CONTROL OF COLONIC MOTILITY IN HEALTH AND DISEASE

这项研究建议的总体目标是阐明 大鼠结肠运动的肌源性、神经和肽能调控 健康和疾病。在过去的几年里，我们已经定义了 迁移性和非迁移性运动复合体及其相互作用 犬结肠肌电相关(1，2)。我们还有 定义了狗的短期和长期收缩，并 人结肠(2-6)。我们现在的目标是确定1) 外源性和内源性神经对神经细胞启动和迁移的控制 结肠运动复合体，2)某些生理性的影响 高纤维和低纤维饮食等刺激对组织的影响 结肠运动复合体，3)液体负荷和直接作用的影响 泻药进入结肠对结肠运动的影响 活动，以及4)几个相关的活动地点 肠道神经系统中的多肽及其对血管生成的影响 结肠动力活动。 这些实验将在清醒和麻醉的狗身上进行。 运动和肌电活动将通过手术记录 植入式应变片传感器和双极电极 全身麻醉。外源性神经在脑血管紧张性瘫痪中的作用 结肠动力复合体将通过以下技术确定 神经切断术和多发性肌切开术切除内脏神经。这个 液体负荷和泻药对结肠动力活动的影响 在完整的结肠和孤立的结肠环路中进行研究。流体 泻药会被注入结肠的管腔。 留置硅胶导管。电和电之间的耦合 多肽的收缩活动和外周效应 通过近距离动脉内注射这些物质来研究 结肠的短节段。数据将通过以下方式进行分析 计算机和视觉方法。 我们的长期目标是应用知识和理解 从动物实验到人类结肠的研究 健康和各种病理状态下的运动功能，如 肠易激综合征，特发性假性肠梗阻 和憩室病。对正常运作的洞察 肌源性、神经性和化学性(包括多肽)控制 健康和结肠运动障碍的机制是必不可少的 提出适当的药理、治疗和手术建议 疾病患者结肠运动功能正常化的措施 提供一种症状缓解。

The overall objective of this research proposal is to elucidate the myogenic, neural and peptidergic control of colonic motility in health and disease. During the past few years we have defined the migrating and non-migrating motor complexes and their myoelectric correlates in the dog colon (1,2). We have also defined the short and long duration contractions in the dog and human colon (2-6). Our objectives now are to determine 1) the extrinsic and intrinsic neural control of initiation and migration of colonic motor complexes, 2) the effects of certain physiological stimuli such as high and low fiber diets on the organization of colonic motor complexes, 3) the effects of fluid load and direct administration of laxatives into the colon on colonic motor activity, and 4) the site of action of a few of the relevent peptides in the enteric nervous system and their effects on colonic motor activity. The experiments will be done on conscious and anesthetized dogs. Motor and myoelectric activities will be recorded by surgically implanted strain gage transducers and bipolar electrodes under general anesthesia. The role of extrinsic nerves in the control of colonic motor complexes will be determined by the technique of nerve section and of intrinsic nerves by multiple myotomies. The effects of fluid load and laxatives on colonic motor activity will be studied in the intact colon and in isolated colonic loops. Fluids and laxatives will be infused into the lumen of the colon through indwelling silastic catheters. The coupling between electrical and contractile activities and the peripheral effects of peptides will be studied by close-intraarterial injections of these substances in short segments of the colon. The data will be analysed by computer and visual methods. Our long term goal is to apply the knowledge and understanding obtained from animal experiments to the study of human colonic motor function in health and in various pathological states such as irritable bowel syndrome, idiopathic intestinal pseudo-obstruction and diverticular disease. An insight into the normal functioning of the myogenic, neural and chemical (including peptides) control mechanisms in health and colonic motor disorders is essential to propose appropriate pharmacologic, therapeutic and surgical measures to normalize colonic motor function in disease or to provide a symptomatic relief.