GASTROINTESTIONAL MOTOR EFFECTS OF IONIZING RADIATION

放射治疗是治疗癌症的一种主要方法。然而， 随着这一技术的应用和效果的提高，人们对 正常的组织毒性。用于治疗腹部和盆腔肿瘤， 肠道耐受性往往是一个主要的限制因素。最近来自 我们的实验室(1，17)和其他实验室(9，10，16，18)已经证明 小肠的运动活动发生了戏剧性的变化 在分次或单次亚致死剂量的电离辐射之后。 这些变化中的许多可能与患者的症状直接相关 接受放射治疗。这项研究的主要目标是 因此，建议是1)扩大我们之前关于以下影响的工作 小肠至结肠的分次照射剂量，2) 为了描述肌源性神经和化学机制可能是 负责术后小肠运动活动的变化 辐射，以及3)将动物研究扩展到人体模型。 在犬模型中，将进行收缩和肌电记录 分别采用应变片传感器和双极电极。 这些装置将通过无菌外科手术植入动物体内 技巧。胆汁在异常收缩产生中的作用 放射计划期间的模式将通过分流胆汁来研究 通过在清醒状态下植入外置式硅胶导管 10天的恢复期。来自人类结肠的录音和小的 肠子将用测压方法制成。数据的分析将是 通过视觉和我们实验室开发的计算机方法完成。 我们的最终目标是描述产生异常运动的机制。 在人类放射治疗过程中的模式。对这些问题的认识 机制将有助于提出适当的药理学试剂， 可能会阻止这些影响，并提高人类对辐射暴露的耐受性。

Radiation therapy is a major modality in the treatment of cancer. However, as the application and efficacy of this increased, so has the concern for normal tissue toxicity. For the treatment of abdominal and pelvic tumors, intestinal tolerance is often a major limiting factor. Recent studies from our lab (1, 17) and other laboratories (9, 10, 16, 18) have demonstrated that dramatic changes occur in the small intestinal motor activity following fractionated or single sub-lethal doses of ionizing radiation. Many of these changes may have a direct symptomatic relevance to patients receiving radiation therapy. the primary objectives of this research proposal, therefore, are 1) to expand our previous work on the effects of fractionated doses of irradiation on the small intestine to the colon, 2) to delineate the myogenic neural and chemical mechanisms that may be responsible for the changes in small intestinal motor activity after radiation, and 3) to extend the animal studies to the human model. In the canine model, the contractile and myoelectric recording will be made by using strain gauge transducer and bipolar electrodes, respectively. These devices will be implanted in the animal using sterile surgical techniques. The role of bile in the production of abnormal contractile patterns during radiation schedule will be studied by diverting the bile through exteriorized silastic catheters implanted in conscious state after a 10 day recovery period. The recordings from the human colon and small intestine will be made by manometric methods. The analysis of data will be done visually and by computer methods developed in our laboratory. Our ultimate aim is to delineate the mechanisms that produce abnormal motor patterns during radiation therapy in humans. The understanding for these mechanisms would help in proposing appropriate pharmacologic agents that may block these effects and improve human tolerance to radiation exposure.