PHYSIOLOGY AND PATHOPHYSIOLOGY OF ESOPHAGEAL MOTILITY

本研究的主要目的是：（1）阐明 （a）食管扩张和（B）食管下括约肌生理学 (LES)（2）确定其性质; 神经递质参与食管反射活动;（3）探索 食管体和LES的药理学;（4）达到一个 通过补充这些结构-功能关系， 形态学研究。 这些动物实验 模型将扩展到手术中获得的病变组织， 食管疾病患者。 我们将使用许多不同的体内和体外系统来记录 间接（抽吸电极）和直接（单电极）膜电位 细胞内）的方法，以便了解神经的性质， 反射在两个完整的动物以及在肌肉条。 这些研究 也将延伸到肌间神经丛的形态和形态测量学， 使用我们最近开发的快速无银方法和我们的技术， 神经节隔离 免疫细胞化学方法将提供有价值的 组织生理学的见解，以补充形态学的发现。 神经节分离也将用于研究超微结构， 肌间神经丛的扫描和透射电子显微镜 食道的各个部分。 形态和生理 因此将进行食管功能的神经控制的相关性。 这些研究将促进我们对食管癌生理学的理解 运动和食管运动障碍的病理生理学。 这 理解可能为合理对待这些问题提供途径。 紊乱 此外，从这些食管研究中吸取的教训 可能在生理学和病理生理学的更广泛的影响， 自主神经系统，特别是胃肠道。

The major objectives of this research proposal are: (1) to elucidate the physiology of (a) esophageal peristalsis and (b) lower esophageal sphincter (LES) tone and relaxation; (2) to identify the nature of the neurotransmitters involved in esophageal reflex activities; (3) to explore the pharmacology of esophageal body and LES; and (4) to arrive at a synthesis of structure-function relationships by complementing these studies with morphological investigations. These studies in the animal model will be extended to diseased tissues obtained at surgery from patients with esophageal disorders. We will use a number of different in vivo and in vitro systems to record membrane potentials by indirect (suction electrodes) and direct (single cell intracellular) methods, so as to learn about the nature of the neural reflexes in both intact animals as well as in muscle strips. These studies will also extend to the morphology and morphometry of the myenteric plexus, using our recently-developed rapid non-silver method and our technique of ganglionic isolation. An immunocytochemical approach will provide valuable histophysiological insights to supplement morphological findings. Ganglionic isolation will also be used to investigate ultrastructure with scanning and transmission electron microscopy of the myenteric plexus from various segments of the esophagus. Morphologic and physiologic correlations of neural control of esophageal function will thus be made. These studies will advance our understading of the physiology of esophageal motility and the pathophysiology of esophageal motor disorders. This understanding may provide avenues for rational treatment of these disorders. Moreover, lessons learned from these studies of the esophagus may have wider implications in physiology and pathophysiology of the autonomic nervous system, particularly that of the gastrointestinal tract.