CONTROL OF COLONIC MOTILITY IN HEALTH AND DISEASE

本研究提案的总体目标是阐明 结肠运动的肌源性、神经性和肽能控制 健康和疾病。 在过去的几年里，我们定义了 迁移性和非迁移性运动复合体及其 犬结肠中的肌电相关性（1，2）。 我们还 定义了狗的短时间和长时间收缩， 人结肠（2-6）。 我们现在的目标是确定1） 启动和迁移的外在和内在神经控制 结肠运动复合体，2）某些生理的影响， 刺激，如高纤维和低纤维饮食的组织 结肠运动复合体，3）液体负荷和直接 结肠运动时结肠内给予泻药 活动，以及4）一些相关活动的活动场所 肽在肠神经系统中的作用 结肠运动活动 实验将在清醒和麻醉的狗身上进行。 将通过手术记录运动和肌电活动 植入式应变计传感器和双极电极 全麻 外源性神经在控制脑缺血中的作用 结肠运动复合体将通过以下技术确定： 神经切片和内在神经的多肌切开术。 的 液体负荷和泻药对结肠运动活动的影响将 在完整结肠和分离的结肠循环中进行研究。 流体 泻药将通过结肠腔注入 留置硅橡胶导管 电气和 收缩活动和肽的外周效应将 通过近动脉内注射这些物质进行研究， 结肠的短段。 数据将由 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癌的研究 运动功能在健康和各种病理状态， 肠易激综合征，特发性假性肠梗阻 和憩室病。 对正常功能的深入了解 生肌、神经和化学（包括肽）控制 健康和结肠运动障碍的机制是必不可少的， 提出适当的药理学、治疗学和手术学建议 使疾病中的结肠运动功能正常化的措施或 缓解症状

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.