layman RD, Dent J. Diaphragmatic contribution to gastroesophageal competence and reflux in dogs. Am J Physiol. 1992;263:G551–7.

    PubMed  CAS  Google Scholar 

  67. Dodds WJ, Dent J, Hogan WJ, Arndorfer RC. Effect of atropine on esophageal motor function in humans. Am J Physiol. 1981;240:G290–6.

    PubMed  CAS  Google Scholar 

  68. Mittal RK, Fisher M, McCallum RW, Rochester DF, Dent J, Sluss J. Human lower esophageal sphincter pressure response to increased intra-abdominal pressure. Am J Physiol. 1990;258:G624–30.

    PubMed  CAS  Google Scholar 

  69. Preiksaitis HG, Tremblay L, Diamant NE. Cholinergic responses in the cat lower esophageal sphincter show regional variation. Gastroenterology. 1994;106:381–8.

    PubMed  CAS  Google Scholar 

  70. Brookes SJ, Chen BN, Hodgson WM, Costa M. Characterization of excitatory and inhibitory motor neurons to the guinea pig lower esophageal sphincter. Gastroenterology. 1996;111:108–17.

    Article  PubMed  CAS  Google Scholar 

  71. Muinuddin A, Kang Y, Gaisano HY, Diamant NE. Regional differences in L-type Ca2+ channel expression in feline lower esophageal sphincter. Am J Physiol Gastrointest Liver Physiol. 2004;287:G772–81.

    Article  PubMed  CAS  Google Scholar 

  72. L’Heureux MC, Muinuddin A, Gaisano HY, Diamant NE. Feline lower esophageal sphincter sling and circular muscles have different functional inhibitory neuronal responses. Am J Physiol Gastrointest Liver Physiol. 2006;290:G23–9.

    Article  PubMed  CAS  Google Scholar 

  73. Goyal RK, Rattan S. Nature of the vagal inhibitory innervation to the lower esophageal sphincter. J Clin Invest. 1975;55:1119–26.

    Article  PubMed  CAS  Google Scholar 

  74. Chang HY, Mashimo H, Goyal RK. Musings on the wanderer: what’s new in our understanding of vago-vagal reflex? IV. Current concepts of vagal efferent projections to the gut. Am J Physiol Gastrointest Liver Physiol. 2003;284:G357–66.

    PubMed  CAS  Google Scholar 

  75. Rossiter CD, Norman WP, Jain M, Hornby PJ, Benjamin S, Gillis RA. Control of lower esophageal sphincter pressure by two sites in dorsal motor nucleus of the vagus. Am J Physiol. 1990;259:G899–906.

    PubMed  CAS  Google Scholar 

  76. Fournet J, Snape Jr WJ, Cohen S. Sympathetic control of lower esophageal sphincter function in the cat. Action of direct cervical and splanchnic nerve stimulation. J Clin Invest. 1979;63:562–70.

    Article  PubMed  CAS  Google Scholar 

  77. DiMarino AJ, Cohen S. The adrenergic control of lower esophageal sphincter function. An experimental model of denervation supersensitivity. J Clin Invest. 1973;52:2264–71.

    Article  PubMed  CAS  Google Scholar 

  78. Sarma DN, Banwait K, Basak A, DiMarino AJ, Rattan S. Inhibitory effect of beta3-adrenoceptor agonist in lower esophageal sphincter smooth muscle: in vitro studies. J Pharmacol Exp Ther. 2003;304:48–55.

    Article  PubMed  CAS  Google Scholar 

  79. Dimarino M, Banwait K, Rattan S, Cohen S, DiMarino AJ. Beta3 adrenergic stimulation inhibits the opossum lower esophageal sphincter. Gastroenterology. 2002;123:1508–15.

    Article  PubMed  CAS  Google Scholar 

  80. Dent J, Dodds WJ, Sekiguchi T, Hogan WJ, Arndorfer RC. Interdigestive phasic contractions of the human lower esophageal sphincter. Gastroenterology. 1983;84:453–60.

    PubMed  CAS  Google Scholar 

  81. Holloway RH, Blank E, Takahashi I, Dodds WJ, Layman RD. Motilin: a mechanism incorporating the opossum lower esophageal sphincter into the migrating motor complex. Gastroenterology. 1985;89:507–15.

    PubMed  CAS  Google Scholar 

  82. Holloway RH, Blank E, Takahashi I, Dodds WJ, Hogan WJ, Dent J. Variability of lower esophageal sphincter pressure in the fasted unanesthetized opossum. Am J Physiol. 1985;248:G398–406.

    PubMed  CAS  Google Scholar 

  83. Itoh Z, Aizawa I, Honda R, Hiwatashi K, Couch EF. Control of lower-esophageal-sphincter contractile activity by motilin in conscious dogs. Am J Dig Dis. 1978;23:341–5.

    Article  PubMed  CAS  Google Scholar 

  84. Holloway RH, Blank EL, Takahashi I, Dodds WJ, Dent J, Sarna SK. Electrical control activity of the lower esophageal sphincter in unanesthetized opossums. Am J Physiol. 1987;252:G511–21.

    PubMed  CAS  Google Scholar 

  85. Lind JF, Warrian WG, Wankling WJ. Responses of the gastroesophageal junctional zone to increases in abdominal pressure. Can J Surg. 1966;9:32–8.

    PubMed  CAS  Google Scholar 

  86. Ryan JP, Snape Jr WJ, Cohen S. Influence of vagal cooling on esophageal function. Am J Physiol. 1977;232:E159–64.

    PubMed  CAS  Google Scholar 

  87. Dogan I, Puckett JL, Padda BS, Mittal RK. Prevalence of increased esophageal muscle thickness in patients with esophageal symptoms. Am J Gastroenterol. 2007;102:137–45.

    Article  PubMed  Google Scholar 

  88. Reynolds RP, El-Sharkawy TY, Diamant NE. Lower esophageal sphincter function in the cat: role of central innervation assessed by transient vagal blockade. Am J Physiol. 1984;246:G666–74.

    PubMed  CAS  Google Scholar 

  89. Reynolds RP, Effer GW. The effect of differential vagal nerve cooling on feline esophageal function. Clin Invest Med. 1988;11:452–6.

    PubMed  CAS  Google Scholar 

  90. Rattan S, Goyal RK. Neural control of the lower esophageal sphincter: influence of the vagus nerves. J Clin Invest. 1974;54:899–906.

    Article  PubMed  CAS  Google Scholar 

  91. Gilbert R, Rattan S, Goyal RK. Pharmacologic identification, activation and antagonism of two muscarine receptor subtypes in the lower esophageal sphincter. J Pharmacol Exp Ther. 1984;230:284–91.

    PubMed  CAS  Google Scholar 

  92. Murray JA, Ledlow A, Launspach J, Evans D, Loveday M, Conklin JL. The effects of recombinant human hemoglobin on esophageal motor functions in humans. Gastroenterology. 1995;109:1241–8.

    Article  PubMed  CAS  Google Scholar 

  93. Knudsen MA, Svane D, Tottrup A. Action profiles of nitric oxide, S-nitroso-L-cysteine, SNP, and NANC responses in opossum lower esophageal sphincter. Am J Physiol. 1992;262:G840–6.

    PubMed  CAS  Google Scholar 

  94. Tottrup A, Svane D, Forman A. Nitric oxide mediating NANC inhibition in opossum lower esophageal sphincter. Am J Physiol. 1991;260:G385–9.

    PubMed  CAS  Google Scholar 

  95. Conklin JL, Du C, Murray JA, Bates JN. Characterization and mediation of inhibitory junction potentials from opossum lower esophageal sphincter. Gastroenterology. 1993;104:1439–44.

    PubMed  CAS  Google Scholar 

  96. Murray J, Bates JN, Conklin JL. Nerve-mediated nitric oxide production by opossum lower esophageal sphincter. Dig Dis Sci. 1994;39:1872–6.

    Article  PubMed  CAS  Google Scholar 

  97. Said SI, Rattan S. The multiple mediators of neurogenic smooth muscle relaxation. Trends Endocrinol Metab. 2004;15:189–91.

    Article  PubMed  CAS  Google Scholar 

  98. Murthy KS, Grider JR, Jin JG, Makhlouf GM. Interplay of VIP and nitric oxide in the regulation of neuromuscular function in the gut. Ann N Y Acad Sci. 1996;805:355–62. discussion 362–3.

    Article  PubMed  CAS  Google Scholar 

  99. Barnette M, Torphy TJ, Grous M, Fine C, Ormsbee 3rd HS, Cyclic GMP. a potential mediator of neurally- and drug-induced relaxation of opossum lower esophageal sphincter. J Pharmacol Exp Ther. 1989;249:524–8.

    PubMed  CAS  Google Scholar 

  100. Torphy TJ, Fine CF, Burman M, Barnette MS, Ormsbee 3rd HS. Lower esophageal sphincter relaxation is associated with increased cyclic nucleotide content. Am J Physiol. 1986;251:G786–93.

    PubMed  CAS  Google Scholar 

  101. Dodds WJ, Stewart ET, Hodges D, Zboralske FF. Movement of the feline esophagus associated with respiration and peristalsis. An evaluation using tantalum markers. J Clin Invest. 1973;52:1–13.

    Article  PubMed  CAS  Google Scholar 

  102. Paterson WG. Studies on opossum esophageal longitudinal muscle function. Can J Physiol Pharmacol. 1997;75:65–73.

    Article  PubMed  CAS  Google Scholar 

  103. Dent J. A new technique for continuous sphincter pressure measurement. Gastroenterology. 1976;71:263–7.

    PubMed  CAS  Google Scholar 

  104. Dogan I, Bhargava V, Liu J, Mittal RK. Axial stretch: A novel mechanism of the lower esophageal sphincter relaxation. Am J Physiol Gastrointest Liver Physiol. 2007;292:G329–34.

    Article  PubMed  CAS  Google Scholar 

  105. Jiang Y, Sandler B, Bhargava V, Mittal RK. Antireflux action of nissen fundoplication and stretch-sensitive mechanism of lower esophageal sphincter relaxation. Gastroenterology. 2010;140:442–9.

    Article  PubMed  Google Scholar 

  106. De Troyer A, Rosso J. Reflex inhibition of the diaphragm by esophageal afferents. Neurosci Lett. 1982;30:43–6.

    Article  PubMed  Google Scholar 

  107. Pickering M, Jones JF. The diaphragm: two physiological muscles in one. J Anat. 2002;201:305–12.

    Article  PubMed  Google Scholar 

  108. Fournier M, Sieck GC. Somatotopy in the segmental innervation of the cat diaphragm. J Appl Physiol. 1988;64:291–8.

    Article  PubMed  CAS  Google Scholar 

  109. Hammond CG, Gordon DC, Fisher JT, Richmond FJ. Motor unit territories supplied by primary branches of the phrenic nerve. J Appl Physiol. 1989;66:61–71.

    Article  PubMed  CAS  Google Scholar 

  110. Young RL, Page AJ, Cooper NJ, Frisby CL, Blackshaw LA. Sensory and motor innervation of the crural diaphragm by the vagus nerves. Gastroenterology. 2010;138:1091–101. e1-5.

    Article  PubMed  Google Scholar 

  111. Niedringhaus M, Jackson PG, Evans SR, Verbalis JG, Gillis RA, Sahibzada N. Dorsal motor nucleus of the vagus: a site for evoking simultaneous changes in crural diaphragm activity, lower esophageal sphincter pressure, and fundus tone. Am J Physiol Regul Integr Comp Physiol. 2008;294:R121–31.

    Article  PubMed  CAS  Google Scholar 

  112. Niedringhaus M, Jackson PG, Pearson R, Shi M, Dretchen K, Gillis RA, Sahibzada N. Brainstem sites controlling the lower esophageal sphincter and crural diaphragm in the ferret: a neuroanatomical study. Auton Neurosci. 2008;144:50–60.

    Article  PubMed  Google Scholar 

  113. Mittal RK, Rochester DF, McCallum RW. Electrical and mechanical activity in the human lower esophageal sphincter during diaphragmatic contraction. J Clin Invest. 1988;81:1182–9.

    Article  PubMed  CAS  Google Scholar 

  114. Sivri B, Mittal RK. Reverse-perfused sleeve: an improved device for measurement of sphincteric function of the crural diaphragm. Gastroenterology. 1991;101:962–9.

    PubMed  CAS  Google Scholar 

  115. Klein WA, Parkman HP, Dempsey DT, Fisher RS. Sphincter like thoracoabdominal high pressure zone after esophagogastrectomy. Gastroenterology. 1993;105:1362–9.

    Article  PubMed  CAS  Google Scholar 

  116. Altschuler SM, Boyle JT, Nixon TE, Pack AI, Cohen S. Simultaneous reflex inhibition of lower esophageal sphincter and crural diaphragm in cats. Am J Physiol. 1985;249:G586–91.

    PubMed  CAS  Google Scholar 

  117. Mittal RK, Fisher MJ. Electrical and mechanical inhibition of the crural diaphragm during transient relaxation of the lower esophageal sphincter. Gastroenterology. 1990;99:1265–8.

    PubMed  CAS  Google Scholar 

  118. Altschuler SM, Davies RO, Pack AI. Role of medullary inspiratory neurones in the control of the ­diaphragm during oesophageal stimulation in cats. J Physiol. 1987;391:289–98.

    PubMed  CAS  Google Scholar 

  119. Liu J, Yamamoto Y, Schirmer BD, Ross RA, Mittal RK. Evidence for a peripheral mechanism of esophagocrural diaphragm inhibitory reflex in cats. Am J Physiol Gastrointest Liver Physiol. 2000;278:G281–8.

    PubMed  CAS  Google Scholar 

  120. Liu J, Puckett JL, Takeda T, Jung HY, Mittal RK. Crural diaphragm inhibition during esophageal distension correlates with contraction of the esophageal longitudinal muscle in cats. Am J Physiol Gastrointest Liver Physiol. 2005;288:G927–32.

    Article  PubMed  CAS  Google Scholar 

  121. Sifrim D, Janssens J, Vantrappen G. Transient lower esophageal sphincter relaxations and esophageal body muscular contractile response in normal humans. Gastroenterology. 1996;110:659–68.

    Article  PubMed  CAS  Google Scholar 

  122. Holloway RH, Penagini R, Ireland AC. Criteria for objective definition of transient lower esophageal sphincter relaxation. Am J Physiol. 1995;268:G128–33.

    PubMed  CAS  Google Scholar 

  123. Steven C, Seller AF. Rumination. Washington, DC: American Physiological Society; 1968.

    Google Scholar 

  124. Kahrilas PJ, Dodds WJ, Dent J, Wyman JB, Hogan WJ, Arndorfer RC. Upper esophageal sphincter function during belching. Gastroenterology. 1986;91:133–40.

    PubMed  CAS  Google Scholar 

  125. Babaei A, Bhargava V, Mittal RK. Upper esophageal sphincter during transient lower esophageal sphincter relaxation: effects of reflux content and posture. Am J Physiol Gastrointest Liver Physiol. 2010;298:G601–7.

    Article  PubMed  CAS  Google Scholar 

  126. Babaei A, Bhargava V, Korsapati H, Zheng WH, Mittal RK. A unique longitudinal muscle contraction pattern associated with transient lower esophageal sphincter relaxation. Gastroenterology. 2008;134:1322–31.

    Article  PubMed  Google Scholar 

  127. Mittal RK, Padda B, Bhalla V, Bhargava V, Liu J. Synchrony between circular and longitudinal muscle contractions during peristalsis in normal subjects. Am J Physiol Gastrointest Liver Physiol. 2006;290:G431–8.

    Article  PubMed  CAS  Google Scholar 

  128. Dent J, Dodds WJ, Friedman RH, Sekiguchi T, Hogan WJ, Arndorfer RC, Petrie DJ. Mechanism of gastroesophageal reflux in recumbent asymptomatic human subjects. J Clin Invest. 1980;65:256–67.

    Article  PubMed  CAS  Google Scholar 

  129. Freidin N, Fisher MJ, Taylor W, Boyd D, Surratt P, McCallum RW, Mittal RK. Sleep and nocturnal acid reflux in normal subjects and patients with reflux oesophagitis. Gut. 1991;32:1275–9.

    Article  PubMed  CAS  Google Scholar 

  130. Cox MR, Martin CJ, Dent J, Westmore M. Effect of general anaesthesia on transient lower oesophageal sphincter relaxations in the dog. Aust N Z J Surg. 1988;58:825–30.

    Article  PubMed  CAS  Google Scholar 

  131. Little AF, Cox MR, Martin CJ, Dent J, Franzi SJ, Lavelle R. Influence of posture on transient lower oesophageal sphincter relaxation and gastro-oesophageal reflux in the dog. J Gastroenterol Hepatol. 1989;4:49–54.

    Article  PubMed  CAS  Google Scholar 

  132. Freidin N, Mittal RK, McCallum RW. Does body posture affect the incidence and mechanism of gastro-oesophageal reflux? Gut. 1991;32:133–6.

    Article  PubMed  CAS  Google Scholar 

  133. Holloway RH, Hongo M, Berger K, McCallum RW. Gastric distention: a mechanism for postprandial gastroesophageal reflux. Gastroenterology. 1985;89:779–84.

    PubMed  CAS  Google Scholar 

  134. Holloway RH, Wyman JB, Dent J. Failure of transient lower oesophageal sphincter relaxation in response to gastric distension in patients with achalasia: evidence for neural mediation of transient lower oesophageal sphincter relaxations. Gut. 1989;30:762–7.

    Article  PubMed  CAS  Google Scholar 

  135. Franzi SJ, Martin CJ, Cox MR, Dent J. Response of canine lower esophageal sphincter to gastric distension. Am J Physiol. 1990;259:G380–5.

    PubMed  CAS  Google Scholar 

  136. Penagini R, Carmagnola S, Cantu P, Allocca M, Bianchi PA. Mechanoreceptors of the proximal stomach: Role in triggering transient lower esophageal sphincter relaxation. Gastroenterology. 2004;126:49–56.

    Article  PubMed  Google Scholar 

  137. Strombeck DR, Harrold D, Ferrier W. Eructation of gas through the gastroesophageal sphincter before and after truncal vagotomy in dogs. Am J Vet Res. 1987;48:207–10.

    PubMed  CAS  Google Scholar 

  138. Martin CJ, Patrikios J, Dent J. Abolition of gas reflux and transient lower esophageal sphincter relaxation by vagal blockade in the dog. Gastroenterology. 1986;91:890–6.

    PubMed  CAS  Google Scholar 

  139. Mittal RK, Stewart WR, Schirmer BD. Effect of a catheter in the pharynx on the frequency of transient lower esophageal sphincter relaxations. Gastroenterology. 1992;103:1236–40.

    PubMed  CAS  Google Scholar 

  140. Paterson WG, Rattan S, Goyal RK. Experimental induction of isolated lower esophageal sphincter relaxation in anesthetized opossums. J Clin Invest. 1986;77:1187–93.

    Article  PubMed  CAS  Google Scholar 

  141. Trifan A, Shaker R, Ren J, Mittal RK, Saeian K, Dua K, Kusano M. Inhibition of resting lower esophageal sphincter pressure by pharyngeal water stimulation in humans. Gastroenterology. 1995;108:441–6.

    Article  PubMed  CAS  Google Scholar 

  142. Mittal RK, Chiareli C, Liu J, Shaker R. Characteristics of lower esophageal sphincter relaxation induced by pharyngeal stimulation with minute amounts of water. Gastroenterology. 1996;111:378–84.

    Article  PubMed  CAS  Google Scholar 

  143. Mittal RK, Holloway RH, Penagini R, Blackshaw LA, Dent J. Transient lower esophageal sphincter relaxation. Gastroenterology. 1995;109:601–10.

    Article  PubMed  CAS  Google Scholar 

  144. Lehmann A, Antonsson M, Bremner-Danielsen M, Flardh M, Hansson-Branden L, Karrberg L. Activation of the GABA(B) receptor inhibits transient lower esophageal sphincter relaxations in dogs. Gastroenterology. 1999;117:1147–54.

    Article  PubMed  CAS  Google Scholar 

  145. Blackshaw LA, Staunton E, Lehmann A, Dent J. Inhibition of transient LES relaxations and reflux in ferrets by GABA receptor agonists. Am J Physiol. 1999;277:G867–74.

    PubMed  CAS  Google Scholar 

  146. Zhang Q, Lehmann A, Rigda R, Dent J, Holloway RH. Control of transient lower oesophageal sphincter relaxations and reflux by the GABA(B) agonist baclofen in patients with gastro-oesophageal reflux disease. Gut. 2002;50:19–24.

    Article  PubMed  CAS  Google Scholar 

  147. Mittal RK, Holloway R, Dent J. Effect of atropine on the frequency of reflux and transient lower esophageal sphincter relaxation in normal subjects. Gastroenterology. 1995;109:1547–54.

    Article  PubMed  CAS  Google Scholar 

  148. Fang JC, Sarosiek I, Yamamoto Y, Liu J, Mittal RK. Cholinergic blockade inhibits gastro-oesophageal reflux and transient lower oesophageal sphincter relaxation through a central mechanism. Gut. 1999;44:603–7.

    Article  PubMed  CAS  Google Scholar 

  149. Boulant J, Fioramonti J, Dapoigny M, Bommelaer G, Bueno L. Cholecystokinin and nitric oxide in transient lower esophageal sphincter relaxation to gastric distention in dogs. Gastroenterology. 1994;107:1059–66.

    PubMed  CAS  Google Scholar 

  150. Penagini R, Bianchi PA. Effect of morphine on gastroesophageal reflux and transient lower esophageal sphincter relaxation. Gastroenterology. 1997;113:409–14.

    Article  PubMed  CAS  Google Scholar 

  151. Frisby CL, Mattsson JP, Jensen JM, Lehmann A, Dent J, Blackshaw LA. Inhibition of transient lower esophageal sphincter relaxation and gastroesophageal reflux by metabotropic glutamate receptor ligands. Gastroenterology. 2005;129:995–1004.

    Article  PubMed  CAS  Google Scholar 

  152. Lehmann A, Blackshaw LA, Branden L, Carlsson A, Jensen J, Nygren E, Smid SD. Cannabinoid receptor agonism inhibits transient lower esophageal sphincter relaxations and reflux in dogs. Gastroenterology. 2002;123:1129–34.

    Article  PubMed  CAS  Google Scholar 

  153. Lehmann A. Es0-hageal Pain. San Diego, CA: Plural Publishing; 2009.

    Google Scholar 

  154. Jenkinson AD, Scott SM, Yazaki E, Fusai G, Walker SM, Kadirkamanathan SS, Evans DF. Compliance measurement of lower esophageal sphincter and esophageal body in achalasia and gastroesophageal reflux disease. Dig Dis Sci. 2001;46:1937–42.

    Article  PubMed  CAS  Google Scholar 

  155. Liu J, Takeda T, Dogan I, Bhargava V, Mittal RK. Oesophago-gastric junction opening function: assessment using ultrasound imaging and the effects of atropine. Neurogastroenterol Motil. 2006;18:376–84.

    Article  PubMed  CAS  Google Scholar 

  156. McMahon BP, Frokjaer JB, Kunwald P, Liao D, Funch-Jensen P, Drewes AM, Gregersen H. The functional lumen imaging probe (FLIP) for evaluation of the esophagogastric junction. Am J Physiol Gastrointest Liver Physiol. 2007;292:G377–84.

    Article  PubMed  CAS  Google Scholar 

  157. Kwiatek MA, Hirano I, Kahrilas PJ, Rothe J, Luger D, Pandolfino JE. Mechanical properties of the esophagus in eosinophilic esophagitis. Gastroenterology. 2010;140:82–90.

    Article  PubMed  Google Scholar 

  158. Pandolfino JE, Shi G, Trueworthy B, Kahrilas PJ. Esophagogastric junction opening during relaxation distinguishes nonhernia reflux patients, hernia patients, and normal subjects. Gastroenterology. 2003;125:1018–24.

    Article  PubMed  Google Scholar 

  159. Pandolfino JE, Shi G, Curry J, Joehl RJ, Brasseur JG, Kahrilas PJ. Esophagogastric junction distensibility: a factor contributing to sphincter incompetence. Am J Physiol Gastrointest Liver Physiol. 2002;282:G1052–8.

    PubMed  CAS  Google Scholar 

  160. Katz PO, Richter JE, Cowan R, Castell DO. Apparent complete lower esophageal sphincter relaxation in achalasia. Gastroenterology. 1986;90:978–83.

    PubMed  CAS  Google Scholar 

  161. Mearin F, Malagelada JR. Complete lower esophageal sphincter relaxation observed in some achalasia patients is functionally inadequate. Am J Physiol Gastrointest Liver Physiol. 2000;278:G376–83.

    PubMed  CAS  Google Scholar 

  162. Blom D, Bajaj S, Liu J, Hofmann C, Rittmann T, Derksen T, Shaker R. Laparoscopic Nissen fundoplication decreases gastroesophageal junction distensibility in patients with gastroesophageal reflux disease. J Gastrointest Surg. 2005;9:1318–25.

    Article  PubMed  Google Scholar 

  163. Kwiatek MA, Kahrilas K, Soper NJ, Bulsiewicz WJ, McMahon BP, Gregersen H, Pandolfino JE. Esophagogastric junction distensibility after fundoplication assessed with a novel functional luminal imaging probe. J Gastrointest Surg. 2010;14:268–76.

    Article  PubMed  Google Scholar 

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Acknowledgment

Grant Support: NIH-RO1-DK060733.

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  1. Department of Medicine, University of California San Diego & San Diego VA Health Care Center, San Diego, CA, USA

    Ravinder Mittal MD

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  1. Ravinder Mittal MD
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Editors and Affiliations

  1. Div. Gastroenterology & Hepatology, Medical College of Wisconsin, West Wisconsin Avenue 9200, Milwaukee, 53226, Wisconsin, USA

    Reza Shaker

  2. , Dpt Otolaryngology/Head & Neck Surg., UC Davis Medical Center, Stockton Blvd. 2521, Sacramento, 95817, California, USA

    Peter C. Belafsky

  3. Ctr for Voice, Airway & Swallowing Disor, Department of Otolaryngology, Georgia Health Sciences University, 15th Street 1120, Augusta, 30912, Georgia, USA

    Gregory N. Postma

  4. , Dpt of Communication Sciences & Disorder, University of Wisconsin-Milwaukee, East Hartford Ave 2400, Milwaukee, 53201, Wisconsin, USA

    Caryn Easterling

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Mittal, R. (2013). Sphincter Mechanisms at the Esophago-Gastric Junction. In: Shaker, R., Belafsky, P., Postma, G., Easterling, C. (eds) Principles of Deglutition. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3794-9_23

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