FACTORS RESPONSIBLE FOR THE CONTROL OF HUMAN LABOR

该提案将阐明人类怀孕子宫如何协调 子宫肌细胞的功能与子宫收缩力有关。获得的知识 这项工作将确定负责协调的因素， 分娩的启动和维持。 这些问题都密切相关 与早产、过期妊娠和功能障碍有关 临产，与早产、胎儿窘迫直接相关 剖腹产率。 增进对子宫收缩力的了解 可能会允许治疗异常分娩 针对潜在的生理异常。 我们有 最近提出了一个假设的初始形式，该假设详细说明了如何 子宫细胞在人类劳动中进行交流。 该模型包含 全局（整个子宫）与局部机制。 的 该模型的本质是器官层面的沟通是通过行动 潜在的传播，但负责启动的信号 每个细胞的收缩是由细胞间钙波进行的。 因此，该假设被称为动作电位 - 钙波 假说（AP 波假说）。 本研究的目的是测试基础和配方 AP 波假说的结论，并在发现其缺点时对其进行修改 确定。 这一假设的演变形式有望允许 临床医生追踪分娩的具体临床参数（例如 子宫收缩的强度和频率）返回细胞 机制。 结果，特定的分娩异常（间隔不良） 宫缩、对催产素的异常反应、基线升高 压力等）然后就能够与 特定的细胞功能。 这些知识将提供 选择特定疗法的科学依据 特殊的产程异常。 我们提出了技术的组合（组织的结构研究， 共焦显微镜、电生理学和钙染料成像） 了解钙代谢和信号传递的目标 组织。 在这个项目结束时，我们将得到一个改进的 了解人类怀孕子宫的功能单位 为基础知识的教育、研究和应用提供基础 科学知识到临床医学。

This proposal will elucidate how the human pregnant uterus coordinates myometrial cell function with uterine contractility. Knowledge gained from this work will define the factors responsible for the coordination, initiation, and maintenance of labor. These issues are intimately associated with preterm labor, postdates pregnancy, and dysfunctional labor, which correlate directly with prematurity, fetal distress, and cesarean section rates. Improved understanding of uterine contractility will potentially allow treatments of an abnormality of labor to be directed towards the underlying physiological abnormality. We have recently developed the initial form of a hypothesis that specifies how the uterine cells communicate in human labor. This model incorporates global (throughout the entire uterus) with local mechanisms. The essence of this model is that organ-level communication is by action potential propagation, but the signal responsible for initiating contraction of each cell is carried by intercellular calcium waves. This hypothesis is therefore called the action potential - calcium wave hypothesis (AP-wave hypothesis). The purpose of this research is to test the foundation and formulation of the AP-wave hypothesis and to modify it when shortcomings are identified. The evolving form of this hypothesis will hopefully allow clinicians to trace specific clinical parameters of labor (such as strength and frequency of uterine contractions) back to cellular mechanisms. As a result, specific abnormalities of labor (poor spacing of contractions, abnormal response to oxytocin, elevated baseline pressure, and many others) would then be able to be correlated with specific cellular functions. This knowledge would provide the scientific basis for the selection of a particular therapy for a particular abnormality of labor. We propose a combination of techniques (structural studies of tissue, confocal microscopy, electrophysiology and calcium dye imaging) with a goal of understanding calcium metabolism and signal transmission through tissue. At the conclusion of this project we will have an improved understanding of the functional unit of the human pregnant uterus, which will provide the basis for education, research, and application of basic science knowledge to clinical medicine.