The Physiology of the Pharyngo-Esophageal Junction

咽食管连接处的生理学

基本信息

  • 批准号:
    9116200
  • 负责人:
  • 金额:
    $ 28.99万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2007
  • 资助国家:
    美国
  • 起止时间:
    2007-09-15 至
  • 项目状态:
    未结题

项目摘要

Gastroesophageal reflux disease (GERD) occurs as either esophageal-GERD (E-GERD) or supraesophageal- GERD (SE-GERD). The primary cause of E-GERD is inappropriate gastro-esophageal reflux (GER), but the primary cause of SE-GERD is inappropriate gastro-esophago-pharyngeal reflux (GEPR). While there has been much investigation of the mechanisms of GER very little is known about the mechanisms of esophago- pharyngeal reflux (EPR). The aim of this project is to determine the physiology of reflexes associated with flow across the pharyngo-esophageal junction (PEJ). We address a number of important observations in humans related to the physiology and pathophysiology of the PEJ. It has been observed that transient relaxation of the upper esophageal sphincter (TUESR) occurs with transient relaxation of the lower esophageal sphincter (TLESR), but the mechanism of this relationship is unknown. We will define the relationship between these reflexes. Distension of the esophagus causes the UES to expand to include the adjacent esophagus, but the full extent of this response and mechanism of its initiation are unknown. We will fully characterize this response and determine its neural mechanisms. In some patients with SE-GERD, the contractile response of the UES to infusion of fluid into the esophagus sometimes rapidly and briefly gives way to allow EPR, but the mechanisms of this effect are unknown. We will test the hypothesis that this rapid brief relaxation of the UES is due to activation of the esophago-UES relaxation reflex (EURR) that inhibits the esophago-UES contractile reflex (EUCR). In addition, we will determine the location along the length of the esophagus of the receptors that activate EURR. Although the neural control of GER has received much attention, the peripheral and central mechanisms of EPR are largely unknown. A newly appreciated innervation important to the function of the PEJ is the SLN afferents from the proximal cervical esophagus, but the function of these afferents is largely unknown. We will fully investigate the role of these afferents in the control of reflexes associated with anterograde and retrograde flow across the PEJ. Many of the central nervous system nuclei controlling aspects of GER, e.g. TLESR, have been identified but the central nervous system control of EPR is largely unknown. Therefore, we will investigate the role of the brainstem in controlling both EPR and GEPR. These studies will provide a firm scientific basis for defining the physiology of reflexes controlling anterograde and retrograde flow across the PEJ. RELEVANCE (See instructions): GERD affects 10% of the US population. The primary cause of E-GERD is inappropriate GER, but the primary cause of SE-GERD is inappropriate EPR. While there has been much investigation of the mechanisms of GER, very little is known about the mechanisms of EPR. The primary barrier to EPR is the PEJ, and these studies are designed to investigate the physiology of the PEJ.
胃食管反流病 (GERD) 以食管胃食管反流病 (E-GERD) 或食管上胃食管反流病的形式发生。 胃食管反流病(SE-GERD)。 E-GERD 的主要原因是不适当的胃食管反流 (GER),但 SE-GERD 的主要原因是不适当的胃食管咽反流 (GEPR)。虽然有 对 GER 机制进行了大量研究,但对食管癌的机制知之甚少。 咽反流(EPR)。该项目的目的是确定与 流过咽食管交界处(PEJ)。我们讨论了一些重要的观察结果 人类与 PEJ 的生理学和病理生理学相关。据观察,瞬态 上食管括约肌 (TUESR) 的松弛伴随下食管括约肌的短暂松弛而发生。 食管括约肌(TLESR),但这种关系的机制尚不清楚。我们将定义 这些反射之间的关系。食管扩张导致 UES 扩张以包括 邻近的食道,但这种反应的全部范围及其引发机制尚不清楚。我们将 充分表征这种反应并确定其神经机制。在一些 SE-GERD 患者中, UES 对食管内液体输注的收缩反应有时会快速而短暂地给出 允许 EPR 的方式,但这种效果的机制尚不清楚。我们将检验这种快速的假设 UES 的短暂松弛是由于食管-UES 松弛反射 (EURR) 的激活,该反射抑制 食管-UES 收缩反射 (EUCR)。此外,我们将确定沿长度的位置 食道中存在激活 EURR 的受体。尽管 GER 的神经控制受到了很多关注 值得注意的是,EPR 的外周和中枢机制在很大程度上尚不清楚。新欣赏的 对 PEJ 功能很重要的神经支配是来自近端颈段食管的 SLN 传入神经, 但这些传入神经的功能很大程度上是未知的。我们将充分研究这些传入神经的作用 与穿过 PEJ 的顺行和逆行血流相关的反射的控制。许多中央 神经系统核控制 GER 的各个方面,例如TLESR,已被鉴定,但中枢神经 EPR 的系统控制在很大程度上是未知的。因此,我们将研究脑干在 控制 EPR 和 GEPR。这些研究将为定义生理学提供坚实的科学基础 控制穿过 PEJ 的顺行和逆行血流的反射。 相关性(参见说明): GERD 影响 10% 的美国人口。 E-GERD 的主要原因是 GER 不当,但 SE-GERD 的主要原因是 EPR 不当。虽然对此进行了大量调查 GER 的机制,而对于 EPR 的机制知之甚少。 EPR 的主要障碍是 PEJ,这些研究旨在研究 PEJ 的生理学。

项目成果

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IVAN M LANG其他文献

IVAN M LANG的其他文献

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{{ truncateString('IVAN M LANG', 18)}}的其他基金

The Physiology of the Pharyngo-Esophageal Junction
咽食管连接处的生理学
  • 批准号:
    9306057
  • 财政年份:
    2007
  • 资助金额:
    $ 28.99万
  • 项目类别:
The Physiology of the Pharyngo-Esophageal Junction
咽食管连接处的生理学
  • 批准号:
    8742111
  • 财政年份:
    2007
  • 资助金额:
    $ 28.99万
  • 项目类别:
AIRWAY PROTECTION DURING VOMITING
呕吐期间的气道保护
  • 批准号:
    6571531
  • 财政年份:
    2002
  • 资助金额:
    $ 28.99万
  • 项目类别:
AIRWAY PROTECTION DURING VOMITING
呕吐期间的气道保护
  • 批准号:
    6442942
  • 财政年份:
    2001
  • 资助金额:
    $ 28.99万
  • 项目类别:
AIRWAY PROTECTION DURING VOMITING
呕吐期间的气道保护
  • 批准号:
    6300844
  • 财政年份:
    2000
  • 资助金额:
    $ 28.99万
  • 项目类别:
AIRWAY PROTECTION DURING VOMITING
呕吐期间的气道保护
  • 批准号:
    6210287
  • 财政年份:
    1999
  • 资助金额:
    $ 28.99万
  • 项目类别:

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