PERIPHERAL MECHANISMS OF ESOPHAGEAL PERISTALSIS

先前的研究表明，存在神经肌肉机制。 在食道平滑肌段的壁内部分 这可能是环状中看到的蠕动事件的原因 以及吞咽过程中的纵向肌层。整体而言 这项建议的目的是在药理学上表征 食道纵行和环行的壁内神经支配 肌肉层次，并确定这一特定组成部分的作用 神经支配在食道蠕动的外周机制中起作用。 具体地说，这项提议涉及在体外和体内使用 环状和纵向食道平滑肌的研究技术 对神经刺激作出反应的收缩。体外研究将 涉及对食道肌条和体内的跨壁刺激 研究将涉及迷走神经刺激或吞咽诱导的肌肉 宫缩。不同的拮抗剂和激动剂对这些细胞的影响 将测定神经介导的肌肉收缩，以识别 神经支配的各个组成部分。 这些研究的结果将使我们更好地了解 参与食道蠕动的壁内神经肌肉机制。 这应该会增加对糖尿病的病理生理学的理解。 食道疾病和这类疾病更合理的治疗方法 如弥漫性食道痉挛和失弛缓症。 在拉杰·K·戈亚尔博士的赞助下，候选人是获奖者 个人国家研究服务奖，以研究外围设备 食道蠕动的机制。这项工作已经产生了几个 关于食道蠕动的重要出版物。这位候选人在 本提案希望将这些研究扩大到关于 食道蠕动的机制随着他逐渐成为一名 独立调查员。 赞助商拉杰·K·戈亚尔博士是哈佛医学院的医学教授 他是贝丝以色列医院的消化科主任，也是一名 公认的胃肠动力领域的领导者。戈亚尔医生的 赞助，以及贝丝以色列医院的周围调查人员 哈佛医学院应该提供一个良好的环境 应聘者的学习和发展。

Prior investigations have shown that a neuromuscular mechanism exists within the intramural portion of the smooth muscle segment of the esophagus which may be responsible for the peristaltic events seen in the circular and longitudinal muscle layers during the act of swallowing. The overall objective of this proposal is to pharmacologically characterize the intramural innervation of esophageal longitudinal and circular smooth muscle layers and determine what roles specific components of this innervation play in the peripheral mechanism of esophageal peristalsis. Specifically, this proposal involves the use of in vitro and in vivo techniques to study circular and longitudinal esophageal smooth muscle contractions in response to nerve stimulation. In vitro studies will involve transmural stimulation of esophageal muscle strips and in vivo studies will involve vagal stimulation or swallow-induced muscle contractions. The effects of various antagonists and agonists on these nerve-mediated muscle contractions will be determined so as to identify the various components of innervation. The results of these studies will provide a better understanding of the intramural neuromuscular mechanism involved in esophageal peristalsis. This should lead to an increased understanding of the pathophysiology of esophagel disorders and perhaps a more rational therapy for such disorders as diffuse esophageal spasm and achalasia. The candidate, under the sponsorship of Dr. Raj K. Goyal, was the recipient of an individual National Research Service Award to study the peripheral mechanisms of esophageal peristalsis. This work has resulted in several important publications concerning esophageal peristalsis. The candidate in the present proposal wishes to extend these studies concerning the mechanisms of esophageal peristalsis as he progresses toward becoming an independent investigator. The sponsor, Dr. Raj K. Goyal, is Professor of Medicine at Harvard Medical School and Chief of Gastroenterology at Beth Israel Hospital and is an acknowledged leader in the area of gastrointestinal motility. Dr. Goyal's sponsorship, as well as surrounding investigators at Beth Israel Hospital and Harvard Medical School should provide an excellent environment for the candidate's studies and development.