THE HIGH PRESSURE ZONE OF THE DISTAL ESOPHAGUS

描述(申请人摘要)：PI的假设是脚 横隔膜与固有的食道下括约肌相互作用 举止复杂。这些相互作用有两种形式：1)时空相互作用 其中，脚横隔肌和固有下食道括约肌(LES) 在空间和时间上彼此错开；以及2)机械 在相互作用中，LES和CD的每个组件对 胃食道交界处高压区产生的压力(GEJHPZ) 单独的和组合的。当两者中的任何一个出现异常时 在GEJHPZ回流事件和流体逆流时的这些相互作用 将会发生。这项建议的目的是确定相对的 内源性LES和CD在抗反流中的生理学作用 GEJHPZ的障碍。PI计划将CD的相对运动定义为 内在性使CD的松弛和收缩与 LES、Cd对远端食道的压迫作用和作用力， Cd在液体顺行中的作用及Cd在液体顺行运动中的作用 GEJHPZ的诱导松弛和液体的逆行运动 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 (功能)。为了实现这些具体目标，PI计划：1)确定 呼吸对腰椎位置和压力关系的影响 作为GEJHPZ的组成部分的本征LES和Cd。调查人员的假设是 这种呼吸引起脚横隔膜相对于 并因此影响这两者的解剖关系。 2)将固有的LE与脚分离 使用生理和药物手法的横隔膜。压力计 Cd对GEJHPZ的贡献将通过药理学来确定 以及增强、减弱甚至消融这些影响的生理动作 为了更好地确定裁谈会对全球气候变化框架的贡献： 3)确定吞咽过程中食道缩短对 抗反流屏障GEJHPZ。这将通过量化，相对的 固有的LES和CD彼此之间的位移，响应于 吞咽不同剂量的水时，食道缩短；以及 4)利用CEJHPZ的结构和功能是 扭曲了对LES和CD相对作用的研究。这些条件 包括裂孔疝气(LES移位)；Nissen胃底折叠术 (强化的HPZ)之前切除胃食道交界处(失去 内源性LES)；伴和不伴低血压LES的GERD。目的5研究 GEJHPZ松弛对GEJHPZ逆流的影响 并引发回流事件。这将通过膨胀液体来实现。 用充气气球填胃，或用食道扩张 充气气囊松弛GEJHPZ并诱导其逆行 体液从胃到食道的运动在正常对照和 伴和不伴低血压LES的GERD患者。他们将描绘出这两个 LES与CD的正常和异常相互作用 超声和测压，以确定生理学和病理生理学 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.