THE HIGH PRESSURE ZONE OF THE DISTAL ESOPHAGUS

描述（申请人摘要）：PI的假设是脚 横膈膜与固有的食管下括约肌相互作用， 复杂的方式。这些相互作用有两种形式：1）时空相互作用 其中腿隔膜和固有下食管括约肌（LES） 在空间和时间上都相互位移; 2）机械的 相互作用，其中LES和CD的每个组分都有助于 胃食管交界处高压区（GEJHPZ）产生的压力 单独地和组合地。当有任何异常， 这些相互作用，在GEJHPZ反流事件和液体逆行流动 会发生。本建议的目的是确定相对 内源性LES和CD在提供抗反流中的生理作用 在GEJHPZ的障碍。PI计划定义CD的相对运动， 内在LES与CD的松弛和收缩有关， LES，CD对远端食管的压缩效应和力， CD在液体顺行运动中的作用和CD在 引起的GEJHPZ的松弛和液体从 胃到食道同时进行高分辨率超声和测压 将用于将解剖位置（结构）与压力相关联 （函数）。为了实现这些具体目标，PI计划：1）确定 呼吸作用对肺动脉位置和压力关系的影响 内在LES和CD作为GEJHPZ的组成部分。研究人员假设 呼吸导致脚隔膜相对于 内在LES，因此，影响这两者的解剖关系 2）将固有LES与脚分离 隔膜使用生理和药理操作。测压 CD对GEJHPZ的贡献将通过使用药理学 和生理上的操作来加强、减弱甚至消除这些影响 为了更好地确定裁谈会对通用电气、JHPZ的贡献： 3)确定吞咽过程中食管缩短对 抗回流屏障GEJHPZ。这将通过定量，相对 内在LES和CD相互位移，响应于 食道缩短，在吞咽各种推注体积的水期间;以及 4)利用几个条件，其中CEJHPZ的结构和功能是 扭曲的研究LES和CD的相对作用。这些条件 包括食管裂孔疝（LES移位）;尼森胃底折叠术 （加强HPZ）胃食管连接部切除术前（ （1）有无内分泌性LES;（2）有无内分泌性LES。目标5研究 通过诱导GEJHPZ松弛在GEJHPZ处的逆行流动的影响 并引发反流事件。这将通过使流体膨胀来实现 用充气气囊填充胃，或用气囊扩张食道。 充气球囊，以诱导GEJHPZ松弛并引起逆行 在正常对照组中，液体从胃运动到食管， 伴有和不伴有膨胀性LES的GERD患者。他们将描绘出 LES和CD的正常和异常相互作用，同时使用 超声和测压，以确定的生理和病理生理的 GEJHPZ。

DESCRIPTION (Applicant's Abstract): The PI's hypothesis is that the crural diaphragm interacts with the intrinsic lower esophageal sphincter in a very complex manner. These interactions take two forms: 1) space-time interactions in which the crural diaphragm and intrinsic lower esophageal sphincter (LES) are displaced from each other both in space and in time; and 2) mechanical interactions in which each component of the LES and CD contributes to the pressure generated at the gastroesophageal junction high-pressure zone (GEJHPZ) individually and in combination. When there are abnormalities in either of these interactions, at the GEJHPZ reflux events and retrograde flow of fluids will occur. The purpose of this proposal is to determine the relative physiologic roles of the intrinsic LES and CD in providing an anti-reflux barrier at the GEJHPZ. The PI plans to define the relative motion of the CD to the intrinsic LES the relaxation and contraction of the CD in relationship to the LES, the compressive effect and forces of the CD on the distal esophagus, the role of the CD in antegrade movement of liquids and the role of the CD in induced relaxation of the GEJHPZ and retrograde movement of liquids from the stomach to the esophagus. Simultaneous high-resolution ultrasound and manometry will be utilized to correlate anatomical position (structure) with pressure (function). To achieve these specific aims the PI plans to: 1) determine the effect of respiration on the position and pressure relationships of the intrinsic LES and CD as components of the GEJHPZ. The investigators hypothesize that respiration causes movement of the crural diaphragm relative to the intrinsic LES and, therefore, effects the anatomical relationship of these two structures to each other; 2) separate the intrinsic LES from the crural diaphragm using physiologic and pharmacologic manipulations. The manometric contribution of the CD to the GEJHPZ will be determined by using pharmacologic and physiologic maneuvers to strengthen, diminish and even ablate the effects of the CD in order to better define the contribution of the CD to the GEJHPZ: 3) determine the effect of esophageal shortening during swallowing on the antireflux barrier GEJHPZ. This will be done by quantitating, the relative displacement of the intrinsic LES and CD to each other, in response to esophageal shortening, during swallowing of various bolus volumes of water; and 4) utilize several conditions in which the CEJHPZ structure and function are distorted to study the relative roles of the LES and CD. These conditions include hiatal hernia (displacement of the LES); Nissen fundoplication (reinforced HPZ) prior resection of the gastroesophageal junction (loss of the intrinsic LES); and GERD with and without hypotensive LES. Aim 5 Study the effect of retrograde flow at the GEJHPZ by inducing relaxation of the GEJHPZ and eliciting reflux events. This will be achieved by distending the fluid filled stomach with an air filled balloon, or distending the esophagus with an air filled balloon to induce relaxation of the GEJHPZ and elicit retrograde fluid movement from the stomach to the esophagus in normal controls and patients with GERD with and without a hypotensive LES. They will delineate both the normal and abnormal interactions of the LES and CD, using simultaneous ultrasound and manometry to define the physiology and pathophysiology of the GEJHPZ.